HIV infection in pregnant women: clinical guidelines

List of Abbreviations

ALT - alanine aminotransferase

ARV - antiretroviral drugs (according to the ATC classification: antivirals for systemic use)

ART - antiretroviral therapy

AST - aspartate aminotransferase

HIV - human immunodeficiency virus

IUI - intrauterine insemination

VL - viral load - number of copies of HIV RNA per 1 ml of biological substrate

WHO - World Health Organization

ART - assisted reproductive technologies

PrEP - pre-exposure prophylaxis

DM - dispensary monitoring

DNA - deoxyribonucleic acid

NTD - neural tube defect

GIT - gastrointestinal tract

WB - immunoblotting

INSTIs - HIV integrase strand transfer inhibitors (according to the ATC classification: integrase inhibitors)

ICSI - intracytoplasmic sperm injection

BMI – body mass index

PIs - HIV protease inhibitors (according to the ATC classification: protease inhibitors)

STI - sexually transmitted infections

IRI - immunoregulatory index

IS - immune status

FIs - HIV fusion inhibitors (according to the ATC classification: other antivirals)

ELISA - enzyme-linked immunosorbent assay

RDT - rapid diagnostic test

CLIA - chemiluminescence immunoassay

CT — computed tomography

PLHIV - people living with HIV

ICD-10 - International Statistical Classification of Diseases and Related Health Problems, 10th Revision

MO - medical organization

MRI — magnetic resonance imaging

MSM - men who have sex with men

NRTI - nucleos(t)ide reverse transcriptase inhibitors of HIV (according to the ATC classification: nucleoside and nucleotide reverse transcriptase inhibitors)

NNRTI - non-nucleoside reverse transcriptase inhibitors of HIV (according to the ATC classification: non-nucleoside reverse transcriptase inhibitors)

AE – adverse events

CBC - complete blood count

UA - urinalysis

PAS - psychoactive substances

PC - plasma concentration

Palliative care - palliative medical care

PMTCT - prevention of mother-to-child transmission

PCR — polymerase chain reaction

RC - Russian Classification of HIV Infection

RNA - ribonucleic acid

AIDS - acquired immunodeficiency syndrome

Ultrasound — ultrasound examination

PK - pharmacokinetics

FDC - fixed-dose combination

CHB - chronic viral hepatitis B

CHC - chronic viral hepatitis C

Chemoprophylaxis - chemoprophylaxis

IVF - in vitro fertilization

3TC** - Lamivudine**

ABC** - Abacavir**

ABC/3TC** - Abacavir + Lamivudine** (FDC)

ABC/ZDV/3TC** - Abacavir + Zidovudine + Lamivudine** (FDC)

ATV** - Atazanavir**

BIC/FTC/TAF** - Bictegravir + Tenofovir alafenamide + Emtricitabine**

CD - Cluster of Differentiation

CD4 - CD4+ lymphocytes (T-lymphocytes with CD4+ receptor)

CD8 - CD8+ lymphocytes (T-lymphocytes with CD8+ receptor)

COBI** (c) - Cobicistat + Tenofovir alafenamide + Elvitegravir + Emtricitabine** (FDC)

COBI/TAF/EVG/FTC** - Cobicistat + Tenofovir alafenamide + Elvitegravir + Emtricitabine** (FDC)

DOR** - Doravirine**

DOR/3TC/TDF** - Doravirine + Lamivudine + Tenofovir** (FDC)

DRV** - Darunavir**

DTG** - Dolutegravir**

DTG/3TC - Dolutegravir + Lamivudine

EFV** - Efavirenz**

ESV** - Elsulfavirin**

ETR** - Etravirine**

EVG/COBI/FTC/TDF** - Elvitegravir + Cobicistat + Emtricitabine + Tenofovir**

PhAZT** - Phosphazid**

FDA - US Food and Drug Administration

FPV** - Fosamprenavir**

FTC** - Emtricitabine**

HAV - viral hepatitis A

HBV - viral hepatitis B

HLA - human leukocyte antigen

HLA-B*5701 - allele 5701 of the B locus of the human major histocompatibility complex

IGRA - interferon-gamma release assay

LPV/r** - Lopinavir + Ritonavir** (FDC)

MVC** - Maraviroc**

NVP** - Nevirapine**

RAL** - Raltegravir**

RPV - Rilpivirine

RPV/TDF/FTC** - Rilpivirine + Tenofovir + Emtricitabine** (FDC)

RTV, r** - Ritonavir**

SQV** - Saquinavir**

TAF** - Tenofovir alafenamide**

TDF** - Tenofovir**

TDF/FTC/EFV - Tenofovir + Emtricitabine + Efavirenz

ZDV** - Zidovudine**

2DR - two-drug regimen

Terms and Definitions

Antiretroviral therapy (ART) - causal treatment of human immunodeficiency virus (HIV) infection that achieves a controlled course of the disease, prescribed for life and based on the simultaneous use of several antiretroviral drugs (according to the ATC classification: systemically acting antivirals) acting on different stages of the HIV life cycle.

Infertility - a disease characterized by the inability to achieve a clinical pregnancy after 12 months of regular unprotected sexual intercourse due to an impairment of the reproductive capacity of an individual, either alone or jointly with his/her partner.

Assisted reproductive technologies - methods of infertility treatment in which some or all stages of conception and early embryo development are carried out outside the mother's body (including the use of donor and/or cryopreserved gametes, reproductive tissues and embryos, as well as surrogacy).

Human immunodeficiency virus (HIV) - the causative agent of HIV infection belonging to the retrovirus family, causing the gradual development of immunodeficiency.

Viral load (VL) - the amount of virus in a patient's specimen (plasma, cerebrospinal fluid, etc.) determined by polymerase chain reaction (PCR) and expressed as the number of HIV ribonucleic acid (RNA) copies per 1 ml of plasma.

Viral suppression - the goal of ART, which consists in reducing and maintaining the viral load below the level detectable by available tests.

«Viral blip» (blip) - a single upward spike in viral load to a level below 200 copies/mL following an undetectable result.

Genotyping - a method based on the indirect assessment of drug resistance by comparing the consensus HIV RNA sequence with the HIV RNA sequence obtained from the patient.

Pediatric age - from birth to 17 years, 11 months, and 29 days.

Immune status (IS) - an assessment of the immune system's state. In HIV infection, the percentage and absolute counts of regulatory immune cells (helper T-lymphocytes and suppressor T-lymphocytes) and effector cells (cytotoxic T-lymphocytes), which are most critical in the disease pathogenesis, are evaluated. It is used to monitor the natural course of HIV infection and assess ART efficacy.

Immunoblotting (IB) - a laboratory immunological method for detecting antibodies in the blood against various HIV proteins. Due to its high specificity, it is used as a confirmatory method following a positive screening result.

Immunoregulatory index (IRI) - the ratio of the absolute counts of CD4 and CD8 cells. In healthy individuals, the IRI value is 1 or higher. In HIV infection, an inversion of this parameter occurs due to a decrease in the CD4 fraction; progression of immune system damage is accompanied by a decrease in IRI. It is used for prognostic purposes.

Enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CLIA) - laboratory immunological methods for the qualitative determination of total HIV antibodies in the blood. Due to their high sensitivity, they are used as screening methods.

Immunochromatographic assay (ICA) - a laboratory immunological analysis method based on the principle of thin-layer chromatography, involving a reaction between an antigen and its corresponding antibody in biological specimens. It is performed using special test strips, panels, or test cassettes.

Body mass index (BMI) - a value used to evaluate the degree of correspondence between a person's weight and height, and thereby indirectly assess whether the weight is underweight, normal, or overweight. It is important when determining appropriate pharmacological drug doses. Body mass index is calculated using the formula: BMI (kg/m²) = m / h², where m is body weight in kg, h is height in m.

Intracytoplasmic sperm injection (ICSI) - a procedure during which a single sperm is injected into the cytoplasm of an oocyte.

Artificial insemination (intrauterine insemination) - a procedure during which laboratory-processed sperm is introduced into the uterine cavity to achieve pregnancy.

Cryopreservation - the process of slow freezing or vitrification to preserve biological material (e.g., gametes, zygotes, cleavage-stage embryos, blastocysts, or gonadal tissue) at extremely low temperatures.

People living with HIV (PLHIV) - a collective term defining an individual or individuals belonging to the group of HIV-infected persons.

Infancy - from 0 to 12 months of life.

Undetectable viral load (VL) - an HIV viral load level below the detection limit of the test system or less than 50 copies/mL (it is recommended to use test systems with a sensitivity threshold of 50 copies/mL).

«Low-level viremia» - repeated viral load values in the range of 50-1000 copies/mL (low level viremia). «Low-level viremia» is a predictor of the development of HIV drug resistance.

Ovarian stimulation (ovarian hyperstimulation) - pharmacological therapy aimed at inducing follicular development in the ovaries. It can be used for two purposes: 1) for scheduled intercourse or insemination; 2) in assisted reproductive technologies, to obtain multiple oocytes during follicular puncture.

Detectable HIV viral load - an HIV viral load level above the detection threshold of the test system (it is recommended to use test systems with a sensitivity threshold of 50 copies/mL).

Palliative medical care (PMC) - medical care aimed at improving the quality of life of patients suffering from incurable progressive diseases and conditions that generally lead to premature death, as well as diseases in stages where radical treatment options are exhausted.

Embryo transfer - introduction of an embryo into the uterine cavity at any stage of development from day 1 to day 7 after in vitro fertilization or ICSI.

Perinatal HIV exposure - contact of an infant with an HIV-infected mother during gestation, labor, and breastfeeding.

Prevention of perinatal HIV transmission - a set of measures to prevent HIV infection in an infant during pregnancy, labor, and the postpartum period. It includes pharmacological methods (chemoprophylaxis) and non-pharmacological methods (operative delivery).

Polymerase chain reaction (PCR) - a laboratory method for the qualitative and quantitative determination of HIV genetic material, based on the uniqueness of nucleotide sequences in RNA/DNA regions. It has high sensitivity and specificity. Qualitative determination of HIV deoxyribonucleic acid (DNA) in blood lymphocytes is used in adults for the early detection of HIV infection during the established/suspected «serological window» period (in the first weeks after infection, when the amount of specific HIV antibodies produced in the infected person's body is insufficient for detection). Quantitative determination of HIV RNA is used when selecting drugs for ART regimens, to assess ART efficacy, and for prognostic purposes (see «Viral load»).

