Pregnant Women and HIV

Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy

Study Question(s): This study was conducted by researchers from Ireland where pregnant women who do not need antiretroviral treatment (ART) for their health receive temporary triple combination therapy that is discontinued postpartum. What is the impact of temporary triple antiretroviral therapy in pregnancy on future antiretroviral resistance in women with HIV infection?

Study Participants: 50 pregnant women with HIV infection who had a CD4 cell count of greater than 300 before treatment. Most participants (92%) were from sub-Saharan Africa.

Study Methods: Participants started triple antiretroviral therapy in the third trimester of pregnancy and stopped after birth. Almost all women received zidovudine and lamivudine with either nelfinavir or nevirapine. One woman received didanosine, zidovudine and nevirapine. Eight women switched from nevirapine to nelfinavir for a variety of reasons. Genotypic resistance was tested after antiretrovirals were no longer being taken and on pretreatment samples when samples after birth showed primary mutations.

Study Findings: The amount of genotypic resistance in this group of pregnant women is significant. All mutations detected were in those that took nevirapine-containing regimens. The clinical implications of these mutations are unknown.

Limitations: Genotypic resistance testing was only done once. The small sample size may contribute to the inability to detect differences between those that developed mutations and those that did not. Adherence to therapy was not formally assessed.

Lessons Learned: This study suggests that the strategy of using triple antiretroviral therapy in pregnancy may not protect drugs with known low-genetic barriers such as nevirapine and the clinical implications of this remain to be seen.

Source: Lyons FE, Coughlan S, Byrne CM, Hopkins SM, Hall WW, Mulcahy FM. Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy. AIDS. 2005 Jan 3;19(1):63-7.

Risk Factors for HIV Transmission from Mother to Child

Study Question(s): What portion of HIV-infected children are infected during pregnancy (in utero) compared to those infected in delivery?

Study Participants: 1709 children with defined HIV infection from the Women and Infants Transmission Study between 1990 and 2000.

Study Methods: In utero HIV infection was defined as an infant with the first positive HIV test at 7 days of age or younger and intrapartum infection was defined as having a negative HIV test at 7 days of age or younger and the first positive test after 7 days of age.

Study Findings: Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection in 66%. Among infected children, the percent with in utero infection increased over time from 27% in 1990-1992 to 80% in 1999-2000. Maternal viral load before birth and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Low birth weight was significantly associated with in utero transmission, while age, CD4+ cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission.

Limitations: The authors assumed that those infants whose timing of transmission was not classifiable were infected in utero and during delivery in the same proportion as that observed among those who were classifiable. The distribution of age at the first positive HIV test does not separate clearly into two distinct intervals; therefore there is no natural cutoff to distinguish time of transmission, and some misclassification is inevitable. The number of women undergoing cesarean delivery was small in this study compared with other studies.

Lessons Learned: Although there have been significant declines in perinatal HIV infection over time, there has been an increase in the proportion of infections transmitted in utero. The timing of the first positive HIV test is often used to distinguish between in utero and intrapartum transmission. The study's results provide support for the accuracy of this approach to the classification of infants. These data also suggest that interventions to further reduce perinatal transmission in the United States include identification of maternal HIV infection before, or early in, pregnancy and the use of highly active antiretroviral combination therapy starting early in pregnancy to provide maximal suppression of viral replication.

Source: Magder LS, Mofenson L, Paul ME, Zorrilla CD, Blattner WA, Tuomala RE, LaRussa P, Landesman S, Rich KC. Risk factors for in utero and intrapartum transmission of HIV. J Acquir Immune Defic Syndr. 2005 Jan 1;38(1):87-95.