Integration of antiretroviral treatment within antenatal care in Gauteng Province, South Africa. Antiretroviral therapy in antenatal care to increase treatment initiation in HIV-infected pregnant women: a stepped-wedge evaluation. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire. A cluster-randomized trial of enhanced labor ward-based PMTCT services to increase nevirapine coverage in Lusaka, Zambia. Results of a community-based antiretroviral treatment program for HIV-1 infection in Western Uganda. A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers. Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa.
Antenatal clinics are a key entry point into HIV treatment and care, together with interventions to reduce mother-to-child transmission (MTCT). Further evaluation is needed of interventions linking antenatal with antiretroviral (ARV) treatment services and effectiveness of triple-ARV regimens for reducing MTCT in resource-constrained settings.
                Data were gathered from HIV-infected women attending antenatal care from June 2004 to July 2005 at Coronation Women and Children Hospital, South Africa. After a patient record review, interventions were implemented to strengthen service linkages and integrate ARV treatment within antenatal care. Laboratory investigations were streamlined, including CD4 cell count testing at the first antenatal visit. MTCT risk for women initiating ARV treatment is compared with that of women-infant pairs receiving single-dose nevirapine (sd-NVP).
                In total, 164 pregnant women initiated ARV treatment and 863 received sd-NVP. After changes to service delivery, time-to-treatment initiation was reduced from a median of 56 days to 37 days (P = 0.041). The risk of MTCT for women receiving ARV treatment (5 [4.3%] of 116 women) was lower than for those given sd-NVP (74 [10.7%] of 692 women; P = 0.032).
                Strengthening linkages and integrating key components of ARV treatment within antenatal care reduces time-to-treatment initiation. In this setting, among women with a high MTCT risk, triple-ARV regimens are effective in reducing HIV infection in infants. The objective of the study was to evaluate whether providing antiretroviral therapy (ART) integrated in antenatal care (ANC) clinics resulted in a greater proportion of treatment-eligible women initiating ART during pregnancy compared with the existing approach of referral to ART. ANALYSIS DESIGN AND METHODS: The evaluation used a stepped-wedge design and included all HIV-infected, ART-eligible pregnant women in eight public sector clinics in Lusaka district, Zambia. Main outcome indicators were the proportion of treatment-eligible pregnant women enrolling into HIV care within 60 days of HIV diagnosis, and of these, the proportion initiating ART during pregnancy. Adjusted odds ratios (AORs) and confidence intervals (CIs) for enrollment and initiation proportions were estimated through a logistic regression model accounting for clinical site cluster and time effects.
                Between 16 July 2007 and 31 July 2008, 13,917 women started antenatal care more than 60 days before the intervention rollout and constituted the control cohort; 17 619 started antenatal care after ART integrated into ANC and constituted the intervention cohort. Of the 1566 patients found eligible for ART, a greater proportion enrolled while pregnant and within the 60 days of HIV diagnosis in the intervention cohort (376/846, 44.4%) compared with the control cohort (181/716, 25.3%), AOR 2.06, 95% CI (1.27-3.34); and initiated ART while pregnant in the intervention cohort (278/846, 32.9%) compared with the control cohort (103/716, 14.4%), AOR 2.01, 95% CI (1.37-2.95).
                An integrated ART in ANC strategy doubled the proportion of treatment-eligible women initiating ART while pregnant. To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6) for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups, respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%) and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries. Infants infected with HIV-1 perinatally despite single-dose nevirapine progress rapidly. Data on treatment outcome in sub-Saharan African infants exposed to single-dose nevirapine are urgently required. This feasibility study addresses efficacy of infant antiretroviral therapy in this setting.
                HIV-infected infants in Durban, South Africa, received randomized immediate or deferred (when CD4 cell count reached <20%) four-drug antiretroviral therapy (zidovudine/lamivudine/nelfinavir/nevirapine). Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken pre-antiretroviral therapy. Monthly follow-up to 1-year post-antiretroviral therapy included viral load, CD4 cell count and verbal/measured adherence monitoring.
                All 63 infants were exposed to single-dose nevirapine. Twenty-one out of 51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Forty-three infants were randomized to immediate antiretroviral therapy (ART): three withdrew pre-antiretroviral therapy; 36 out of 40 completed 1-year of ART. Twenty infants received deferred ART: 17 reached CD4 cell counts less than 20% (median d99) and 13 out of 17 started antiretroviral therapy in year 1. Verbal and measured adherence was 99% and 95%, respectively. One-year post-ART, 49 out of 49 (100%) infants had a viral load less than 400 copies/ml; 46 out of 49 (94%) had viral load less than 50 copies/ml. Ten infants (20%) required second-line ART due to virological failure or tuberculosis treatment, therefore 39 out of 49 (80%) achieved viral load less than 400 copies/ml by intention-to-treat. Time to viral load less than 50 copies/ml correlated with maternal CD4 cell count (r = -0.42; P = 0.005) and infant pre-ART viral load (r = 0.64; P < 0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.
                Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression. Infants remain relatively neglected in roll-out programmes and ART provision must be expanded. 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. Determine whether enhanced labor ward-based services for prevention of mother-to-child transmission of HIV (PMTCT) would improve nevirapine (NVP) coverage.
                Cluster-randomized trial at 12 public-sector delivery centers in Lusaka, Zambia.
                Following a baseline surveillance period, 12 labor wards were randomized, six to offer opt-in HIV testing to women of unknown serostatus (with NVP administration as indicated) and to assess NVP adherence among known HIV-infected women. The six control labor wards provided the standard of care. The NVP coverage endpoint was defined as the proportion of HIV-infected/exposed women/infant pairs with confirmed NVP ingestion. We used generalized estimating equations (GEE) to determine the odds of coverage associated with the intervention and ultimately used the parameters for the estimated GEE model to estimate relative risk.
                Between October 2005 and January 2006, 7664 women gave birth at participating clinics. We collected anonymous-linked blood from 7592 (99%) umbilical cords; tested 7438 (97%) for HIV, 1618 (22%) were seropositive, and of these, 1279 (79%) were tested for NVP. At baseline (preintervention), the probability of HIV-infected/exposed women/infant pairs receiving NVP in treatment clinics (42%) was 0.89 times the probability of being covered in control clinics (53%) whereas during the intervention period the probability of treatment clinic coverage (52%) was 1.22 the probability control clinic coverage (43%), representing a multiplicative effect of 1.37 upon the RR at baseline (ratio of relative risks 1.37, bootstrapped 95% CI, 1.04-1.77).
                Labor ward-based PMTCT programs are feasible and can have a significant, positive impact on NVP coverage. To compare the treatment outcomes and mortality in a rural community-based ART (CBART) program with a hospital-based ART program in the same district.
                The study design was a non-randomized cohort study consisting of 185 persons living with HIV (PLWHIV) in the CBART cohort and 200 PLWHIV in the hospital cohort. Eligibility for both cohorts was: being HIV-infected and eligible for ART, being treatment naïve, age 18 years or older, and being a resident of Rwimi sub-county. The intervention consisted of a community-based program which included weekly home visits to patients by trained volunteers who delivered antiretroviral drugs (ARVs), monitored and supported adherence to treatment, and identified and reported adverse reactions and other clinical symptoms. Outcome variables were compared to patients in a hospital-based cohort who received the standard care delivered to all other HIV patients in the hospital. The main outcome measures were HIV-1 RNA viral load (VL), CD4 cell count and mortality after six months of treatment.
                Successful ART treatment outcome as measured by virological suppression (VL<400 copies/ml) in the CBART cohort were similar to those in the hospital-based cohort (90.1% vs 89.3%, p=0.47). The median CD4 cell count increased significantly in both cohorts (community-based cohort 159 cells/microl vs 145 cells/microl in the hospital-based cohort). Mortality was not significantly different in both cohorts (community-based cohort 11.9%, hospital-based cohort 9.0%).
                The findings show that outcomes of a CBART intervention in a rural area compare favorably to outcomes of hospital-based care. If the study results are sustainable over a longer time period, this model could be considered for ART roll-out to impoverished rural/remote populations in Uganda and elsewhere. Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy.
                This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis.
                Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006).
                A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection. BACKGROUND. Cryptococcal meningitis (CM) remains a leading cause of acquired immunodeficiency syndrome-related death in sub-Saharan Africa. The timing of the initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV)-associated CM remains uncertain. The study aimed to determine the optimal timing for initiation of ART in HIV-positive individuals with CM. METHODS. A prospective, open-label, randomized clinical trial was conducted at a tertiary teaching hospital in Zimbabwe. Participants were aged > or = 18 years, were ART naive, had received a first CM diagnosis, and were randomized to receive early ART (within 72 h after CM diagnosis) or delayed ART (after 10 weeks of treatment with fluconazole alone). Participants received 800 mg of fluconazole per day. The ART regimen used was stavudine, lamivudine, and nevirapine given twice daily. The duration of follow-up was up to 3 years. The primary end point was all-cause mortality. RESULTS. Fifty-four participants were enrolled in the study (28 in the early ART arm and 26 in the delayed ART arm). The median CD4 cell count at enrollment was 37 cells/mm(3) (interquartile range, 17-69 cells/mm(3)). The 3-year mortality rate differed significantly between the early and delayed ART groups (88% vs 54%; P < .006); the overall 3-year mortality rate was 73%. The median durations of survival were 28 days and 637 days in the early and delayed ART groups, respectively (P = .031, by log-rank test). The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group (adjusted hazard ratio, 2.85; 95% confidence interval, 1.1-7.23). The study was terminated early by the data safety monitoring committee. CONCLUSIONS. In resource-limited settings where CM management may be suboptimal, when compared with a delay of 10 weeks after a CM diagnosis, early initiation of ART results in increased mortality. Trial registration. ClinicalTrials.gov identifier: NCT00830856.
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.