Embryo/fetal reduction - an intervention aimed at reducing the number of gestational sacs or embryos/fetuses in a multiple pregnancy.

Selective single embryo transfer - transfer of one (single) embryo selected from a cohort of available embryos.

Serodiscordant couples - couples maintaining a long-term sexual relationship in which only one partner has HIV infection.

Surrogate mother - a woman who carries a fetus after the transfer of an embryo to which she is not genetically related (donor embryo).

CD4 - CD4⁺ T-lymphocytes - antigen-recognizing T-helper lymphocytes, an essential component for inducing a humoral response to T-dependent antigens.

CD8 - CD8+ T-lymphocytes - T-cytotoxic lymphocytes (killer T cells) that lyse target cells bearing foreign antigens or altered self-antigens.

In vitro fertilization - a sequence of manipulations involving the extracorporeal fertilization of oocytes. It includes traditional in vitro insemination and intracytoplasmic sperm injection.

Elite controller - an individual belonging to a small group of HIV-infected patients who manage to suppress viral replication without antiretroviral therapy, due to which, despite confirmed serological infection, viral RNA is not detected in blood plasma by PCR. The prevalence of elite controllers with the ability to maintain long-term suppression of viral replication is less than 1%, while temporary control is observed somewhat more frequently.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Human immunodeficiency virus disease, or HIV infection (Eng. Human Immunodeficiency Virus Infection, HIV-infection) - a slowly progressive anthroponotic contact-transmitted disease characterized by damage to the immune system with the development of acquired immunodeficiency syndrome (AIDS). Clinical manifestations of immune system failure include opportunistic infections, malignant neoplasms, dystrophic and autoimmune processes, which, in the absence of specific treatment, lead to the death of the infected person.

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

Human immunodeficiency virus (HIV), first isolated in 1983, belongs to the retrovirus family (Retroviridae). The retrovirus family includes two subfamilies: oncoviruses (Oncoviridae) and slow lentiviruses (Lentivirus). The first subfamily includes viruses that cause leukemias: T-cell leukemia and chronic hairy cell leukemia, as well as bovine leukemia virus. HIV belongs to the lentivirus subfamily.

Currently, two virus serotypes have been described: HIV-1 and HIV-2, which differ in their structural and antigenic characteristics. HIV-1 is of the greatest epidemiological significance, dominating the modern pandemic and having the widest spread in the Russian Federation. HIV-2 is found predominantly in West African countries. Upon entering the human body, HIV affects various organs and tissues, but primarily cells bearing the CD4 marker. The CD4 receptor is present mainly on helper lymphocytes, which play a central role in the immune response, as well as on cells of the nervous system (neuroglia), monocytes, macrophages, vascular endothelium, Langerhans cells, etc.

Damage to helper T-lymphocytes (CD4) leads to a disruption of intercellular interactions within the immune system, its functional failure, gradual depletion, and, as a result, progressive immunodeficiency.

The consequence of immune system disorders is a decrease in the body's resistance. A wide range of diseases develops: secondary (opportunistic) infections, oncological, hematological, autoimmune, and lymphoproliferative diseases.

A characteristic manifestation of HIV infection is chronic inflammation affecting all organs and systems: autoimmune reactions, immune complex diseases, and metabolic disorders lead to damage to the vascular endothelium and connective tissue, with the development of cardiovascular, neurological, endocrine, and osteoarticular pathology. All of this causes multi-organ involvement and a variety of clinical symptoms.

1.3 Epidemiology of the Disease or Condition

The source of infection is a person infected with HIV at any stage of the disease. The role of an infected person as a source of infection increases in the early and late stages of the disease (the stage of primary manifestations and the stage of secondary diseases with pronounced impairment of immunoreactivity) [1-6].

Routes of transmission of the virus: natural (sexual, mother-to-child) and artificial (parenteral - injection, transfusion, transplantation, including when infected material gets onto damaged skin and mucous membranes of the eyes, nose, and oral cavity).

The virus is transmitted through blood, semen, vaginal secretions, and breast milk.

Sexual route - in recent years, it has been the dominant one in the spread of HIV infection. The probability of infection correlates with the number of sexual partners a person has and increases in inflammatory and dysplastic diseases of the genitals and rectum.

Mother-to-child transmission of HIV - can occur at any stage of pregnancy, during childbirth, and during breastfeeding. Mainly, transmission of the infection occurs in the last weeks of pregnancy and during childbirth. Without prevention, the rate of mother-to-child HIV transmission is about 40%.

Parenteral route is realized when HIV-infected material enters the internal environments of the body during medical, paramedical, and ritual procedures. Among parenteral interventions, intravenous blood transfusion carries the highest risk of infection. There is a high risk of infection with: intravenous administration of psychoactive substances using non-sterile syringes and needles; transfusion of HIV-infected blood and its products; use of medical and non-medical instruments contaminated with human biological fluids from an individual infected with HIV. In addition, donor organs and tissues used for transplantation can be sources of infection.

According to WHO data, 38.0 million people were registered worldwide with HIV infection in 2019. In 2018, the figure was 37.8 million people, respectively. The most affected region is the African Region, where more than two-thirds (25.7 million people) of the total number of people living with HIV resided in 2019. Key populations at increased risk of acquiring HIV, regardless of epidemic type or local settings, include: MSM; people who inject psychoactive substances; those in prisons and other closed settings; and sex workers.

According to the Ministry of Health of the Russian Federation, in 2020, the coverage of the Russian population with HIV testing was 24.7%, in 2019 - 28.5%, and in 2018 - 26.8%. In 2020, the incidence of HIV was 41.1 per 100,000 of the country's population, in 2019 - 54.6 per 100,000, and in 2018 - 58.6 per 100,000.

In 2019, the highest disease prevalence rates were recorded in the Kemerovo, Sverdlovsk, Irkutsk, Orenburg, Samara, Tyumen, and Tomsk Oblasts, as well as Perm and Krasnoyarsk Krais, and Altai Krai [7]. In recent years, there has been a trend towards the active involvement of women in the HIV epidemic, and the role of the sexual route of transmission among women of childbearing age has increased, which exacerbates the problem of mother-to-child transmission of HIV during pregnancy and childbirth [8].

In 2019, there was positive dynamics in the coverage of the three-stage prevention of mother-to-child transmission of HIV, rising from 88.7% in 2017 and 90.8% in 2018 to 92.4%. In 2020, 681 new cases of HIV infection were registered among the pediatric population, compared to 852 in 2019 and 977 new cases in 2018 (aged 0 to 17 years) [7].

In more than 90% of cases, infection of children with HIV occurs via perinatal contact with an HIV-infected mother and the continuation of breastfeeding [9-11]. The probability of transmitting HIV from mother to child without preventive measures is up to 40% [11,12].

The risk of intrauterine and intrapartum infection in children is estimated at 15-30%, during breastfeeding - at 5-15%, and increases if the woman is infected during pregnancy or in the late stages of the disease. Perinatal mother-to-child transmission of HIV in women with a CD4+ lymphocyte count below 350 µl^-1 occurs in 80% of cases [13,14].

Timely initiation and effectiveness of prevention of mother-to-child transmission of HIV during an uncomplicated pregnancy reduce the risk of infecting the child to 1% [10,12].

The frequency of preterm birth in the group of HIV-infected pregnant women is 17.1%, and in the group where perinatal infection occurred, it is 43.9% [15]. A pathological course of pregnancy, especially the threat of its termination, increases the likelihood of infecting the child to 2-3%, which significantly increases the importance of high-quality and effective obstetric and gynecological care for HIV-infected pregnant women [10]. Modern approaches determine the timing for initiating ART: either before pregnancy or at 13 weeks of gestation. In this case, the risk of perinatal HIV transmission is reduced to minimum values. Initiating ART at 14–27 weeks increases the risk of mother-to-child HIV transmission by 2.3 times, and at 28 weeks or later - by 4.5 times [10].

The effectiveness of preventing mother-to-child transmission of HIV is significantly influenced by continuity in the work of territorial AIDS centers and medical organizations regarding the timely detection of HIV infection in women of reproductive age, early initiation of ART in HIV-infected women during pregnancy, implementation of interventions to prevent mother-to-child transmission in HIV-infected women during labor and in newborns, and the choice of delivery method.

Measures to prevent mother-to-child transmission of HIV are carried out with the voluntary informed consent of the woman. Individual selection of the ART regimen, medical monitoring, and professional psychological support during pregnancy and childbirth determine the health status and quality of life of the future child.

1.4 Features of Coding the Disease or Condition

The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) provides codes for various conditions and medical services associated with HIV infection. Coding is intended for statistical accounting and does not imply determining the severity or prognosis of the disease. In practical use of ICD codes, they may correspond to various categories or stages in clinical classifications of HIV infection [5,6,16].

Below are the conditions and medical services associated with HIV infection, in accordance with ICD-10.

Human immunodeficiency virus [HIV] disease resulting in infectious and parasitic diseases (B20):

B20.0 - HIV disease resulting in mycobacterial infection;

B20.1 - HIV disease resulting in other bacterial infections;

B20.2 - HIV disease resulting in cytomegaloviral disease;

B20.3 - HIV disease resulting in other viral infections; B20.4 - HIV disease resulting in candidiasis;

B20.5 - HIV disease resulting in other mycoses;

B20.6 - HIV disease resulting in P. jirovecii pneumonia;

B20.7 - HIV disease resulting in multiple infections;

B20.8 - HIV disease resulting in other infectious and parasitic diseases;

B20.9 - HIV disease resulting in unspecified infectious and parasitic disease.

Human immunodeficiency virus [HIV] disease resulting in malignant neoplasms (B21):

B21.0 - HIV disease resulting in Kaposi's sarcoma;

B21.1 - HIV disease resulting in Burkitt's lymphoma;

B21.2 - HIV disease resulting in other non-Hodgkin's lymphomas;

B21.3 - HIV disease resulting in other malignant neoplasms of lymphoid, haematopoietic and related tissue;

B21.7 - HIV disease resulting in multiple malignant neoplasms;

B21.8 - HIV disease resulting in other malignant neoplasms;

B21.9 - HIV disease resulting in unspecified malignant neoplasm.

Human immunodeficiency virus [HIV] disease resulting in other specified conditions (B22):

B22.0 - HIV disease resulting in encephalopathy;

B22.1 - HIV disease resulting in lymphoid interstitial pneumonitis;

B22.2 - HIV disease resulting in wasting syndrome;

B22.7 - HIV disease resulting in multiple diseases classified elsewhere.

