HIV in Women

Hopkins HIV Report 2006 Mar; 18(2):7,11

Brenda Ross, M.D.
Johns Hopkins

This year’s meeting offered a broad smattering of topics directly relevant to health care practitioners serving HIV-infected women, whether they are based in resource poor settings or wealthier nations. This is a limited summary of some of the highlights.

Survival of Women

Monica Gandhi gave a well organized and comprehensive presentation that systematically reviewed data on HIV outcomes in men and women along several parameters, including response to therapy, adverse effects and disease progression in the HAART era [Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 116]. Although women initially have lower viral loads than men, survival rates in both sexes are similar in studies that control for access to HAART and socioeconomic factors.

Genital Lesions and HIV Transmission

Perhaps the roster of known risk factors for acquisition of HIV infection among women in endemic areas should be expanded to include genital schistosomiasis. As noted by Eyrun Kjetland, the worldwide infection rate for schistosomiasis is approximately 1 in 30 adults, 85% of whom live in Africa [Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 34LBa]. In a cross-sectional study of 479 sexually active non-pregnant, non-menopausal women between the ages of 20-49 who were followed for one year, there was a significantly increased risk of HIV infection among women with genital schistosomiasis. Genital schistosomiasis is found in 65% of women with urinary schistosomiasis. It is associated with friable cervical lesions known as “sandy patches” that may bleed during intercourse, thereby facilitating viral access and HIV infection. The prevalence of HIV among women with genital schistosomiasis was 41% versus 26% among those without genital schistosomiasis. Although this is an observational study and thus inconclusive, the previously documented 3-6 fold increased rates of HIV transmission among patients with genital ulcers make these results biologically plausible. The frequency of genital schistosomiasis in some populations and its potential role in HIV acquisition calls to question the role that adequate treatment for schistosomiasis would play in thwarting the HIV epidemic. Additional studies are needed.

Male Circumcision

The role of male circumcision in promoting HIV acquisition in men and HIV transmission to women was an important highlight of this year’s meeting. In a plenary session Tom Quinn summarized observational studies and a recently completed randomized trial that provide convincing data that circumcised men are at lower risk for acquiring HIV infection than uncircumcised men [Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 120]. In an observational study based in Rakai, Uganda, the impact of circumcision on the rates of HIV and other sexually transmitted diseases (syphilis, HSV-2, HPV, gonorrhea, Chlamydia, Trichomonas vaginitis, and bacterial vaginosis) was assessed [Gray R, et al. Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 128]. In the prevalence analysis using 3,949 married couples, the rate of HIV in wives of circumcised men was 16.1% compared to 21.7% in the wives of uncircumcised men for a significant rate ratio of 0.74. The rates of Trichomonas vaginitis and bacterial vaginitis were also significantly higher among the wives of the uncircumcised HIV-infected men. Rates of HSV-2 and HPV were also higher but these differences were not significant. The rates of gonorrhea, Chlamydia, and syphilis were not associated with the circumcision status of the male partner. The authors then followed 44 HIV-uninfected women with circumcised HIV-infected husbands and 299 HIV-uninfected women with uncircumcised HIV-infected husbands. The incidence of HIV infection in the wives of circumcised HIV-infected men was higher than in the wives of the uncircumcised men, although this difference was not significant (6.6/100 person-years versus 10.3/100 person-years, IRR .64, p=0.22).

ANRS 1285 Trial

To determine the role of active genital HSV-2 lesions on genital HIV-1 viral shedding, a randomized clinical trial was conducted enrolling 140 HIV-1/HSV-2 co-infected women in Burkina Faso [Nagot N, et al. Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 33LB]. The women, who were not eligible for HAART, were randomized into two groups: group 1 was treated with valacyclovir suppression (1 g/day) for 3 months, and group 2 received a placebo. HIV-1 genital shedding, HSV-2 genital shedding, and HIV-1 plasma viral loads were monitored biweekly. HIV-1 and HSV-2 genital viral shedding were reduced among the women treated with valacyclovir. In addition, HIV-1 plasma viral loads were also significantly reduced among the patients on HSV suppressive therapy (-0.39 vs +0.12 log₁₀ c/mL, p<0.001). This may have important implications for the risk of transmission of both HSV-2 and HIV-1 to partners of co-infected women, as well as reaffirming the practicality of HSV suppression therapy in co-infected women during pregnancy.

Pregnancy and HIV

Mechanisms for Mother-to-Child Transmission (MTCT). Maternal screening for HIV and advances in therapeutic options have culminated in a dramatic reduction in the risk of perinatal HIV transmission. Earlier studies have demonstrated that the majority (70%) of congenitally infected neonates are infected intrapartum, with the remaining 30% being infected prior to the onset of labor (intrauterine). In an elegantly designed study, Elizabeth Russell and coworkers were able to elucidate distinct mechanisms for intrauterine versus intrapartum transmission [Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 124]. By amplifying a specific region of the HIV env gene (highly variable V1/V2 region) and tracking the diversity of the viral population in maternal and newborn plasma samples, this group was able to demonstrate that intrauterine HIV infection results in transmission of fewer maternal viral variants, and notably, the transmitted virus most often represents the predominant circulating virus. In contrast, infants infected during the intrapartum period are more often infected with rare viral variants that represent compartmentalized or highly selected virus. Although we have made tremendous progress in reducing the risk of transmission, this study demonstrates that we have a lot to learn.

Repeat single dose Nevirapine in Subsequent Pregnancies

Single dose Nevirapine (sdNVP) effectively reduces the risk of MTCT of HIV. Efficacy, ease of administration, and low cost make this an attractive regimen. However, high rates of maternal resistance following a single exposure, over 40% in some studies, left many questioning its efficacy in subsequent pregnancies and the legitimacy of its role as a first-line agent in many resource poor settings. Eure and colleagues sought to answer this question [Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 125]. There were retrospective and prospective components to this trial.

The retrospective study compared Ugandan women who had received sdNVP in the HIVNET 012 trial and who had received the same treatment during a subsequent pregnancy with a control group of women who were treated with AZT in the HIVNET 012 trial and sdNVP in the subsequent pregnancy. The prospective component compared a group of pregnant women with prior sdNVP exposure to a group of NVP-naïve pregnant women. There were 198 mother infant pairs. The infants were followed for 6 weeks. The interim analysis showed no statistical difference in the rates of vertical transmission between the sdNVP exposed and the NVP-naïve groups. Long-term follow-up of the infants continues.

Cotrimoxazole and Birth Outcomes

HIV-infected women with advanced disease, particularly in resource poor settings, may be at greater risk for poor pregnancy outcomes including preterm delivery, fetal growth restriction and neonatal mortality. Jan Walter and collaborators sought to examine the likelihood of improved fetal outcomes among HIV infected women in Zambia treated with cotrimoxazole during pregnancy [Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 126]. In this group of women with CD4 counts <200 cells/mm³ who were not on antiretrovirals, there was a reduction in the incidence of chorioamnionitis, prematurity and neonatal mortality. Though this has implications in settings where access to ART is limited, the extrapolation of these results to women on HAART would be inappropriate.

2006-03-10
HHR-2006-03-04

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