Effect of Pregnancy and Zidovudine Therapy on Viral Load in HIV-1-Infected Women

Abstract

The objective of this study was to determine the effect of pregnancy and zidovudine (ZDV) on viral load in HIV-1 infected women. A prospective nonrandomized cohort study was conducted at a university medical center and affiliated clinic and included 44 HIV-1-seropositive pregnant women seen between June 1991 and September 1995. Twenty-three women initiated ZDV therapy during their pregnancy. Seventeen women did not take antiretrovirals, and four women took ZDV prior to and throughout pregnancy. HIV-1 viral load as determined by quantitative peripheral blood mononuclear cell (PBMC) culture and quantitative plasma RNA levels was measured at various times during pregnancy and in the postpartum period. HIV-1 load, by both infectivity and RNA levels, was relatively low and remained stable during pregnancy and through 6 weeks post partum. Initiation of ZDV therapy during pregnancy did not result in a significant decrease in viral load at delivery when controlling for the effect of pregnancy. In those women who received ZDV therapy only during pregnancy, there was a trend toward an increase in viral load measured by PBMC infectivity 6 months post partum compared with the levels before the initiation of ZDV. Mother-to-child transmission of HIV-1 occurred in one of 27 (4%) ZDV-treated women and in two of 16 (12.5%) untreated women. Among HIV-1-infected pregnant women with low viral levels, HIV-1 plasma RNA and infectivity remained stable during and after gestation. Although these results are based on a relatively small number of women and should be considered preliminary, the lack of significant ZDV-associated diminution in viral levels suggests that the protective effect of ZDV on the mother-to-child transmission of HIV-1 may not be due to the reduction in maternal viral levels but, by inference, may be due to the prevention of HIV-1 reverse transcription in the newborn.

Prophylactic and Therapeutic Benefits of Short-Term 9-[2-( R )-(Phosphonomethoxy)Propyl]Adenine (PMPA) Administration to Newborn Macaques following Oral Inoculation with Simian Immunodeficiency Virus with Reduced Susceptibility to PMPA

“…Because ZDV therapy has little effect on maternal virus levels and ZDV is effective in reducing transmission regardless of the maternal HIV-1 RNA copy number in plasma, it is believed that a significant portion of the protection is due to chemoprophylaxis in the newborn following exposure to the virus, rather than to a reduction of virus levels in the maternal blood (3,12,27,28,38). Further evidence for this chemoprophylactic mechanism was provided by a recent study in Uganda which demonstrated that the rate of perinatal HIV transmission was greatly reduced by administration of two doses of nevirapine, the first given to the mother in labor and the second given to the infant shortly after birth (16).…”

Postpartum changes in plasma viral load and CD4 percentage among HIV-infected women from Latin American and Caribbean countries: the NISDI Perinatal Study

“…First, in a retrospective study of HIV-infected women who discontinued ARVs at delivery (Tungsiripat et al 2007), median VLs at 12-96 weeks PP were similar to values obtained during pregnancy. In another study of 44 HIV-infected pregnant women, 23 women initiated ZDV therapy during pregnancy, 17 women did not use ARVs and four women used ZDV before and during pregnancy (Melvin et al 1997). Overall, VLs remained stable until six weeks PP, but there was a trend toward an increase in VL values PP among those women who received ZDV therapy only during pregnancy.…”

“…Similarly, other studies have assessed VL changes among HIV-infected women according to the continuation or discontinuation of ARVs after delivery (Cao et al 1997, Melvin et al 1997, Watts et al 2003, Martin et al 2006, Tungsiripat et al 2007. Some studies have suggested no change in VL PP, although others indicated VL increases.…”

“…The results of studies evaluating changes in the plasma HIV RNA concentration [viral load (VL)], the CD4 + lymphocyte percentage (CD4%) or absolute CD4 + lymphocyte count, or the HIV clinical disease stage in the postpartum (PP) period among HIV-infected women continuing or discontinuing ARVs after pregnancy have shown conflicting results (Cao et al 1997, Melvin et al 1997, Watts et al 2003, Martin et al 2006, Tungsiripat et al 2007, Cavallo et al 2010. To avoid the effect of a higher volume of distribution on absolute CD4 + lymphocyte counts, the CD4% should be used for monitoring T lymphocytes during pregnancy and PP (Miotti et al 1992, Ekouevi et al 2007).…”

Genetic Factors that Influence HIV Infection: The Role of the Major Histocompatibility Complex System

“…Treating HIV-infected pregnant women with the antiretroviral drug zidovudine was associated with a reduced rate of transmission (Connor et al, 1994), though the drug may not produce this effect by reducing viral load: a recent study found that zidovudine reduced vertical transmission despite a minimal effect on viral load (Melvin et al, 1997;Newberry and Kelsey, 2003). Whatever the mechanism of zidovudine, it remains generally true that risk of vertical transmission can be minimized if therapies known to reduce the patient's serum and vaginal viral loads are continued during pregnancy.…”