Human immunodeficiency virus [HIV] disease resulting in other conditions (B23):

B23.0 - Acute HIV infection syndrome;

B23.1 - HIV disease resulting in (persistent) generalized lymphadenopathy;

B23.2 - HIV disease resulting in hematological and immunological abnormalities, not elsewhere classified;

B23.8 - HIV disease resulting in other specified conditions;

B24 - Unspecified human immunodeficiency virus [HIV] disease;

F02.4 - Dementia in human immunodeficiency virus [HIV] disease (B22.0);

O98.7 - Human immunodeficiency virus [HIV] disease complicating pregnancy, childbirth and the puerperium;

R75 - Laboratory evidence of human immunodeficiency virus [HIV];

Z11.4 - Special screening examination for human immunodeficiency virus [HIV];

Z20.6 - Contact with and exposure to human immunodeficiency virus [HIV];

Z21 - Asymptomatic human immunodeficiency virus [HIV] infection status;

Z71.7 - Human immunodeficiency virus [HIV] counseling;

Z83.0 - Family history of human immunodeficiency virus [HIV] disease.

The primary ICD-10 statistical tracking codes used in the Russian Federation for medical reporting on patients with HIV infection (Form No. 61) are codes B20-B24. Since it is now scientifically proven that asymptomatic carriage of the human immunodeficiency virus does not occur, and the detection of HIV in the human body indicates the presence of the disease with varying rates of progression, the use of code Z21 for patients with a laboratory-confirmed diagnosis is incorrect. Code B23 is recommended instead.

In clinical practice, many patients with asymptomatic HIV infection present with lymphadenopathy, and their condition may correspond to category B23.1. The majority exhibit immunological abnormalities (decreased CD4 count in many patients, and CD4/CD8 ratio inversion in almost all) or hematological changes (lymphopenia, anemia, thrombocytopenia). For such patients, it is appropriate to use ICD-10 code B23.2.

1.5 Classification of the disease or condition

According to the Russian classification of HIV infection currently in force (RC, 2006) [3,5], the stage and phase of the disease are established solely based on clinical manifestations.

Viral load and CD4 count are not criteria for determining the clinical stage or phase of the disease.

Russian Clinical Classification of HIV Infection

1. Incubation stage.

2. Stage of primary manifestations.

Clinical Presentation Patterns:

A. Asymptomatic;

B. Acute HIV infection without secondary diseases;

C. Acute HIV infection with secondary diseases.

3. Subclinical stage.

4. Stage of secondary diseases.

4A. Weight loss of less than 10%, fungal, viral, and bacterial lesions of the skin and mucous membranes, recurrent pharyngitis, sinusitis, herpes zoster.

Phases:

— progression in the absence of ART, while on ART;

— remission (spontaneous, post-ART, while on ART).

4B. Weight loss of more than 10%, unexplained diarrhea or fever for more than a month, recurrent persistent viral, bacterial, fungal, and protozoal infections of internal organs, localized Kaposi's sarcoma, recurrent or disseminated herpes zoster.

Phases:

— progression in the absence of ART, while on ART;

— remission (spontaneous, post-ART, while on ART).

4C. Cachexia. Generalized viral, bacterial, mycobacterial, fungal, protozoal, and parasitic diseases, including: esophageal, bronchial, tracheal, and pulmonary candidiasis; Pneumocystis pneumonia; malignant tumors; central nervous system disorders.

Phases:

— progression in the absence of ART, while on ART;

— remission (spontaneous, post-ART, while on ART).

5. Terminal stage.

1.6 Clinical presentation of the disease or condition

The clinical presentation of HIV infection is described in the clinical guidelines "HIV Infection in Adults." Planning and management of pregnancy in women with HIV infection are described in chapters 3.1 and 7. Delivery in pregnant women with HIV infection is described in chapter 3.2 of these clinical guidelines.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Standard methods for detecting HIV antibodies (ELISA, ECLIA, Western blot) are used to diagnose HIV infection during pregnancy [17-24]. The foundation of preventing mother-to-child transmission of HIV is the timely detection of HIV infection in women of childbearing age, dispensary registration, and the initiation of ART.

Comments: pregnant women, in order to rule out HIV infection, should undergo HIV screening twice: upon registration of pregnancy and in the third trimester of pregnancy, at a gestational age of 34-36 weeks [125].

Comments: screening for HIV infection during pregnancy is performed:

— after obtaining the woman's written informed consent (Appendix A3.1);

— only upon presentation of an identity document (except in cases of emergency care) [125].

— with HIV-infected partners and pregnant women who use psychoactive substances;

— residents of the most affected regions (prevalence among pregnant women >1%) [29];

— pregnant women with signs or symptoms of acute HIV infection (e.g., fever, lymphadenopathy, skin rash, myalgia, headache, oral ulcers, leukopenia, thrombocytopenia, elevated transaminase levels).

LoE 3Grade of Recommendation B (Level of Evidence - 3).

2.1 Complaints and Anamnesis

See clinical guidelines "HIV infection in adults".

During the anamnesis collection, the obstetrician-gynecologist clarifies information regarding the pregnant woman's substance use.

2.2 Physical Examination

See clinical guidelines "HIV infection in adults".

2.3 Laboratory Diagnostics

2.3.1. Diagnosis of HIV Infection Before and During Pregnancy

If HIV infection is detected:

— the need for chemoprophylaxis to prevent HIV transmission to the child;

— possible pregnancy outcomes in HIV-infected women in the absence of PMTCT;

— the need for subsequent follow-up care (dispensary observation) of the mother and child at the local AIDS Center;

— the need to inform the sexual partner of the HIV testing results;

— criminal liability for infecting another person (sexual partner, child) with HIV.

LoE 3Grade of Recommendation A (Level of Evidence - 3).

Comments: counseling is conducted to foster adherence of pregnant women to voluntary HIV testing. Counseling is performed at the medical organization where the testing took place.

Information on pre- and post-test counseling of the pregnant woman is entered into the individual medical record of the pregnant and postpartum woman (Form 111/u) [22-24].

During pre-test counseling, the obstetrician-gynecologist (at the pregnant woman's place of care) schedules the date of her next visit to receive test results and undergo post-test counseling.

When a positive laboratory test result for HIV is detected, the obstetrician-gynecologist of the antenatal clinic or an authorized employee of the medical organization:

— no later than 12 hours from the moment of receiving a positive HIV test result, submits form 058/y "Urgent notification of an infectious disease, food poisoning, acute occupational poisoning, or unusual reaction to vaccination" to the territorial AIDS Center in the established manner;

— actively calls the pregnant woman in for counseling (test results are not communicated by telephone). A corresponding entry is made in the individual medical record of the pregnant and puerperal woman (form 111/y).

When the pregnant woman arrives, the obstetrician-gynecologist or an authorized healthcare facility employee [22-24]:

— provides post-test counseling if HIV infection is detected;

— recommends testing the sexual partners of the HIV-infected pregnant woman for HIV infection;

— indicates the HIV test result in the antenatal card, including the date and test number;

— refers the pregnant woman to the territorial AIDS Center for dispensary registration and prescription of chemoprophylaxis for mother-to-child transmission of HIV, and issues the corresponding referral using form 057/y-04;

— transmits information about the pregnant woman's referral via telephone message to the territorial AIDS Center;

— sets the date for the pregnant woman's next appointment at theantenatal clinic;

— in the event of the pregnant woman's failure to appear by the established date, arranges an active invitation for an appointment at the antenatal clinic and informs the territorial AIDS Center via telephone message about the violation of the pregnancy dispensary observation regimen.

A woman with diagnosed HIV infection must fill out the "Information on HIV Infection Detection" form (Appendix A3.2).

Referral to the territorial AIDS Center is carried out upon receipt of the first positive result for HIV-1/2 antibodies and p24 antigen (Human immunodeficiency virus HIV 1/2 + Ag p24) in the blood; repeated and confirmatory tests are not performed in the antenatal clinic setting. At the same time, the woman is informed of the need for a set of additional laboratory tests to clarify her HIV status.

Information obtained by medical personnel regarding a positive HIV test result in a pregnant woman, woman in labor, puerpera, the implementation of PMTCT, joint monitoring of the woman with specialists from the regional AIDS Prevention and Control Center, or perinatal HIV contact in a newborn is not subject to disclosure, except in cases provided for by current legislation [23,24].

Further monitoring of a pregnant woman with an established diagnosis of HIV infection is carried out jointly by an infectious disease physician from the regional AIDS Prevention and Control Center and an obstetrician-gynecologist at the local antenatal clinic. If it is impossible to refer (monitor) the pregnant woman at the regional AIDS Prevention and Control Center, monitoring is carried out by the local obstetrician-gynecologist with methodological and consultative support from an infectious disease physician of the AIDS Prevention and Control Center [23,24].

Comments: upon receiving a positive test result for the partner, it is necessary to arrange for his referral to the territorial AIDS Prevention and Control Center; simultaneously, form 058/y "Urgent notification of an infectious disease, food poisoning, acute occupational poisoning, unusual reaction to vaccination" (marked as - pregnant woman's partner) is submitted to the territorial AIDS Prevention and Control Center no later than 12 hours from the moment of detection [22-24].

2.3.2. Diagnosis of HIV infection in the maternity ward

Comments: in the most heavily affected regions (prevalence over 1%), screening of pregnant women using combined test systems with simultaneous detection of total HIV-1,2 antibodies and HIV-1 p24 antigen by a rapid method in the maternity ward can be prescribed in 100% of cases, regardless of the results of testing for class M and G antibodies (IgM, IgG) to human immunodeficiency virus HIV-1/2 and p24 antigen (Human immunodeficiency virus HIV 1/2 + Ag p24) in the blood during dispensary follow-up [38-40].

Comments: testing for HIV using rapid diagnostic test systems is carried out in the laboratory or admission department of the maternity hospital by medical personnel who have undergone special training in strict accordance with the instructions supplied with the rapid test [23,24,41,42]. It is advisable to perform rapid HIV testing before the birth of the child to ensure chemoprophylaxis of MTCT during labor.

Comments: upon receiving a positive rapid test result for HIV infection, the same blood sample must be sent to the screening laboratory of the AIDS Center for a verification test. The laboratory department of the AIDS Center shall perform the verification test as soon as possible (no later than 24 hours from the moment the sample is received).

