Characteristics of the Course and Outcomes of Pregnancy in HIV-Infected Women against the Background of Associated Herpetic Infection

The dissertation is devoted to the study of the characteristics of the course and outcomes of pregnancy in women with HIV infection against the background of concomitant herpetic infections caused by herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The research encompasses the clinical-immunological aspects of the course of pregnancy, childbirth, and the postpartum period, as well as issues of perinatal transmission of herpesviruses to newborns. Special attention is given to the influence of active and latent forms of associated herpetic infections on the frequency of complications, the level of HIV viral load, and the state of T-cell immunity.

The work evaluates the effectiveness of chemoprophylaxis of perinatal HIV transmission and the impact of the mode of delivery on the frequency of vertical transmission of herpesviruses. The obtained data have been used to substantiate the management strategy for pregnant women with HIV infection and associated herpetic infections, including the timing of preventive measures and the choice of delivery method.

RELEVANCE OF THE TOPIC

As of January 1, 2006, 347,704 cases of HIV infection were registered in the Russian Federation [Pokrovsky V.V., 2006], of which one third pertains to women of reproductive age, and accordingly the number of HIV-infected pregnant women is increasing. Thus, in 2002–2004, the percentage of pregnant women among HIV-infected individuals amounted to 3.6–5.1%. Furthermore, over the past few years, a trend toward conscious continuation of pregnancy has been observed among women with HIV infection (from 31.8% in 2002 to 34.5% in 2004) [Rakhmanova A.G., 2005].

A condition for the physiological course of pregnancy is the alteration of the immune reactivity of the woman's body, which develops under the influence of both the internal environment of the organism itself and the cellular and humoral factors of the fetus [Sevostyanova O.S., 2001].

The human immunodeficiency virus is a pathogen that directly targets the human immune system. By acting on immune cells, the virus impedes the development of a normal immune response, leading to pronounced suppression of the immune system and subsequently contributing to the development of various opportunistic infections [Mitin Yu.A., 1997; Pokrovsky V.V., 2002]. Pregnant women with HIV infection constitute a risk group with respect to various infectious complications during pregnancy, childbirth, and the postpartum period [Suleeva S.V., 2000; Rakhmanova A.G., 2001].

Numerous studies have shown that in HIV-infected women, the structure of associated infections frequently includes infection with herpes group viruses (Epstein-Barr virus, herpes simplex virus, cytomegalovirus, varicella-zoster virus), as well as hepatitis B and C viruses [Kuzmin V.N.; Serov V.N., 2000; Mege O.S., 1998]. HIV affects the clinical manifestations of associated infections, which in turn affect HIV replication and may accelerate disease progression [Belozers E.S., 1999; Lobzin Yu.V., 2000]. It is known that herpes simplex viruses can activate the HIV genome in the proviral stage and are cofactors in the progression of HIV infection to AIDS [Kuzmenko T.N., 2000]. Moreover, in the context of HIV infection, these associated infections are in many cases more aggressive, more difficult to treat, and prone to recurrence [Lysenko A.Ya., 2001].

Currently, there are data indicating that most complications during pregnancy (non-carrying, polyhydramnios), during childbirth (premature rupture of membranes, placental attachment anomalies) in HIV-infected women, as well as neonatal pathologies (prematurity, asphyxia, fetal hypotrophy), may be attributable to the direct influence of associated infections of different etiologies [Friese K.; Kachel W., 2004].

Nevertheless, scattered reports do not allow an assessment of the impact of herpes group viruses on the course of pregnancy, childbirth, and the postpartum period in HIV-infected women. Data are lacking on the frequency of perinatal transmission of herpesviruses to newborns from HIV-infected mothers with active and latent forms of associated herpetic infections. The management strategy for pregnancy and childbirth in HIV-infected women against the background of associated herpesvirus infections, aimed at reducing the frequency of their perinatal transmission to newborns, remains insufficiently developed.

OBJECTIVE OF THE STUDY

To identify the characteristics of the course and outcomes of pregnancy in HIV-infected women against the background of associated herpetic infections (herpes simplex virus, cytomegalovirus, Epstein-Barr virus).

RESEARCH OBJECTIVES:

1. To determine the frequency of combinations of HIV infection and active forms of associated herpetic infections (herpes simplex virus, cytomegalovirus, Epstein-Barr virus) during pregnancy, childbirth, and the postpartum period.

2. To evaluate the characteristics of the course of pregnancy, childbirth, and the postpartum period in HIV-infected women against the background of associated herpetic infections manifesting in active and latent forms.

3. To identify the characteristics of the clinical course of associated herpesvirus infections during pregnancy in HIV-infected individuals depending on the level of HIV viral load.

4. To determine the state of the T-cell immune system and the level of HIV viral load in HIV-infected pregnant women with active and latent forms of associated herpetic infections.

5. To study the frequency of transmission of herpesviruses (herpes simplex virus, cytomegalovirus, Epstein-Barr virus) to newborns from HIV-infected mothers with active and latent forms of associated herpetic infections depending on the state of immunity and the level of HIV viral load.

6. To evaluate the impact of chemoprophylaxis of perinatal HIV transmission and the mode of delivery on the frequency of herpesvirus transmission to newborns.

