HIV in pregnancy is a chronic progressive infectious disease caused by a pathogen from the group of retroviruses and occurred before conception of a child or in the gestational period. It is latent for a long time. The primary reaction is manifested by hyperthermia, skin rash, mucosal lesions, transient enlargement of lymph nodes, diarrhea. Subsequently, generalized lymphadenopathy occurs, weight gradually decreases, HIV-associated disorders develop. It is diagnosed by laboratory methods (ELISA, PCR, cellular immunity study). Antiretroviral therapy is used for the treatment and prevention of vertical transmission.
HIV in pregnancy is a severe anthroponosis with a parenteral nontransmissive mechanism of infection from an infected person. Over the past 20 years, the number of newly infected pregnant women has increased almost 600 times and exceeded 120 per 100 thousand examined. The majority of women of childbearing age were sexually infected, the proportion of HIV-positive patients with drug addiction does not exceed 3%. Due to compliance with the rules of asepsis, sufficient antiseptic treatment of instruments for invasive procedures and effective serological control, it was possible to significantly reduce the frequency of infection as a result of occupational injuries, blood transfusions, due to the use of contaminated instruments and donor materials. In more than 15% of cases, it is not possible to reliably determine the source of the pathogen and the mechanism of infection. The urgency of special support for HIV-infected pregnant women is due to the high risk of fetal infection in the absence of adequate restraining treatment.
Causes of HIV in pregnancy
The causative agent of hiv in pregnancy is a human immunodeficiency retrovirus of one of two known types — HIV-1 (HIV-1) or HIV-2 (HIV-2), represented by many subtypes. Usually, infection occurs before the beginning of pregnancy, less often — at the time or after conception of the child, during gestation, childbirth, and the postpartum period. The most common route of transmission of an infectious agent in pregnant women is natural (sexual) through the mucosal secretions of an infected partner. Infection is possible with intravenous administration of narcotic drugs, violation of aseptic and antiseptic norms during invasive manipulations, performance of professional duties with the possibility of contact with the blood of the carrier or patient (medical workers, paramedics, cosmetologists). During pregnancy, the role of some artificial parenteral infection pathways increases, and they themselves acquire a certain specificity:
- Hemotransfusion infection. With a complicated course of pregnancy, childbirth and the postpartum period, the probability of blood loss increases. Treatment regimens for the most severe bleeding involve the introduction of donor blood and drugs derived from it (plasma, erythrocyte mass). HIV infection is possible when using virus-tested material from an infected donor in the case of blood sampling during the so-called seronegative incubation window, lasting from 1 week to 3-5 months from the moment the virus enters the body.
- Instrumental infection. Invasive diagnostic and therapeutic procedures are prescribed to pregnant patients more often than non-pregnant ones. To exclude fetal abnormalities, amnioscopy, amniocentesis, chorion biopsy, cordocentesis, placentocentesis are used. For diagnostic purposes, endoscopic examinations (laparoscopy) are performed, for therapeutic purposes — suturing of the cervix, fetoscopic and fetal drainage operations. Infection through contaminated instruments is possible during childbirth (when suturing injuries) and during cesarean section.
- The transplantation pathway of virus transmission. Possible solutions for couples planning pregnancy with severe forms of male infertility are insemination with donor sperm or its use for IVF. As in cases with blood transfusions, in such situations there is a risk of infection when using infected material obtained during the seronegative period. Therefore, for preventive purposes, it is recommended to use the sperm of donors who successfully passed an HIV test six months after the delivery of the material.
The spread of HIV through the body occurs with blood and macrophages, into which the pathogen is initially introduced. The virus has a high tropicity to target cells whose membranes contain a specific CD4 protein receptor – T—lymphocytes, dendritic lymphocytes, parts of monocytes and B-lymphocytes, resident microphages, eosinophils, cells of the bone marrow, nervous system, intestines, muscles, vascular endothelium, choriontrofoblast of the placenta, possibly spermatozoa. After replication, a new generation of the pathogen leaves the infected cell, destroying it.
Immunodeficiency viruses have the greatest cytotoxic effect on type I T4 lymphocytes, which leads to depletion of the cell population and disruption of immune homeostasis. A progressive decrease in immunity worsens the protective characteristics of the skin and mucous membranes, reduces the effectiveness of inflammatory reactions to the penetration of infectious agents. As a result, in the final stages of the disease, the patient develops opportunistic infections caused by viruses, bacteria, fungi, helminths, protozoal flora, tumors typical of AIDS (non-Hodgkin’s lymphomas, Kaposi’s sarcoma), autoimmune processes begin, eventually leading to the death of the patient.
