Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire. Safety of nevirapine-containing antiretroviral triple therapy regimens to prevent vertical transmission in an African cohort of HIV-1-infected pregnant women. Nevirapine-associated toxicity in HIV-infected Thai men and women, including pregnant women. Antiretroviral-associated toxicity among HIV-1-seropositive pregnant women in Mozambique receiving nevirapine-based regimens. Antiretroviral treatment and prevention of peripartum and postnatal HIV transmission in West Africa: evaluation of a two-tiered approach. HIV-1 persists in breast milk cells despite antiretroviral treatment to prevent mother-to-child transmission. Hematologic and hepatic toxicities associated with antenatal and postnatal exposure to maternal highly active antiretroviral therapy among infants.
Pregnancy outcomes in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described.
                HIV-1-infected pregnant women in the ANRS Ditrame Plus and the MTCT-Plus projects were included. Between March 2001 and July 2003, when HAART was not yet available, women eligible for HAART received a short-course antiretroviral regimen, zidovudine (ZDV) or (ZDV + lamivudine) and single dose of nevirapine for preventing mother-to-child transmission (PMTCT group). Between August 2003 and August 2007, eligible women for HAART received it (HAART group). The frequencies of low birth weight (LBW) (<2500 g), stillbirth and infant mortality are reported. Risk factors associated with LBW were investigated using a logistic regression model.
                Of the 326 HIV-infected pregnant women, 175 women received short-course antiretroviral (median CD4 cell count 177 cells/microl) and 151 received HAART (median CD4 cell count 182 cells/microl). At 12 months, three paediatric infections (2.3%) occurred in the HAART group vs. 25 (16.1%) in the PMTCT group (P < 0.001). The rate of LBW was 22.3% in the HAART group and 12.4% in the PMTCT group (P = 0.02). In multivariable analysis (n = 309), after adjustment on maternal CD4 cell count, WHO stage, age and maternal BMI, HAART initiated before pregnancy [adjusted odds ratio (OR) 2.88, 95% confidence interval (CI) 1.10-7.51] and during pregnancy (adjusted OR 2.12, 95% CI 1.15-4.65) and maternal BMI at delivery (adjusted OR 2.43, 95% CI 1.20-4.91) were associated with LBW.
                HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW. To assess the incidence and consequences of adverse reactions among African HIV-positive pregnant women treated with fixed-dose combinations of a nevirapine-containing antiretroviral (ARV) triple therapy.
                A retrospective analysis of the clinical files of 703 HIV-1-positive pregnant women treated with a nevirapine-containing regimen between May 2002 and July 2004 was conducted. Selection criteria for inclusion in the analysis were: (a) taking ARV for more than 14 days; (b) baseline values of transaminases below the threshold of 2.5 times the upper limit of normal (ULN). The women were on a nevirapine-containing regimen for a median of 127 days [interquartile range (IQR) 86-190 days], starting on average at the 27th week of gestation (standard deviation+/-9.5) and continuing up to a maximum of 6 months after delivery. All women were offered formula milk to feed the babies. Highly active antiretroviral therapy (HAART) was continued beyond 6 months only if the patient qualified on the first visit. The main outcome measures were incidence of hepatotoxicity, skin rashes and Stevens-Johnson syndrome. Multivariate analysis to assess the impact of several factors on the adverse reaction rate was performed.
                As of 1 August 2004, 554 pregnancies reached term, 96 women were still pregnant, and 53 women dropped out of the programme before giving birth. After 2 months of therapy the percentage of patients with a viral load less than 1000 HIV-1 RNA copies/mL increased to 78.6%; average CD4 cell counts increased from 490 cells/microL before therapy to 630 after therapy. The incidence of grade 3-4 adverse reactions (hepatotoxicity, skin rashes and Stevens-Johnson syndrome) was 6.5, 2.4 and 1.1%, respectively. Five women died during pregnancy (0.88%). Only one of the deaths could be associated with ARV treatment.
                Nevirapine-containing regimens in pregnant woman, at all CD4 cell count levels, appear to be safe in African settings. The aim of the study was to determine the incidence of, and risk factors for, nevirapine (NVP)-associated hepatotoxicity and rash in HIV-infected Thai men and women, including pregnant women, receiving NVP-containing highly active antiretroviral therapy (HAART).
