Search

Background: With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa., Methods: Pooled analysis of routine individual data from children who initiated ART in 7 South African treatment programs with 6-monthly viral load and CD4 monitoring produced Kaplan-Meier estimates of probability of virologic failure (2 consecutive unsuppressed viral loads with the second being >1000 copies/mL, after ≥24 weeks of therapy) and switch to second-line. Cox-proportional hazards models stratified by program were used to determine predictors of these outcomes., Results: The 3-year probability of virologic failure among 5485 children was 19.3% (95% confidence interval: 17.6 to 21.1). Use of nevirapine or ritonavir alone in the initial regimen (compared with efavirenz) and exposure to prevention of mother to child transmission regimens were independently associated with failure [adjusted hazard ratios (95% confidence interval): 1.77 (1.11 to 2.83), 2.39 (1.57 to 3.64) and 1.40 (1.02 to 1.92), respectively]. Among 252 children with ≥1 year follow-up after failure, 38% were switched to second-line. Median (interquartile range) months between failure and switch was 5.7 (2.9-11.0)., Conclusions: Triple ART based on nevirapine or ritonavir as a single protease inhibitor seems to be associated with a higher risk of virologic failure. A low proportion of virologically failing children were switched.

Background: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account., Patients and Methods: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year., Results: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV)., Conclusions: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.

Background: Limited information exists about effects of different highly active antiretroviral therapy (HAART) regimens and duration of regimens on mother-to-child transmission (MTCT) of HIV among women in Africa who start treatment for advanced immunosuppression., Methods: Between January 2004 to August 2008, 1142 women were followed at antenatal antiretroviral clinics in Johannesburg. Predictors of MTCT (positive infant HIV DNA polymerase chain reaction at 4-6 weeks) were assessed with multivariate logistic regression., Results: Mean age was 30.2 years (SD = 5.0) and median baseline CD4 count was 161 cells per cubic millimeter (SD = 84.3). HAART duration at time of delivery was a mean 10.7 weeks (SD = 7.4) for the 85% of women who initiated treatment during pregnancy and 93.4 weeks (SD = 37.7) for those who became pregnant on HAART. Overall MTCT rate was 4.9% (43 of 874), with no differences detected between HAART regimens. MTCT rates were lower in women who became pregnant on HAART than those initiating HAART during pregnancy (0.7% versus 5.7%; P = 0.01). In the latter group, each additional week of treatment reduced odds of transmission by 8% (95% confidence interval: 0.87 to 0.99, P = 0.02)., Conclusions: Late initiation of HAART is associated with increased risk of MTCT. Strategies are needed to facilitate earlier identification of HIV-infected women.

Background: 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., Methods: 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)., Results: 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)., Conclusions: 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.