Upon obtaining the test result, the information is immediately transmitted to the obstetric inpatient facility that referred the biological sample [22-24,41,42].

Comment: for the diagnosis of HIV infection, it is necessary to use combined test systems with the simultaneous detection of HIV-1,2 antibodies and HIV-1 p24 antigen. To minimize false-positive and false-negative test results, test systems with the best characteristics of analytical and diagnostic sensitivity and specificity for the detection of HIV-1,2 antibodies and HIV-1 p24 antigen should be used [221-224].

Comments: do not suppress lactation, perform breast milk expression [44-46].

2.3.3. Investigations for an established diagnosis

— quantitative determination of human immunodeficiency virus HIV-1 (Human immunodeficiency virus HIV-1) RNA in blood plasma by PCR [47-51];

LED 2Grade of Recommendation A (Level of Evidence 2).

— assessment of the need for opportunistic infection prophylaxis [52];

Leveled position 5Level of recommendation evidence C (level of data reliability - 5).

— screening laboratory tests for hepatitis B virus, hepatitis C virus, and tuberculosis [53-55] (see relevant clinical guidelines);

LOD 2Level of evidence B (reliability level of evidence - 2).

— screening laboratory tests for STIs caused by pathogens such as Treponema pallidum, Chlamydia trachomatis, Trichomonas vaginalis, and Neisseria gonorrhoeae [56,57] (see relevant clinical guidelines);

LOD 2Level of evidence B (reliability level of evidence - 2).

— complete blood count, general clinical blood chemistry, and urinalysis to assess renal and hepatic function [58,59];

LoE 4Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Level C (Level of Evidence - 4).

— detection of the HLA-B*5701 allele of the human major histocompatibility complex locus B if ABC** use is planned [60,61];

LOD 2Level of evidence B (reliability level of evidence - 2).

— results of previous and current molecular genetic tests of blood plasma for drug resistance mutations in human immunodeficiency virus HIV-1 (Human immunodeficiency virus HIV-1) RNA to ARVDs [62].

LoE 4Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Level C (Level of Evidence - 4).

— 4 weeks after initiating (or modifying) the ART regimen [47,67];

LOD 2Level of evidence B (reliability level of evidence - 2).

— every 4 weeks until HIV RNA levels drop below the test sensitivity threshold [47,67];

LOD 2Level of evidence B (reliability level of evidence - 2).

— thereafter, at least once every 12 weeks during pregnancy [47].

LOD 2Level of evidence B (reliability level of evidence - 2).

— during ART: at 4 and 12 weeks from treatment initiation, and thereafter once every 12 weeks [47].

LOD 2Level of evidence B (reliability level of evidence - 2).

2.4 Instrumental Diagnostics

Establishing a diagnosis of HIV infection does not imply specialized instrumental examination.

— comprehensive abdominal ultrasound for the diagnosis of gastrointestinal diseases [78].

Leveled position 5Level of recommendation evidence C (level of data reliability - 5).

2.5 Other Procedures

Diagnosis of HIV infection does not require other diagnostic methods.

— assessment of depressive symptoms and elevated anxiety, and the need for supportive therapy (e.g., consultation with a psychiatrist, or a psychiatrist-narcologist) [83-89].

LED 2Grade of Recommendation A (Level of Evidence 2).

Comments: the patient is also consulted by other specialists if appropriate symptoms are present or a diagnosis is established.

— consultation with a psychiatrist (psychotherapist, narcologist), medical psychologist, or social worker if the woman uses psychoactive substances;

— consultation with a medical psychologist.

In accordance with the Order No. 69n/95n dated February 17, 2020, "On approval of the Procedure for the provision of legal, psychological, and medical-social assistance services to women during pregnancy by medical organizations", patients (including those with diagnosed HIV infection) are entitled to a single consultation with a medical psychologist or a psychologist with a higher professional degree in "medical psychology", "clinical psychology", or "psychology" (hereinafter referred to as the specialist providing psychological assistance).

At the primary health care stage, the obstetrician-gynecologist interacts with the specialists of the women's health clinic medical-social assistance office (social work specialist, psychologist) regarding measures for the prevention of abortions, counseling on social protection issues for women applying for termination of unwanted pregnancy, fostering the woman's awareness of the necessity to carry the pregnancy to term, and providing further support during and after pregnancy.

The main activities of the specialist providing psychological assistance include psychological counseling, psychological diagnostics, psychological correction, and prevention.

The specialist providing psychological assistance performs:

• assessment of the woman's psychoemotional state;

• formation of an atmosphere of trust and cooperation;

• referral of the woman to a psychiatrist (psychotherapist);

• prevention of newborn abandonment;

• detection of postpartum depression.

The patient management tactics, the necessity and frequency of follow-up consultations are determined on an individual basis exclusively by the specialist providing psychological assistance.

If the specialist providing psychological assistance identifies signs of psychopathology in a pregnant patient with HIV infection, a consultation with a psychotherapist (psychiatrist) must be scheduled for a highly specialized assessment of the patient's condition.

Upon a positive conclusion regarding the patient's mental status, the psychotherapist (psychiatrist) determines further management tactics on an individual basis, including in-depth mental status diagnostics, deciding on the need for pharmacotherapy, observation intervals, and the number of additional consultations.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

3.1. ART during pregnancy (the first stage of prevention).

Specifics of dispensary monitoring in HIV-infected pregnant women

The recommended medical monitoring protocol for HIV-infected pregnant women is presented in Appendix B8.

Measures to prevent HIV-infected women from refusing PMTCT are presented in Appendix B12.

HIV-infected women are provided with standard antenatal medical care [22-24,92-94].

The infectious disease specialist of the regional AIDS Center prescribes ARV drugs for PMTCT, conducts a medical examination of the patient, including the determination of plasma HIV viral load and CD4+ T-cell count within the established timeframes [106,108-111] (A2).

Modification of the ART regimen in the first trimester of pregnancy is carried out by the infectious disease specialist of the regional AIDS Center [10].

Comment: if the prenatal panel decides to prolong the pregnancy or if the pregnant woman refuses to terminate the pregnancy, pregnancy monitoring is carried out by the obstetrician-gynecologist at the women's health clinic, and by the psychiatrist-narcologist at the narcology dispensary at her place of residence [22,24,92-94].

Comment: when prescribing ARV drugs for PMTCT, the HIV-infected pregnant woman fills out an informed consent for PMTCT [22-24,92-94,96] (Appendix A3.3).

Comment: explanations must be provided on the following issues [22,24,92-94,96]:

— high risk of HIV disease progression during pregnancy without ART;

— necessity of ART to prevent perinatal HIV transmission;

— necessity of ART to reduce the risk of sexual transmission of HIV to HIV-uninfected partners;

— necessity of strict adherence to the ARV dosing schedule for ART efficacy, reduction of the risk of resistance development, and risk of perinatal HIV transmission;

— possible adverse reactions to ARV drugs for women, fetuses, and newborns, including drug interactions;

— limited data on long-term outcomes of using certain ARV drugs during pregnancy in young children.

The woman must be informed about the high risk of infecting the child during pregnancy in case of refusal to undergo PMTCT, as well as the procedure for her potential criminal liability if the child is born HIV-infected [22,97].

When choosing an ART regimen for a pregnant woman, it is necessary to consider [98]:

— potential teratogenic effects and other short-term and long-term adverse effects on the fetus or newborn, including preterm birth, mutagenicity, and carcinogenicity;

— available safety data and outcomes of drug use during pregnancy;

— changes in plasma concentration of ARV drugs during pregnancy, as well as potential adverse effects for the woman, especially those that may worsen during pregnancy;

— potential drug interactions with concomitant therapy drugs;

— results of genotypic resistance testing and ART history;

— comorbid conditions;

— the patient's ability to adhere to the ART regimen, as well as the convenience of ARV drug use.

Comments: For preferred drugs, see Appendices A3.5 - A3.7.

ARVD categories and ART regimens for use during pregnancy include:

— Preferred: drugs or drug combinations for ART in pregnancy when clinical trial data in adults have demonstrated efficacy and durability with minimal adverse reactions and ease of use, and pharmacokinetic data in pregnant women are available to determine dosing. In addition, available data should indicate a favorable risk-benefit balance for the drug or drug combination compared with other ARVD options; risk-benefit assessments should include outcomes for the woman, fetus, and neonate.

— Alternative: drugs or drug combinations for ART in pregnancy when adult use data show efficacy, but data in pregnant women are limited. Some alternative ARVDs or ART regimens may have known risks of toxicity or teratogenicity that are outweighed by other benefits of use in pregnant women with HIV or HIV-infected women planning pregnancy.

— exclude the use of DTG** before 8 weeks of gestation due to the risk of neural tube defects in the fetus [104-108];

Level of Evidence 3 Strength of Recommendation C (Level of Evidence - 3).

— if pregnancy occurs in HIV-infected women receiving DTG**, counseling is necessary regarding the risks and benefits of continuing DTG** versus switching to another ART regimen [106];

Leveled position 5Level of recommendation evidence C (level of data reliability - 5).

— prescribe NVP** only when the CD4 count is <250 cells/μL^-1 [108];

LOD 2Level of evidence B (reliability level of evidence - 2).

— prescribing ATV** without a booster – RTV**;

— prescribing FPV**, RTV** (as the sole PI), SQV** to pregnant women;

— prescribing two-drug ART regimens or three-NRTI ART regimens (e.g., ABC/ZDV/3TC**);

— prescribing DTG/3TC** and DTG/RPV, as there are no data on their use during pregnancy. The ART regimen must be adjusted if pregnancy occurs [69].

Leveled position 5Level of recommendation evidence C (level of data reliability - 5).

— prescribing regimens containing EVG/c, due to pharmacokinetic changes and low efficacy in the 2nd and 3rd trimesters of pregnancy. If pregnancy occurs, a switch to a more effective regimen recommended for pregnant women should be considered [110]. If any of these regimens are continued, viral load must be monitored every 4-8 weeks;

Leveled position 5Level of recommendation evidence C (level of data reliability - 5).

— prescribing TAF**-containing regimens to treatment-naive pregnant women. Treatment with a TAF**-containing regimen may be continued during pregnancy in women who have previously received TAF**, provided it is effective and free of adverse reactions [226,227].

LoE 3Grade of Recommendation B (Level of Evidence - 3).

3.2. Prevention of MTCT during labor (second stage of prevention)

Before preventive measures are initiated, the parturient woman signs a standard informed consent form [22-24,125] (Appendix A3).