                NVP-containing HAART was prescribed to eligible men and women enrolled in the Prevention of Mother-To-Child Transmission of HIV (PMTCT) and MTCT-Plus programmes. All pregnant women received zidovudine (ZDV)/lamivudine (3TC)/NVP from >14 weeks of gestational age if their CD4 cell count was <or=200 cells/microL or from >28 weeks if their CD4 cell count was >200 cells/microL. Patients followed for at least 8 weeks after starting HAART or until delivery were included in the analyses.
                Of 409 patients, 244 were pregnant women, 87 were nonpregnant women and 78 were men. Hepatotoxicity occurred in 15.6% of all patients. Men had a significantly higher rate of asymptomatic hepatotoxicity (P=0.021). Pregnant women receiving HAART for PMTCT (92% had CD4 cell counts >250 cells/microL) had a significantly higher rate of symptomatic hepatotoxicity (P=0.0003) than pregnant women receiving HAART for therapy. Rash occurred in 16.1% of all patients. The patients' sex and baseline CD4 cell count were not associated with the risk of hepatotoxicity or rash. NVP was discontinued in 4.2% and 6.8% of patients because of hepatotoxicity and rash, respectively.
                The incidence of NVP-related hepatotoxicity and rash in Thai adults is similar to incidences reported for other populations. While larger studies are needed, our data support continued use of NVP-containing regimens as first-line treatment in developing countries for HIV-infected patients, including pregnant women. Pregnant women with high CD4 cell counts may experience higher rates of symptomatic hepatotoxicity and thus require careful clinical and laboratory monitoring. To assess toxicities associated with highly active antiretroviral therapy (HAART) among HIV-1-infected pregnant women treated with nevirapine-based regimens according to Mozambican national guidelines.
                Prospective cohort study.
                HIV-1-infected antiretroviral-naive pregnant women with CD4 counts < or =350 cells/microL were initiated on nevirapine, lamivudine, and stavudine or zidovudine and followed monthly. Severe hepatotoxicity was defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels > or =5-fold the upper limit of normal. Analyses were stratified by baseline CD4 count (<250 vs. 250-350 cells/microL).
                Among 146 pregnant women, 75 (52%) began nevirapine, lamivudine, and zidovudine and 71 (48%) began nevirapine, lamivudine, and stavudine. Overall, 79 (54%) women had CD4 counts <250 cells/microL, 7 (5%) had grade II hepatotoxicity, and 4 (3%) had severe (grade III or IV) hepatotoxicity. All 4 women with severe hepatotoxicity had baseline CD4 counts > or =250 cells/microL (P = 0.02). Rates of skin toxicity, anemia, and peripheral neuropathy did not differ by CD4 cell count group. Overall, 12 (8%) women changed or discontinued HAART as a result of drug toxicity.
                Severe hepatotoxicity from nevirapine-containing HAART in this cohort of pregnant women was more common at higher CD4 counts (6% vs. 0% among women with CD4 counts > or =250 cells/microL and CD4 counts <250 cells/microL, respectively), suggesting that laboratory monitoring is necessary when administering nevirapine-containing regimens to pregnant women with CD4 counts > or =250 cells/microL. Highly active antiretroviral treatment (HAART) has only been recently recommended for HIV-infected pregnant women requiring treatment for their own health in resource-limited settings. However, there are few documented experiences from African countries. We evaluated the short-term (4 wk) and long-term (12 mo) effectiveness of a two-tiered strategy of prevention of mother-to-child transmission of HIV (PMTCT) in Africa: women meeting the eligibility criteria of the World Health Organization (WHO) received HAART, and women with less advanced HIV disease received short-course antiretroviral (scARV) PMTCT regimens.
                The MTCT-Plus Initiative is a multi-country, family-centred HIV care and treatment program for pregnant and postpartum women and their families. Pregnant women enrolled in Abidjan, Côte d'Ivoire received either HAART for their own health or short-course antiretroviral (scARV) PMTCT regimens according to their clinical and immunological status. Plasma HIV-RNA viral load (VL) was measured to diagnose peripartum infection when infants were 4 wk of age, and HIV final status was documented either by rapid antibody testing when infants were aged > or = 12 mo or by plasma VL earlier. The Kaplan-Meier method was used to estimate the rate of HIV transmission and HIV-free survival. Between August 2003 and June 2005, 107 women began HAART at a median of 30 wk of gestation, 102 of them with zidovudine (ZDV), lamivudine (3TC), and nevirapine (NVP) and they continued treatment postpartum; 143 other women received scARV for PMTCT, 103 of them with sc(ZDV+3TC) with single-dose NVP during labour. Most (75%) of the infants were breast-fed for a median of 5 mo. Overall, the rate of peripartum HIV transmission was 2.2% (95% confidence interval [CI] 0.3%-4.2%) and the cumulative rate at 12 mo was 5.7% (95% CI 2.5%-9.0%). The overall probability of infant death or infection with HIV was 4.3% (95% CI 1.7%-7.0%) at age week 4 wk and 11.7% (95% CI 7.5%-15.9%) at 12 mo.