Domestic virologists use in their work the systematization of the stages of HIV infection proposed by V. Pokrovsky. It is based on the criteria of seropositivity, the severity of symptoms, the presence of complications. The proposed classification reflects the gradual development of infection from the moment of infection to the final clinical outcome:
- Incubation stage. HIV is present in the human body, its active replication occurs, but antibodies are not detected, there are no signs of an acute infectious process. The duration of seronegative incubation usually ranges from 3 to 12 weeks, while the patient is contagious.
- Early HIV infection. The primary inflammatory response of the body to the spread of the pathogen lasts from 5 to 44 days (in half of the patients — 1-2 weeks). In 10-50% of cases, the infection immediately takes the form of an asymptomatic carrier, which is considered a more prognostically favorable sign.
- The stage of subclinical manifestations. Virus replication and destruction of CD4 cells lead to a gradual increase in immunodeficiency. Generalized lymphadenopathy becomes a characteristic manifestation. The latent period in HIV infection lasts from 2 to 20 years or more (on average – 6-7 years).
- The stage of secondary pathology. Depletion of protective forces is manifested by secondary (opportunistic) infections, oncopathology. The most common AIDS-indicator diseases in Russia are tuberculosis, cytomegalovirus and candida infections, pneumocystis pneumonia, toxoplasmosis, Kaposi’s sarcoma.
- Terminal stage. Against the background of severe immunodeficiency, pronounced cachexia is noted, there is no effect from the therapy used, the course of secondary diseases becomes irreversible. The duration of the final stage of HIV infection before the death of the patient is usually no more than a few months.
Practicing obstetricians and gynecologists often have to provide specialized care to pregnant women who are in the incubation period, at an early stage of HIV infection or its subclinical stage, less often – with the appearance of secondary disorders. Understanding the features of the disease at each stage allows you to choose the optimal pregnancy management scheme and the most appropriate method of delivery.
Since during pregnancy, the I-III stages of the disease are determined in most patients, pathological clinical signs are absent or look nonspecific. During the first three months after infection, 50-90% of infected people have an early acute immune reaction, which is manifested by weakness, a slight increase in temperature, urticaria, petechial, papular rash, inflammation of the mucous membranes of the nasopharynx, vagina. Some pregnant women have enlarged lymph nodes, diarrhea develops. With a significant decrease in immunity, short-term, mild candidiasis, herpes infection, and other intercurrent diseases may occur.
If HIV infection occurred before pregnancy, and the infection developed to the stage of latent subclinical manifestations, the only sign of the infectious process is persistent generalized lymphadenopathy. A pregnant woman has at least two lymph nodes with a diameter of 1.0 cm, located in two or more groups that are not interconnected. When touched, the affected lymph nodes are elastic, painless, not connected to the surrounding tissues, the skin above them has an unchanged appearance. The increase in nodes persists for 3 months or more. Symptoms of secondary pathology associated with HIV infection are rarely detected in pregnant women.
The most serious consequence of pregnancy of an HIV-infected woman is perinatal (vertical) infection of the fetus. Without adequate restraining therapy, the probability of infecting a child reaches 30-60%. In 25-30% of cases, the immunodeficiency virus gets from mother to child through the placenta, in 70-75% — during childbirth when passing through infected birth canal, in 5-20% — through breast milk. HIV infection in 80% of perinatally infected children develops rapidly, and AIDS symptoms occur within 5 years. The most characteristic signs of the disease are hypotrophy, persistent diarrhea, lymphadenopathy, hepatosplenomegaly, developmental delay.
Intrauterine infection often leads to damage to the nervous system — diffuse encephalopathy, microcephaly, cerebellar atrophy, deposition of intracranial calcifications. The probability of perinatal infection increases with acute manifestations of HIV infection with high viremia, a significant deficiency of T-helpers, extragenital diseases of the mother (diabetes mellitus, cardiopathology, kidney diseases), the presence of sexually transmitted infections in the pregnant woman, chorioamnionitis. According to the observations of specialists in the field of obstetrics, patients infected with HIV are more likely to experience the threat of termination of pregnancy, spontaneous miscarriages, premature birth, and increased perinatal mortality.
Taking into account the potential danger of the patient’s HIV status for the unborn child and the medical staff, the immunodeficiency virus test is included in the list of recommended routine examinations during pregnancy. The main tasks of the diagnostic stage are to identify possible infection and determine the stage of the disease, the nature of its course, and prognosis. Laboratory research methods are the most informative for making a diagnosis:
- Enzyme immunoassay. It is used as a screening. It allows detecting antibodies to the human immunodeficiency virus in the blood serum of a pregnant woman. In the seronegative period, it is negative. It is considered a method of preliminary diagnosis, requires confirmation of the specificity of the results.