At 36-37 weeks of gestation, a complete clinical diagnosis is formulated, and the place of planned delivery is determined (Order of the Russian Ministry of Health No. 1130n dated October 20, 2020).

To ensure PMTCT, the obstetric hospital must maintain a constant adequate supply of ARVDs.

PMTCT procedures during labor are performed by the obstetrician-gynecologist attending the delivery, in accordance with PMTCT guidelines [124,125].

The ART regimen prescribed to the woman must be taken into account when treating postpartum uterine hemorrhage to avoid drug-drug interactions.

Comments:

— in parturient women with a positive rapid HIV test result;

— when it is impossible to perform a rapid test or obtain timely results of a standard HIV antibody test in a parturient woman;

— in parturient women with a negative rapid HIV test result who are substance abusers and/or have a substance-abusing partner (within 12 weeks prior to delivery);

— in parturient women with a negative rapid HIV test result who had sexual contact with a known HIV-infected individual (within 12 weeks prior to delivery) [125];

Comments: Contraindications include HIV resistance to ZDV** or a history of adverse reactions to ZDV**. In this case, the selected treatment regimen without ZDV** is continued during labor.

The solution preparation procedure and infusion rate calculation are determined in accordance with the reference table (Appendix A3.9).

Comments: artificial rupture of membranes may be performed according to standard obstetric indications in HIV-infected women with an undetectable HIV viral load who are receiving ART [137].

Comments: if chemoprophylaxis during labor is not feasible, cesarean section can serve as an independent preventive procedure to reduce the risk of mother-to-child HIV transmission during labor, although it is not recommended if the water-free interval exceeds 4 hours.

The final decision on the mode of delivery for an HIV-infected woman is made by the attending obstetriciangynaecologist on an individual basis, taking into account the condition of the mother and fetus, weighing the benefit of reducing the risk of child infection via cesarean section against the likelihood of postoperative complications and the clinical course of HIV infection [22,24,128].

Comments: during a cesarean section, intravenous administration of ZDV solution is prescribed 4 hours before the surgical intervention at the same doses as for spontaneous delivery and is discontinued at the moment of separation of the infant from the mother (clamping of the umbilical cord) [126].

4. Medical Rehabilitation and Sanatorium-Resort Treatment

See clinical guidelines "HIV infection in adults".

5. Prevention and Dispensary Observation

5.1. Prevention

HIV prevention is described in the clinical guidelines «HIV Infection in Adults». The stages of preventing HIV transmission in pregnant women are described in Chapter 3 of these clinical guidelines.

5.2. Specifics of dispensary monitoring

An HIV-infected pregnant woman is followed up at the antenatal clinic at her place of registration on a general basis in accordance with Article 14 of Federal Law No. 38-FZ of May 30, 1995, «On Preventing the Spread in the Russian Federation of the Disease Caused by the Human Immunodeficiency Virus (HIV Infection)» [24,94].

An HIV-infected pregnant woman is monitored by an infectious disease specialist and an obstetrician-gynaecologist at the territorial AIDS Prevention and Control Center simultaneously with follow-up at the antenatal clinic at her place of registration [22-24].

If it is not possible to refer (monitor) a pregnant woman to the AIDS Prevention and Control Center of a constituent entity of the Russian Federation, follow-up is carried out by the obstetrician-gynaecologist at the place of residence with methodological and consultative support from the infectious disease specialist of the AIDS Prevention and Control Center [22,24,92].

During the period of monitoring an HIV-infected pregnant woman, the obstetrician-gynaecologist of the antenatal clinic sends information to the AIDS Prevention and Control Center of the constituent entity of the Russian Federation regarding the course of pregnancy, comorbid conditions, pregnancy complications, and laboratory test results in order to adjust ARV PMTCT and/or ART regimens, and requests information from the AIDS Prevention and Control Center of the constituent entity of the Russian Federation on the specific clinical features of HIV infection in the pregnant woman and the ARV administration regimen, coordinating the necessary diagnostic and treatment methods taking into account the woman's health status and the course of pregnancy [22].

Throughout the entire monitoring period of an HIV-infected pregnant woman, the obstetrician-gynaecologist of the antenatal clinic, under conditions of strict confidentiality (using a code), notes in the woman's medical documentation her HIV status, the presence (absence) and intake (refusal of intake) of ARVs required for PMTCT prescribed by specialists of the AIDS Prevention and Control Center [22,24,92].

The obstetrician-gynaecologist of the antenatal clinic immediately informs the AIDS Prevention and Control Center of the constituent entity of the Russian Federation if the pregnant woman lacks ARVs or refuses to take them, in order to take appropriate measures.

The infectious disease specialist of the AIDS Center (taking into account the opinion of the obstetrician-gynaecologist), at each visit of the pregnant woman starting from 22 weeks of gestation, issues and provides the patient with a medical report indicating: diagnosis, ART regimen, information on CD4 count results, and blood plasma HIV-1 viral load [66,67].

The labor management tactics and choice of HIV chemoprophylaxis regimen for the infant are determined based on the results of quantitative HIV-1 RNA PCR blood testing in the woman at 34-36 weeks of gestation [66,67].

Based on the results of the HIV-1 RNA PCR blood test at 34-36 weeks of gestation, the infectious disease specialist of the AIDS Center issues a medical report indicating the diagnosis, ART regimen, CD4 count results, and blood HIV-1 viral load [66,67].

6. Organization of Medical Care

For the organization of medical care delivery for HIV infection, see the clinical guidelines «HIV Infection in Adults».

Labor management tactics and timing of hospitalization in an obstetric inpatient facility for pregnant women with HIV, based on the results of quantitative HIV-1 RNA PCR blood testing in the woman at 34-36 weeks of gestation, are defined in Chapter 3.2.

7. Additional Information

7.1. Pregnancy planning in HIV-infected women

— provide information on effective and appropriate contraceptive methods to reduce the likelihood of an unintended pregnancy [140];

LED 2Grade of Recommendation A (Level of Evidence 2).

Comment: HIV infection is not a contraindication for any method of contraception; however, drug interactions between hormonal contraceptives and antiretroviral drugs (according to the ATC classification: antivirals for systemic use) must be taken into account.

— refer the woman and her sexual partner for STI screening and treatment prior to planned pregnancy [141-145];

LED 2Grade of Recommendation A (Level of Evidence 2).

— explain the need to prescribe ART to maximally suppress HIV replication before a planned pregnancy in order to reduce the risk of mother-to-child HIV transmission [95,100].

LED 2Grade of Recommendation A (Level of Evidence 2).

— the HIV-infected sexual partner of the woman also needs to be prescribed ART for sustained viral suppression before a planned pregnancy [122-124,146,147].

LED 2Grade of Recommendation A (Level of Evidence 2).

— explain potential adverse events and the teratogenic effects of certain ARVs and ART regimens, as well as possible adverse maternal and fetal outcomes. Encourage the woman to use ARVs that are safe during pregnancy [148].

Comment: when selecting or evaluating an ART regimen for women of childbearing potential with HIV, the safety and efficacy of the regimen, as well as the woman's hepatitis B and C status, must be considered.

LoE 4Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Level C (Level of Evidence - 4).

— prescribing ART to the HIV-infected partner [122-124];

LED 2Grade of Recommendation A (Level of Evidence 2).

— planning pregnancy using assisted reproductive technology procedures via intracytoplasmic sperm injection (IVF-ICSI) [149].

LOD 2Level of evidence B (reliability level of evidence - 2).

7.2. Assisted reproductive technologies and artificial insemination in HIV infection

HIV infection is not a contraindication to providing medical care to patients using ART and artificial insemination.

From the perspective of indications for reproductive technologies, HIV-infected patients can be divided into 2 groups:

— patients with normal fertility status (no pathology associated with infertility). These are discordant couples (only one partner is a carrier) who use barrier protection during sexual intercourse to prevent infecting the HIV-negative partner;

— concordant (both partners are infection carriers) and discordant couples who have infertility.

The choice of a safe pregnancy-achieving program is determined by an ART specialist ex consilio with the attending infectious disease specialist, while informing the patients about the potential risks of transmitting the infection to the partner and the future child.

Comments: HIV-infected women undergoing ART and/or artificial insemination must meet the following conditions [150]:

1. Presence of stage 3 (subclinical) or stages 4A, 4B, 4C in remission lasting at least 6 months.

In stages 1, 2A, 2B, 2C, it is recommended to postpone ART until the disease transitions to the subclinical stage. In stages 4A, 4B, 4C in the progressive phase, it is recommended to postpone ART until the disease transitions to remission lasting at least 6 months.

2. Prescription of ART:

— prior to ART procedures, it is recommended to prescribe ART regardless of the presence of clinical and laboratory indications for initiating HIV treatment. Once pregnancy occurs, ART should be continued throughout the entire gestation period until delivery, during labor, and postpartum;

— when prescribing ART, preference should be given to drugs with lower mitochondrial toxicity;

— when prescribing ART, preference should be given to drugs with lower mitochondrial toxicity, as there is evidence of gonadal toxicity associated with certain NARTI drugs.

3. Undetectable viral load in blood (HIV RNA level <50 copies/mL) for more than 6 months.

4. Before using ART and artificial insemination, as well as during the procedure and pregnancy, HIV-discordant partners should use a condom during every sexual contact.

5. A conclusion by an infectious disease specialist from the AIDS Center regarding the feasibility of performing ART and/or artificial insemination at present, indicating the stage and phase of HIV infection, results of laboratory tests performed twice within the last 6 months (CD4+ lymphocyte count, viral load).

6. Absence of contraindications to ART and/or artificial insemination based on examination results.

Principles of organization of the ART department [150]:

— requirements for the conditions of providing medical care using ART and artificial insemination to HIV-infected patients are similar to those for all infections transmitted through contact with patient blood;

— work with sperm samples, oocytes, and embryos of HIV-infected individuals must be performed in a class II laminar flow cabinet;

— work with sperm samples, follicular fluid, and embryos of HIV-infected patients, as well as invasive procedures (transvaginal oocyte retrieval, embryo transfer, intrauterine insemination), should be performed during specially designated hours/days or in separate rooms;

— every sperm sample and follicular aspirate should be handled as a potential source of bloodborne infections. Separate storage of washed sperm samples from HIV-positive men from the general stream of samples must be ensured. Sperm samples and follicular aspirates from HIV-infected patients must be labeled;

— cryopreservation of oocytes and sperm samples is recommended to be carried out in closed carriers, and storage in nitrogen vapor in a dedicated Dewar vessel designated for this group of patients;

— cryopreservation of embryos is recommended to be carried out in closed cryocarriers (no more than one embryo per carrier in case of female HIV infection), and storage in nitrogen vapor in a dedicated Dewar vessel designated for this group of patients;

— upon completion of work, cleaning and disinfection of the room and equipment used must be carried out.