SCIENTIFIC NOVELTY

For the first time, an analysis of the characteristics of the course of pregnancy, childbirth, and the postpartum period in HIV-infected women with associated herpetic infections (AHI) has been conducted. A reliable influence of active forms of AHI on the development of such pregnancy and childbirth complications as threat of pregnancy termination, polyhydramnios, premature rupture of membranes, labor anomalies, and placental attachment anomalies has been established. A reliable correlational relationship between the activation of AHI in HIV-infected women and the occurrence of threat of pregnancy termination has been identified.

The frequency of replicative forms of AHI and their combinations in mixed infection in HIV-infected women has been established, with an assessment of major T-cell immune system indicators, as well as the level of HIV viral load during pregnancy, childbirth, and the postpartum period.

The frequency of transmission of herpesvirus infection markers (herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)) to newborns from HIV-infected mothers depending on the mode of delivery, as well as the timing of chemoprophylaxis of vertical HIV transmission, has been determined.

PRACTICAL SIGNIFICANCE

In HIV-infected pregnant women with active forms of AHI, the necessity of chemoprophylaxis of perinatal HIV transmission beginning from the second trimester of pregnancy has been substantiated, which allows for the most effective reduction in the frequency of herpesvirus transmission to newborns. When determining the mode of delivery in HIV-infected women with active forms of AHI with an HIV viral load exceeding 10,000 copies of HIV RNA per 1 mL of plasma, cesarean section is the optimal method.

The diagnostic value of immunological examination and determination of viral load in HIV-infected women with active forms of AHI at various stages of pregnancy has been demonstrated. It has been established that monitoring the HIV viral load throughout pregnancy is the most informative indicator for predicting the severity of the course of active forms of AHI, the risk of their vertical transmission, and for determining the scope of chemoprophylaxis of perinatal HIV transmission.

DEFENDABLE POSITIONS

1. In HIV-infected pregnant women, associated herpetic infections (pathogens of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus) are reliably more frequently in a state of replicative activity than in a latent form. Replicative activity of a single herpesvirus is most commonly observed.

2. The risk of pregnancy complications and childbirth outcomes in HIV-infected women with associated herpetic infections (AHI) depends on the replicative activity of the causative agents of these infections. Active forms of AHI cause a greater frequency of pregnancy and childbirth complications compared to HIV-infected pregnant women with latent forms of herpesvirus infections.

3. In HIV-infected women with AHI in active form, a direct correlational relationship has been established between the magnitude of viral load (at the time of delivery) and the detection of herpesvirus markers in newborns.

4. The frequency of vertical transmission of herpesviruses from HIV-infected mothers with active forms of AHI depends on the mode of delivery. Delivery by cesarean section resulted in a reliably lower frequency of herpesvirus transmission to the child compared to delivery through the natural birth canal. Initiation of chemoprophylaxis of vertical HIV transmission from the second trimester of pregnancy most effectively reduces the frequency of herpesvirus transmission to the newborn.

APPROVAL OF THE WORK AND IMPLEMENTATION OF RESULTS IN PRACTICE

The dissertation materials have been presented at the international scientific-practical conference "Health of the Young" (St. Petersburg, 2005), at a joint inter-departmental meeting of the Departments of Obstetrics and Gynecology and Infectious Diseases of the Medical Faculty of St. Petersburg State University (June 7, 2006). The research results have been implemented in the practical work of the obstetric department of City Infectious Hospital No. 30 named after S.P. Botkin, as well as in the St. Petersburg City Center for the Prevention and Control of AIDS and Infectious Diseases.

Based on the dissertation materials, 5 scientific works have been published.

LIST OF WORKS PUBLISHED ON THE TOPIC OF THE DISSERTATION:

1. Frequency of associated viral infections in HIV-positive women depending on the degree of viral load // Proceedings of the International Congress "Euro-Asian Congress" — St. Petersburg, 2004 — P. 21–22 — (co-authors: Niauri D.A., Yakovlev A.A.).

2. Study of the frequency of herpesvirus and papillomavirus transmission to children in HIV-infected women depending on the mode of delivery. // Almanac "Infectious Diseases-2003" St. Petersburg, 2004 — P. 159–161 — (co-authors: Niauri D.A., Yakovlev A.A.).

3. Study of the influence of combined herpesvirus and papillomavirus infections on the course and outcomes of pregnancy in HIV-infected women // Congress of Young Scientists — St. Petersburg. Military Medical Academy named after S.M. Kirov., 2004 — P. 57 — (co-authors: Niauri D.A., Yakovlev A.A.).

4. Characteristics of the clinical course of associated herpesvirus and papillomavirus infections in HIV-infected women // Collection "Health of the Young" — St. Petersburg, 2005 — P. 26–27 — (co-authors: Niauri D.A., Yakovlev A.A.).

5. Characteristics of the course and outcomes of pregnancy in HIV-infected women against the background of associated herpetic infection // Vestnik of St. Petersburg University. Series 11, 2007, Issue 1, P. 108–113 — (co-authors: Niauri D.A., Yakovlev A.A.).

SCOPE AND STRUCTURE OF THE DISSERTATION:

The dissertation comprises 135 pages of printed text and consists of an introduction, a literature review, a description of materials and research methods, six chapters of original research, a discussion of the results obtained, conclusions, practical recommendations, and a list of references comprising 277 literary sources: 99 by domestic and 178 by foreign authors. The work contains 29 tables and 2 figures.