- Immune blotting. The method is a kind of ELISA, makes it possible to determine antibodies in serum to certain antigenic components of the pathogen distributed by molecular weight by foresis. It is the positive result of the immunoblot that serves as a reliable sign of the presence of HIV infection in a pregnant woman.
- PCR diagnostics. Polymerase chain reaction is considered a method of early detection of the pathogen with an infection period of 11-15 days. With its help, viral particles are detected in the patient’s serum. The reliability of the technique reaches 80%. Its advantage is the possibility of quantitative control of HIV RNA copies in the blood.
- Study of the main subpopulations of lymphocytes. The probable development of immunosuppression is indicated by a decrease in the level of CD4 lymphocytes (T-helper cells) to 500/ ml or less. The immunoregulatory index showing the ratio between T-helpers and T-suppressors (CD8 lymphocytes) is less than 1.8.
Upon admission to childbirth of a previously untreated pregnant woman from marginal contingents, it is possible to conduct an express HIV test using highly sensitive immunochromatographic test systems. Noninvasive diagnostic methods (transabdominal ultrasound, dopplerography of uteroplacental blood flow, cardiotocography) are preferred for routine instrumental examination of an infected patient. Differential diagnosis at the stage of early reaction is carried out with acute respiratory viral infections, infectious mononucleosis, diphtheria, rubella, and other acute infections. If generalized lymphadenopathy is detected, it is necessary to exclude hyperthyroidism, brucellosis, viral hepatitis, syphilis, tularemia, amyloidosis, lupus erythematosus, rheumatoid arthritis, lymphoma, other systemic and oncological diseases. According to the indications, the patient is consulted by an infectious disease specialist, dermatologist, oncologist, endocrinologist, rheumatologist, hematologist.
Treatment of HIV in pregnancy
The main tasks of pregnancy management in case of infection with the human immunodeficiency virus are infection suppression, correction of clinical manifestations, prevention of infection of the child. Depending on the severity of symptoms and the stage of the disease, massive polytropic therapy with antiretroviral drugs is prescribed — nucleoside and non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors. The recommended treatment regimens differ at different gestation periods:
- When planning a pregnancy. In order to avoid an embryotoxic effect, women with HIV-positive status should stop taking special medications before the onset of the fertile ovulatory cycle. In this case, it is possible to completely eliminate teratogenic effects in the early stages of embryogenesis.
- Up to 13 weeks of pregnancy. Antiretroviral drugs are used in the presence of secondary diseases, a viral load exceeding 100 thousand copies of RNA / ml, a decrease in the concentration of T-helper cells less than 100 / ml. In other cases, pharmacotherapy is recommended to be discontinued to exclude negative effects on the fetus.
- From 13 to 28 weeks. When HIV infection is diagnosed in the second trimester or an infected patient is treated at this time, active retroviral therapy is urgently prescribed with a combination of three drugs – two nucleoside reverse transcriptase inhibitors and one drug from other groups.
- From 28 weeks before delivery. Anti-retroviral treatment continues, chemoprophylaxis of transmission of the virus from a woman to a child is being carried out. The most popular scheme is in which from the beginning of the 28th week a pregnant woman constantly takes zidovudine, and before giving birth once – nevirapine. In some cases, backup schemes are used.
The preferred method of delivery in a pregnant woman with a diagnosed HIV infection is natural childbirth. During their implementation, it is necessary to exclude any manipulations that violate the integrity of tissues — amniotomy, episiotomy, the imposition of obstetric forceps, the use of a vacuum extractor. Due to a significant increase in the risk of infection of the child, the use of drugs that cause and enhance labor activity is prohibited. Cesarean section is performed after 38 weeks of gestational age with unknown indicators of viral load, its level of more than 1,000 copies / ml, the absence of prenatal antiretroviral therapy and the inability to administer retrovir in childbirth. In the postpartum period, the patient continues taking the recommended antiviral drugs. Since breastfeeding is prohibited, lactation is suppressed by medication.
Prognosis and prevention
Adequate prevention of HIV transmission from the pregnant woman to the fetus can reduce the level of perinatal infection to 8% or less. In economically developed countries, this figure does not exceed 1-2%. Primary prevention of infection involves the use of barrier contraceptives, sex life with a regular trusted partner, refusal to inject drugs, the use of sterile instruments when performing invasive procedures, careful monitoring of donor materials. To prevent infection of the fetus, timely registration of an HIV-infected pregnant woman in a women’s clinic, refusal of invasive prenatal diagnosis, selection of the optimal scheme of antiretroviral treatment and method of delivery, prohibition of breastfeeding are important.