7.2.1. Artificial insemination in couples where the woman is HIV-infected

Comments: invasive medical interventions in multiple pregnancies (embryo reduction, surgical correction of cervical incompetence, etc.) may lead to an increased risk of mother-to-child transmission of HIV.

The IUI procedure should be performed during specially designated hours/days or in separate rooms [150].

Upon completion of work, cleaning and disinfection of the room and equipment used must be carried out [150].

7.2.2. Artificial insemination in couples where the man is HIV-infected

During counseling by an infectious disease specialist from the AIDS Center and an ART Center specialist, detailed information should be provided on the artificial insemination method and the probability of the risk of infection of the woman during artificial insemination using prepared sperm from her husband (partner).

Comments: following processing, the fertility parameters of sperm may decrease, which makes IVF the preferred program in terms of pregnancy success rates.

Before performing artificial insemination, it is necessary to verify that the woman is not infected with HIV.

7.2.3. Use of ART in couples where the woman is HIV-infected

Comment: prior to ART, the fertilization method (IVF or ICSI) should be selected depending on the infertility factor [151]. The HIV status of the partners does not determine the fertilization method. There is a view that the virus may be present in follicular fluid and attach to granulosa cells surrounding the oocyte; therefore, it is necessary to completely strip the oocyte of cumulus cells, wash it in a medium, and perform fertilization via ICSI [154].

Comments: transfer of 2 embryos must be justified by the clinical and embryological situation with the informed voluntary consent of the patients.

Principles of ART:

1. Ovarian stimulation should be performed according to standard principles.

2. Ovarian follicular puncture and embryo transfer should be performed during specially designated hours (as the last procedures of the day) or in separate rooms [150].

3. Cultivation of gametes and embryos is carried out in a separate incubator [150].

4. Embryo cryopreservation is carried out in closed cryocarriers (no more than one embryo per carrier), and storage is performed in nitrogen vapor in a dedicated Dewar vessel designated for this group of patients.

5. Endometrial preparation for the transfer of a thawed cryopreserved embryo is performed according to standard principles.

7.2.4. ART in couples where the man is HIV-infected

During counseling by an infectious disease specialist and/or an ART Center specialist, the woman and man are provided with detailed information on the method and the probability of the risk of infection of the woman during IVF, ICSI, and IUI using specially prepared sperm from the husband (partner) in order to choose a safe option for achieving pregnancy (including for the future child, via ART or IUI).

Before performing ART, it is necessary to verify that the woman is not infected with HIV [150].

However, HIV infection is not a contraindication to providing medical care to patients (women and men) using ART and IUI, except for the forms and stages specified in paragraph 3 of the List of Contraindications, specifically at the stage [150]:

• incubation (stage 1);

• primary manifestations (2A, 2B, 2C);

• secondary diseases in the progressive phase (4A, 4B, 4C);

• terminal (stage 5).

Level of Evidence (LoE) 1Grade of Recommendation (GoE) A (Level of Evidence: 1).

Comments: at stages 1, 2A, 2B, and 2C, it is recommended to postpone ART until the disease progresses to the subclinical stage. At stages 4A, 4B, and 4C in the progressive phase, ART should be postponed until the disease enters a remission phase lasting at least 6 months. At any stage: absence of ART. Failure to meet the condition: HIV viral load <50 copies/mL for more than 6 months [150].

• the fertilization method (IVF or ICSI) is recommended to be selected depending on the infertility factor [151].

Level of Evidence (LoE) 1Grade of Recommendation (GoE) B (Level of Evidence: 1).

Comments: the HIV status of the partner(s) does not determine the fertilization method. There is an opinion that ICSI is safer regarding HIV transmission compared to conventional IVF. This assumption is based on the fact that ICSI lacks prolonged contact of the oocyte with a relatively large volume of sperm suspension. However, there is no scientific evidence for this. No cases of HIV transmission to a child or mother have been registered worldwide when using ART with standard sperm processing methods in serodiscordant couples. Furthermore, the theoretical possibility of oocyte infection with HIV during ICSI has been experimentally proven, although the probability of this event is 0.00002% [156].

Principles of ART:

1. Ovarian stimulation is carried out according to generally accepted principles.

2. Cultivation of gametes and embryos is carried out in a separate incubator [150].

3. Embryo cryopreservation is performed using closed cryodevices, and storage is carried out in nitrogen vapor in a Dewar flask specifically designated for this patient group.

7.2.5. ART in HIV-concordant couples

In HIV-1 concordant couples, there is a probability of superinfection if the partners are infected with different strains of the virus. As a result, the course of the infection worsens and additional difficulties arise in selecting effective ART. Therefore, ART is recommended specifically in concordant couples depending on fertility status to achieve reproductive function.

Principles of ART:

1. Ovarian stimulation should be performed according to generally accepted principles.

2. Ovarian follicular puncture and embryo transfer should be performed during hours specially designated for this purpose (as the last procedures of the day) or in separate rooms.

3. Cultivation of gametes and embryos is carried out in a separate incubator [150].

4. Embryo cryopreservation is performed in closed cryodevices (no more than one embryo per device), and storage is carried out in nitrogen vapor in a Dewar flask specifically designated for this patient group.

Comments: transfer of 2 embryos must be justified by the clinical and embryological situation with the informed voluntary consent of the patients.

7.2.6. Surrogacy

Transfer of embryos from HIV-infected prospective parents to a surrogate mother is permitted after obtaining her informed voluntary consent, following consultation with an infectious disease specialist at the AIDS and Infectious Diseases Prevention and Control Center, and after providing her with full information about potential health risks [150].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

Adamyan Leila V. — Academician of the Russian Academy of Sciences, Professor, Honored Scientist of the Russian Federation, Deputy Director for Research at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, Chief freelance Specialist in Obstetrics and Gynecology of the Ministry of Health of the Russian Federation, Head of the Department of Reproductive Medicine and Surgery at the Faculty of Professional Development of Physicians of A.I. Evdokimov Moscow State University of Medicine and Dentistry, member of the Russian Society of Obstetricians and Gynecologists (Moscow).

Baranov Igor I. — Doctor of Medical Sciences, Professor, Head of the Organizational and Methodological Department of the Scientific and Organizational Support Service at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Russian Ministry of Health, member of the Russian Society of Obstetricians and Gynecologists (Moscow).

Belova Elena G. — Candidate of Medical Sciences, Infectious Diseases Physician at the HIV Prevention Department of the Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department, member of the NP "National Virological Association".

Bessarab Timur P. — Candidate of Medical Sciences, Head of the HIV Prevention Department of the Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department, member of the NP "National Virological Association".

Vlatskaya Yulia F. — Candidate of Medical Sciences, Head of the Outpatient Pediatric Department of the Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department, member of the NP "National Virological Association".

Volodin Nikolai N. — Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, President of the All-Russian Public Association "Russian Association of Perinatal Medicine Specialists".

Geine Margarita D. — Clinical Laboratory Diagnostics Physician at the Central Laboratory for HIV Diagnostics of the Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department, member of the NP "National Virological Association".

Denisova Elena V. — General Practitioner at the HIV Prevention Department of the Center for Prevention and Control of AIDS, Moscow Healthcare Department, member of the NP "National Virological Association".

Ivannikov Evgeny Vasilyevich — Head of the Outpatient Department, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Konoplyannikov Alexander Georgievich — Doctor of Medical Sciences, Professor, Department of Obstetrics and Gynecology, Pediatric Faculty, Russian State Medical University.

Kuzmin Vladimir Nikolaevich — Doctor of Medical Sciences, Professor, Department of Obstetrics and Gynecology, A.I. Evdokimov Moscow State University of Medicine and Dentistry of the Russian Ministry of Health (Moscow).

Kurtser Mark Arkadievich — Doctor of Medical Sciences, Academician of the Russian Academy of Sciences, Head of the Department of Obstetrics and Gynecology, Pediatric Faculty, N.I. Pirogov Russian National Research Medical University; Chairman of the Presidium of the Moscow Association of Obstetricians and Gynecologists.

Litvinova Natalia Gennadievna — Infectious Diseases Physician, Outpatient Department, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Mazus Alexey Israilevich — Doctor of Medical Sciences, Head of the Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department, and the International Virology Center of the RUDN University Medical Institute; Chief Freelance Specialist in HIV Infection, Ministry of Health of the Russian Federation and Moscow Healthcare Department; Chairman of the Board, National Partnership "National Virological Association".

Mityurina Elena Viktorovna — Candidate of Medical Sciences, Senior Research Scientist, F. Paulsen Research and Clinical Department of Assisted Reproductive Technologies, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

Nabiulina Dinara Rinatovna — Infectious Diseases Physician, Outpatient Department, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Nazarenko Tatyana Alekseevna — Professor, Doctor of Medical Sciences, Director of the Institute of Reproductive Medicine, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

Olenev Anton Sergeevich — Candidate of Medical Sciences, Chief Freelance Specialist in Obstetrics and Gynecology, Head of the Perinatal Center Branch, City Clinical Hospital No. 24 of the Moscow Healthcare Department; member of the Interdisciplinary Association of Reproductive Medicine Specialists.

Olshansky Alexander Yakovlevich — Candidate of Medical Sciences, Head of the Central Laboratory for HIV Diagnostics, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department.

Perminova Svetlana Grigorievna — Doctor of Medical Sciences, Associate Professor, Leading Research Scientist, F. Paulsen Research and Clinical Department of Assisted Reproductive Technologies, V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology.

Serebryakov Egor Mikhailovich — Head of the Organizational and Methodological Department, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Spassky Maxim Evgenievich — Psychotherapist, HIV Prevention Department, Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Tuglanova Bela Mukhamedovna — Infectious Diseases Physician, HIV Prevention Department, Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Tsyganova Elena Valerievna — Candidate of Medical Sciences, Chief Freelance Specialist for HIV Infection of the Central Federal District, Deputy Chief Freelance Specialist in Infectious Diseases of the Moscow Healthcare Department, Head of the Research and Clinical Department, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Shimonova Tatyana Evgenievna — Candidate of Medical Sciences, Epidemiologist, Moscow City Center for Prevention and Control of AIDS, Moscow Healthcare Department; member of the National Partnership "National Virological Association".