                This two-tiered strategy appears to be safe and highly effective for short- and long-term PMTCT in resource-constrained settings. These results indicate a further benefit of access to HAART for pregnant women who need treatment for their own health. The effects of short-course antiretrovirals given to reduce mother-to-child transmission (MTCT) on temporal patterns of cell-associated HIV-1 RNA and DNA in breast milk are not well defined.
                Women in Kenya received short-course zidovudine (ZDV), single-dose nevirapine (sdNVP), combination ZDV/sdNVP or short-course highly active antiretroviral therapy (HAART). Breast milk samples were collected two to three times weekly for 4-6 weeks. HIV-1 DNA was quantified by real-time PCR. Cell-free and cell-associated RNA levels were quantified by the Gen-Probe HIV-1 viral load assay.
                Cell-free HIV-1 RNA levels in breast milk were significantly suppressed by sdNVP, ZDV/sdNVP or HAART therapy compared with ZDV between day 3 and week 4 postpartum (P < or = 0.03). Breast milk HIV-1 DNA levels (infected cell levels) were not significantly different between treatment arms at any timepoint during the 4-6-week follow-up. At 3 weeks postpartum, when the difference in cell-free RNA levels was the greatest comparing HAART directly with ZDV (P = 0.0001), median log10 HIV-1 DNA copies per 1 x 10 cells were 2.78, 2.54, 2.69, and 2.31 in the ZDV, sdNVP, ZDV/sdNVP and HAART arms, respectively (P = 0.23). Cell-associated HIV-1 RNA levels were modestly suppressed in HAART versus ZDV/sdNVP during week 3 (3.37 versus 4.02, P = 0.04), as well as over time according to a linear mixed-effects model.
                Cell-free and, to a lesser extent, cell-associated HIV-1 RNA levels in breast milk were suppressed by antiretroviral regimens used to prevent MTCT. However, even with HAART, there was no significant reduction in the reservoir of infected cells, which could contribute to breast milk HIV-1 transmission. To assess hematologic and hepatic toxicities associated with in utero and breastfeeding exposure to maternal highly active antiretroviral therapy (HAART) among infants in Botswana.
                A nested cohort study within a randomized clinical trial (the Mashi Study). Laboratory toxicities among infants born to women who initiated HAART before delivery were compared with toxicities among those born to women who received zidovudine and a single dose of nevirapine or placebo in labor. Infants were randomized to breastfeed with extended zidovudine or to formula-feed.
                Hemoglobin concentrations, absolute neutrophil and platelet counts, and alanine aminotransferase and aspartate aminotransferase levels were recorded from birth to 7 months of age in infants. Grade 3 and 4 toxicities were compared by infant antiretroviral exposure status.
                In-utero exposure to maternal HAART was associated with increased risk for neutropenia in infants up to 1 month of age; 21.7% of HAART-exposed infants were neutropenic, compared with 5.5% of the infants exposed to zidovudine (P < 0.01). However, neutropenia was no longer associated with antenatal exposure to HAART after 1 month of age. Postnatal exposure to HAART was not associated with hematologic or hepatic toxicities. Laboratory toxicities were clinically asymptomatic in all but one infant.
                Exposure to maternal HAART in utero may increase the risk for infant neutropenia, particularly among breastfed infants, but the clinical significance of this finding is uncertain. The lack of association between exposure to HAART through breastfeeding and long-term toxicities in infants is reassuring but deserves study in larger cohorts.
In ART-eligible pregnant women with HIV infection, ART is a safe and effective means of providing maternal virologic suppression, decreasing infant mortality, and reducing MTCT. Specifically, AZT/3TC/NVP, AZT/3TC/LPV-r, and AZT/3TC/ABC have been shown to decrease MTCT. More research is needed regarding the use of specific regimens and their maternal and infant side-effect profiles.