Conflict of interest. All members of the working group declared no financial support / conflict of interest that needs to be disclosed.

Appendix A2. Methodology for Developing Clinical Guidelines

Methods used to assess the quality and strength of evidence:

• reviews of published meta-analyses;

• systematic reviews with evidence tables;

• expert consensus;

• significance assessment in accordance with the rating scheme (schemes attached).

The guidelines were discussed and approved by members of the National Association of Specialists in the Prevention, Treatment, and Diagnosis of HIV Infection, and the working group of the Profiling Commission for the Diagnosis and Treatment of HIV Infection of the Russian Ministry of Health.

In these clinical guidelines, all information is ranked by the level of reliability (evidence) based on the quantity and quality of studies on the issue. The evidence base for the recommendations consisted of publications included in the Cochrane Library, EMBASE, PUBMED, and MEDLINE databases. The significance of the recommendations is assessed in accordance with the classification of their reliability and evidence levels (rating scheme).

The method used to formulate the recommendations was expert consensus.

Methods of recommendation validation:

• internal expert review;

• compliance analysis with regulatory framework;

• external expert review.

Evidence Analysis Methodology

Selection of publications as potential sources of evidence based on the validity level of each study.

The impact of the evidence level assigned to a publication on the strength of the recommendations derived from it.

To minimize potential errors due to subjective factors, each study was evaluated independently by at least two independent members of the working group. Any discrepancies in evaluations were discussed by the full working group. If consensus could not be reached, independent experts among the most experienced were engaged

specialists of territorial centers for the prevention and control of AIDS.

The target audience for these clinical guidelines includes specialists with higher medical education in the following specialties:

• infectious diseases;

• internal medicine;

• general medical practice (family medicine);

• obstetrics and gynecology;

• epidemiology;

• clinical laboratory diagnostics.

The clinical guidelines may be used in the development of training and methodological toolkits for the training and professional retraining of physicians. Scales for assessing the levels of evidence reliability (LER) for diagnostic, preventive, therapeutic, and rehabilitation methods (interventions) and the scale for assessing the levels of recommendation persuasiveness (LRP) for preventive, diagnostic, therapeutic, and rehabilitation methods (interventions).

Scale for assessing the levels of evidence reliability (LER) for diagnostic methods (diagnostic interventions)

Scale for assessing the levels of evidence reliability (LER) for preventive, therapeutic, and rehabilitation methods (preventive, therapeutic, and rehabilitation interventions)

Scale for assessing the levels of recommendation persuasiveness (LRP) for preventive, diagnostic, therapeutic, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitation interventions)

Procedure for updating clinical guidelines — once every two years.

Appendix A3. Reference Materials

HIV infection and the legislation of the Russian Federation

Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation".

Federal Law No. 181-FZ dated November 24, 1995 (as amended on July 29, 2018) "On Social Protection of Disabled Persons in the Russian Federation".

Federal Law No. 38-FZ dated March 30, 1995, "On the Prevention of the Spread in the Russian Federation of the Disease Caused by the Human Immunodeficiency Virus (HIV Infection)".

Order of the Ministry of Health of the Russian Federation No. 689n dated November 8, 2012, "On Approval of the Procedure for Providing Medical Care to the Adult Population for the Disease Caused by the Human Immunodeficiency Virus (HIV Infection)".

Order of the Ministry of Health of the Russian Federation No. 824n dated October 2, 2019, "On Approval of the Procedure for Organizing High-Tech Medical Care Using the Unified State Health Information System".

Resolution of the Chief State Sanitary Doctor of the Russian Federation No. 4 dated January 28, 2021, "On Approval of Sanitary Rules and Norms SanPiN 3.3686-21 'Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases'".

Order of the Ministry of Health of the Russian Federation No. 1130n dated October 20, 2020, "On Approval of the Procedure for Providing Medical Care in the Field of 'Obstetrics and Gynecology'".

Order of the Moscow City Health Department dated August 17, 2018 № 563 "On further improvement of measures for the prevention of perinatal HIV transmission in medical organizations of the Moscow state healthcare system".

Appendix A3.1. Informed consent for HIV screening.

I, _____________________________________________________________________________

(last name, first name, middle name)

___________________ born on _______________, I hereby confirm that, based on the information provided to me, freely and without coercion, and being aware of the consequences of the examination, I have decided to undergo HIV antibody testing. For this purpose, I consent to give a blood test.

I confirm that it has been explained to me why HIV testing is important, how the test is performed, and what consequences HIV testing may have.

I have been informed that:

- HIV testing is carried out at the AIDS Center and other medical institutions. Depending on my voluntary choice, testing can be voluntary and anonymous (without presenting documents and stating a name) or confidential (upon presentation of a passport, the result will be known to the examinee and the attending physician). HIV testing is free of charge in state medical institutions;

- proof of HIV infection is the presence of HIV antibodies in the blood of the person being tested. At the same time, during the period between infection and the appearance of HIV antibodies (the so-called "seronegative window", usually 3 months), HIV antibodies are not detected during testing, and the tested person can infect others; - HIV infection is transmitted through only three routes:

- parenteral – most frequently through drug use, but can also be transmitted through the use of non-sterile medical instruments, blood component transfusions, tattooing, piercing with contaminated instruments,

sharing other people's razors and manicure accessories;

- through unprotected sexual contact;

- from an HIV-infected mother to her child during pregnancy, childbirth, and breastfeeding.

Appendix A3.2. Counseling on the detection of HIV infection

Counseling on the detection of HIV infection

I, _________________________________________________________________________

(last name, first name, middle name)

___________________ born on _______________, hereby confirm that I have been informed of the detection of HIV infection in me; the meaning of this diagnosis has been explained to me.

I have been informed that:

- the presence of HIV antibodies, epidemiological and clinical data is proof of the presence of HIV infection;

- for dispensary follow-up, clarification of the disease stage, and prescription of treatment, I need to contact the Center for Prevention and Control of AIDS. It has been explained to me that:

- HIV-infected individuals are provided with all types of medical care on a general basis according to clinical indications in accordance with the legislation of the Russian Federation on the protection of citizens' health;

- HIV-infected citizens of the Russian Federation possess all rights and freedoms on its territory and perform duties in accordance with the Constitution of the Russian Federation and the legislation of the Russian Federation;

- currently in Russia, there is free examination and treatment (antiretroviral therapy) for in-need HIV-infected individuals. For monitoring and treatment, I am advised to immediately contact the territorial AIDS Center. Antiretroviral therapy does not cure HIV infection, but it stops the replication of the virus, significantly prolongs the patient's life, and reduces the likelihood of transmitting the disease. It is important for HIV-infected pregnant women to contact the AIDS Center as early as possible and start taking special medications to prevent infection of the unborn child;

- HIV infection is transmitted through only three routes:

1. Through unprotected sexual contact.

2. Through blood – most frequently through drug use, but can also be transmitted through the use of non-sterile medical instruments, blood component transfusions, tattooing, piercing with contaminated instruments, sharing other people's razors, manicure accessories, and toothbrushes.

3. From an HIV-infected mother to her child during pregnancy, childbirth, and breastfeeding.

- HIV infection is not transmitted in everyday life through handshakes, sharing tableware, swimming pools, toilets, shared meals, or insect bites;

- I must observe precautions so as not to infect other people with HIV. Others can be protected from HIV infection if I avoid dangerous contacts with them (people must not come into contact with blood, genital secretions, and breast milk of an HIV-infected person). I have been advised to inform my sexual partners of my HIV status and to always use condoms correctly. Others should be protected from contact with an HIV-infected person's blood; I must use only personal hygiene items (razors, manicure accessories, toothbrushes), sterile medical instruments when necessary, and avoid drug use;

- HIV-infected individuals cannot be donors of blood, biological fluids, organs, or tissues.

- There is criminal liability for knowingly exposing another person to the risk of HIV infection or infecting another person with HIV infection (Article 122 of the Criminal Code of the Russian Federation, Collection of Legislation of the Russian Federation);

- questions can be directed to the territorial AIDS Center.

______________________________ signature of the person tested for HIV _______________ date

Appendix A3.3. Informed consent for chemoprophylaxis of mother-to-child transmission of HIV during pregnancy and childbirth

Informed consent for chemoprophylaxis of mother-to-child transmission of HIV during pregnancy and childbirth

I _____________________________________________________________ (last name, first name, patronymic in full),

__________________ born on _______________, hereby confirm my voluntary consent to take medications aimed at preventing the infection of my unborn child with the human immunodeficiency virus and/or treating HIV infection.

I confirm that it has been explained to me in an accessible form why taking these medications is necessary, and the mechanism of action of the drugs prescribed to me and my unborn child has been explained.

I have been informed that:

- the drugs prescribed to me reduce the viral load in my body and prevent HIV infection;

- adherence to the drug regimen reduces the probability of infecting the unborn child;

- nevertheless, even with absolute compliance with all medication rules, there is no absolute guarantee of preventing infection of the unborn child; the risk of child infection is up to 1%;

- if I refuse to take the prescribed medications or violate the adherence regimen, the risk of infection increases up to 40%;

- all medicinal products prescribed to me and my unborn child are approved for use in Russia;

- like any medicinal product, the drugs prescribed to me and my unborn child may cause certain adverse reactions, about the potential occurrence of which I have been informed;

- if, as a result of taking the prescribed medications, a threat arises to my health or the health of the unborn child, chemoprophylaxis/treatment may be discontinued by decision of the attending physician;

- that putting my child to the breast and/or feeding them with my breast milk places the child at risk of HIV infection;

- that formula feeding is a safe method of feeding my child.

I undertake to:

- undergo medical examinations to monitor the efficacy of the prescribed medications according to the established schedule, fill out the questionnaires provided for this purpose, and take lab tests;

- take the prescribed medicinal products strictly in accordance with the attending physician's prescription;

- inform the attending physician about all violations in taking the prescribed medications or the discontinuation thereof for any reason;

- inform the attending physician about all changes in my health status and do so promptly (within 24 hours) if I believe these changes are related to taking the prescribed medications;

- not take any other medicinal products (even if prescribed by another doctor) without consulting the attending physician who prescribed my chemoprophylaxis/treatment. If taking these medications is unavoidable (e.g., in urgent or emergency cases), I must inform the attending physician about it.

Patient's signature ______________________________ Date: _____________________

Attending physician's signature __________________________ Date: _____________________

Appendix A3.4. FDA-established pregnancy risk categories for medicinal products

FDA-established pregnancy risk categories for medicinal products

Appendix A3.5. Use of ARV drugs in pregnant women with HIV infection: human pregnancy PK and toxicity data and recommendations for use during pregnancy

Appendix A3.6. ARV regimens for pregnant women naive to ART

ARV regimens for pregnant women naive to ART [12,96,98,106,109-121]

Appendix A3.7. Recommendations for the use of ARV drugs in HIV-infected pregnant women and HIV-infected women planning pregnancy [12,96,98,106,109-121]

CCR5 receptor antagonist (ATC classification: other antivirals)

Appendix A3.8. Schedule of routine examinations and assessments for HIV-infected pregnant women during follow-up at the territorial AIDS center

Additional laboratory tests

Appendix A3.9. Guidelines for the prevention of mother-to-child transmission of HIV in maternity hospitals (departments)

Guidelines for the prevention of mother-to-child transmission of HIV in maternity hospitals (departments)

Upon admission of a pregnant woman to the maternity ward, she continues the ART prescribed during pregnancy. If the woman has not received ART, she is prescribed:

- Zidovudine/Lamivudine** (INN: Zidovudine + Lamivudine**) 0.3 g/0.15 g

1 tablet 2 times a day;

- Lopinavir/Ritonavir** (INN: Lopinavir + Ritonavir**) 0.2 g/0.05 g

3 tablets 2 times a day, every 12 hours;

- on the day of delivery - Lamivudine** 0.15 g 1 tablet every 12 hours, Lopinavir/Ritonavir** (INN: Lopinavir + Ritonavir**) 0.2 g/0.05 g 3 tablets

every 12 hours.

At the onset of labor: Zidovudine** intravenous infusion 2 mg/kg over 1 hour (loading dose), 1 mg/kg/h (maintenance dose) throughout labor until the umbilical cord is clamped. Preparation procedure for Zidovudine** solution: add 2 vials (40 ml) of Zidovudine** injection solution 10 mg/ml to 500 ml of 5% dextrose** solution. The resulting concentration is 0.0008 g/ml (0.8 mg/ml).

Ratio of volumes of ZDV** for IV administration and 5% dextrose** solution

Zidovudine** dosing schedule for intravenous infusion

1. In case of cesarean section, infusions are started 4 hours before surgery and continued until the umbilical cord is clamped.

Appendix A3.10. Informed consent for antiretroviral therapy in a child to prevent mother-to-child transmission of HIV infection

Informed consent for antiretroviral therapy in a child to prevent mother-to-child transmission of HIV infection

(signed by the child's legal representative)

I, ________________________________________________________________ (Full name in block letters)

hereby confirm my voluntary consent to the treatment of the child

__________________________________________________________________ (Full name in block letters)

________________________ (date of birth) with medicinal products aimed at preventing the transmission of HIV infection from mother to child.

I confirm that I have been informed about:

- why this treatment is necessary for my child;

- the mechanism of action of the drugs prescribed to my child;

- how to properly administer the prescribed medications to my child;

- potential adverse effects of the drugs prescribed to my child;

- that my child must undergo regular examinations, including blood tests, to diagnose HIV infection, assess the safety of the prescribed treatment, and detect potential adverse drug reactions;

- the schedule for bringing my child in for examinations;

- that the preventive effect can only be achieved with strict adherence to all recommendations given to me by the attending physician.

I realize that:

- in the absence of chemoprophylaxis for mother-to-child transmission of HIV, the probability of infection is up to 40%;

- the administration of antiretroviral drugs (according to the ATC classification: systemic antivirals) reduces the probability of HIV infection in the child to 1%;

- if treatment poses a threat to my child's health, I will be informed to make a decision on the advisability of its continuation;

- if treatment poses a threat to my child's life, it may be discontinued by decision of the attending physician. In this case, the reasons for this decision must be explained to me;

- all medicinal products prescribed to my child are approved for use in Russia;

- like any medicinal product, the drugs prescribed to my child may cause certain adverse reactions, information about which has been provided to me by my attending physician.

I undertake to:

- bring my child for medical examinations according to the established schedule to monitor the effects of the prescribed medications, complete the provided questionnaires, and give consent for blood sampling for tests;

- administer the medications prescribed to my child strictly in accordance with the attending physician's instructions;

- follow the attending physician's recommendations regarding the care and feeding of my child;

- not put the child to the breast or feed them with my breast milk;

- inform the attending physician about any lapses in administering the prescribed medications to my child or discontinuation of treatment for any reason;

- inform the attending physician about any changes in my child's health status immediately (within 24 hours) if I believe these changes are related to the medications prescribed to my child;

- not give my child any medications or vaccinations without consulting the attending physician (even if the medications and vaccinations are prescribed by another doctor). If taking such medications is unavoidable (e.g., in emergency cases), inform the attending physician immediately;

- inform the doctor who prescribed medications to my child in an emergency case that the child is receiving drugs for the prevention of HIV infection.

Signature of the child's legal representative: ________________ Date: ________________

Signature of the attending physician ____________________________ Date: _________________

Appendix A3.11. Notice of liability for refusing prevention of transmission

Notice of liability for refusing the prevention of mother-to-child transmission of HIV

I, _____________________________________________________________________ born on _________, (Full name) have been informed of the medical and legal consequences of refusing mother-to-child transmission prophylaxis for my own health and the health of my child. The probability of HIV transmission from mother to child without preventive measures is up to 40%.

Regular intake of antiretroviral drugs by me reduces the risk of HIV transmission from mother to child to 1%.

Such reduction can be achieved by combining antiretroviral therapy during pregnancy, childbirth, and the postpartum period with a number of non-pharmacological measures, including complete replacement of breastfeeding with formula feeding.

Refusal to take antiretroviral drugs may lead to deterioration of health, disease progression, marked immunosuppression, and the development of severe, life-threatening opportunistic infections.

I have been informed that in the event of breastfeeding and refusal of antiretroviral therapy for the child, there is an immediate threat to the life and health of my child, consisting of the possibility of contracting HIV infection.

I have been informed that in this case, in accordance with Part 5 of Article 20 of Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation," if parents refuse medical care necessary to save a child's life, the medical organization has the right to apply to court to protect the child's interests.

According to the Family Code, the medical organization is obliged to notify the guardianship and trusteeship authorities, transferring my personal data for further action to protect the rights of the child in accordance with current legislation.

Articles of the Criminal and Family Codes and the Federal Law on the Fundamentals of Health Protection of Citizens were read aloud to me.

Patient signature ______________________ Date: __________________________

Signature of the attending physician ______________________ Date: __________________________

Signature of the head of department ______________________ Date: _______________________

(Full name, legibly) (signature)

Appendix A3.12. Measures to prevent refusals by HIV-infected women to undergo prevention of mother-to-child HIV transmission

1. Refusal by women to undergo prevention of mother-to-child transmission of HIV is caused by AIDS-denialist information in the media, denial of their HIV status (sometimes jointly with an HIV-infected partner), and fear of developing side effects from medication.

2. To ensure the timely protection of the child's rights to life and health, women are asked to sign a consent for the transfer of information constituting medical confidentiality in the prescribed manner to other medical organizations, guardianship, trusteeship, and patronage authorities in order to ensure the child's rights and legitimate interests.

3. If a refusal occurs, it is recommended:

   - consultation of the patient by the maximum possible number of physicians, a psychologist, a social worker, and a legal advisor, with documentation of the explanatory work in the medical records;

   - inviting the woman for repeat visits.

4. The woman must be warned about liability for refusing medical care that poses a threat to the life or health of a minor, with this recorded in the medical documentation (Articles 125 and 156 of the Criminal Code of the Russian Federation, Part 5, Article 20 of Federal Law No. 323-FZ dated November 21, 2011, "On the Fundamentals of Protecting the Health of Citizens in the Russian Federation").

5. It is recommended to fill out the notification form regarding liability for refusing the prevention of mother-to-child transmission of HIV (Appendix A3.9.). If the mother refuses to sign it, the document is read aloud to the mother and certified by the signatures of two medical workers.

6. Medical institutions must obligatorily inform guardianship and trusteeship authorities about mothers who refuse to carry out prevention for the child (at the child's actual location) (Part 3, Article 56 of the Family Code of the Russian Federation).

7. In exceptional cases (refusal of prevention for a newborn), guardianship and trusteeship authorities may apply Article 77 of the Family Code of the Russian Federation on the removal of a child in the event of an immediate threat to their health in order to organize further actions to protect the child's health.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

After diagnosing HIV infection, a discussion is held with the pregnant woman regarding the disease, its prognosis, impact on pregnancy and the health of the unborn child, and the proposed treatment regimen. The discussion is conducted in a format accessible to her, involving a psychologist if necessary. The necessity of prescribing ART no later than the 13th week of pregnancy, and subsequently during labor and for the newborn child to prevent perinatal transmission of HIV, is explained.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Questionnaire for determining risk factors for non-adherence in patients with HIV infection

Title in Russian: Questionnaire for determining risk factors for non-adherence in patients with HIV infection.

Source: Fedyaeva O.N., Sirota N.A. Risk factors for non-adherence to antiretroviral therapy in patients with HIV infection and methods for their identification. Meditsinskiy Sovet. 2014;(7):77-79.

Type (underline):

rating scale

index

questionnaire

other (specify)

Purpose: to determine risk factors for ART non-adherence in patients with HIV infection

Content and interpretation:

Appendix G2. Sheehan Anxiety Scale

Russian title: Sheehan Patient-Rated Anxiety Scale

Original title: Sheehan Patient-Rated Anxiety Scale - (SPRAS),

(David V. Sheehan, 1983).

Source: Sheehan D.V., Sheehan Kr. // Int. J. Psychiat. Med, - 1983. - N 12. - P. 243-266.

Type (underline):

rating scale

index

questionnaire

other (specify):

Purpose: for screening diagnostics and self-diagnostics of anxiety spectrum disorders in adults.

Content (template): determine how much the symptoms listed below have bothered you over the past week. Mark the number of your answer on the answer sheet.

Key (interpretation):

The total score on the scale is equal to the sum of the scores of all items. Thus, the total score can range from 0 to 140.

0-29 - absence of clinically significant anxiety, 30-79 - clinically significant anxiety, 80 and above - severe anxiety disorder, panic disorder.