Although simple and low-cost interventions for sickle cell disease (SCD) exist in many developing countries, child mortality associated with SCD remains high, in part, because of the lack of access to diagnostic tests for SCD. A density-based test using aqueous multiphase systems (SCD-AMPS) is a candidate for a low-cost, point-of-care diagnostic for SCD. In this paper, the field evaluation of SCD-AMPS in a large (n = 505) case-control study in Zambia is described. Of the two variations of the SCD-AMPS used, the best system (SCD-AMPS-2) demonstrated a sensitivity of 86% (82–90%) and a specificity of 60% (53–67%). Subsequent analysis identified potential sources of false positives that include clotting, variation between batches of SCD-AMPS, and shipping conditions. Importantly, SCD-AMPS-2 was 84% (62–94%) sensitive in detecting SCD in children between 6 months and 1 year old. In addition to an evaluation of performance, an assessment of end-user operability was done with health workers in rural clinics in Zambia. These health workers rated the SCD-AMPS tests to be as simple to use as lateral flow tests for malaria and HIV.

Background. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) P1060 study demonstrated short-term superiority of lopinavir/ritonavir (LPV/r) over nevirapine (NVP) in antiretroviral therapy (ART), regardless of prior NVP exposure. However, NVP-based ART had a marginal benefit in CD4 percentage (CD4%) and growth. We compared 5-year outcomes from this clinical trial.Methods. Human immunodeficiency virus (HIV)-infected, ART-eligible children were enrolled into 2 cohorts based on prior NVP exposure and randomized to NVP-or LPV/r-based ART. The data safety monitoring board recommended unblinding results in both cohorts due to superiority of LPV/r for the primary endpoint: stopping randomized treatment, virologic failure (VF), or death by 6 months. Participants were offered a switch in regimens (if on NVP) and continued observational follow-up. We compared time to VF or death, death, and CD4% and growth changes using intention-to-treat analyses. Additionally, inverse probability weights were used to account for treatment switching and censoring.Results. As of September 2014, 329 of the 451 (73%) enrolled participants were still in follow-up (median, 5.3 years; interquartile range [IQR], 4.3-6.4), with 52% on NVP and 88% on LPV/r as originally randomized. NVP arm participants had significantly higher risk of VF or death (adjusted hazard ratio [aHR], 1.90; 95% confidence interval [CI], 1.37-2.65) but not death alone (aHR, 1.65; 95% CI, .72-3.76) compared with participants randomized to LPV/r. Mean CD4% was significantly higher in the NVP arm up to 1 year after ART initiation, but not beyond. Mean weight-for-age z scores were marginally higher in the NVP arm, but height-for-age z scores did not differ. Similar trends were observed in sensitivity analyses.Conclusions. These findings support the current World Health Organization recommendation of LPV/r in first-line ART regimens for HIV-infected children.Clinical Trials Registration. NCT00307151.

Objectives To describe the pattern of incident illness in children after initiation of antiretroviral therapy (ART) in a large public health sector in Lusaka, Zambia. Methods A systematic review was performed to extract data from medical records of children (i.e., under 16 years) initiating ART in the Lusaka, Zambia HIV care and treatment program. Incident conditions were listed separately and then grouped according to broad categories. Predictors for incident diagnoses were determined using univariate and multivariable analysis. Results Between May 2004 and July 2006, 1,940 HIV-infected children initiated ART. Of these, 1,391 (71.1%) had their medical records reviewed. Median age at ART initiation was 77 months and 631 (45.4%) were females. 859 (62%) children had an incident condition during this period, with a median time of occurrence of 63 days from ART initiation. 28 different incident conditions were documented. When categorized, the most common were mucocutaneous conditions (incidence rate [IR]: 101.1 per 100 child-years, 95%CI: 92.3-110.5) and upper respiratory tract infection (IR: 100.6 per 100 child-years; 95% CI 91.9-110.0). Children with severe immunosuppression (i.e., CD4 < 10%) were more likely to develop lower respiratory tract infection (15.4% vs. 8.4%; p = 0.0002), mucocutaneous conditions (41.3% vs. 29.5%; p < 0.0001) and gastrointestinal conditions (19.8% vs. 14.5%; p = 0.02), when compared to those with CD4 ≥ 10%. Conclusion There is a high incidence of new illness following ART initiation, emphasizing the importance of close monitoring during this period.

Background In a randomized trial comparing nevirapine (NVP)- versus lopinavir/ritonavir (LPV/r)– based antiretroviral therapy (ART) in HIV-infected children (primary endpoint discontinuation of study treatment for any reason or virologic failure (VF) by week 24) aged two months to three years, we assessed whether clinical, virologic, immunologic and safety outcomes varied by prior single-dose NVP exposure (PrNVP) for prevention of mother-to-child HIV transmission and other covariates. Methods Efficacy was assessed by time to ART discontinuation or VF, VF/death, and death; safety by time to ART discontinuation due to a protocol-defined toxicity and first ≥ grade 3 adverse event; immunology and growth by changes in CD4%, weight/height WHO z-scores from entry to week 48. Cox proportional hazards and linear regression models were used to test whether treatment differences depended on PrNVP exposure and other covariates. Results Over a median follow-up of 48 (PrNVP) and 72 (No PrNVP) weeks, there was no evidence of differential treatment effects by PrNVP exposure or any other covariates. LPV/r – based ART was superior to NVP-based ART for efficacy and safety outcomes but those on NVP had larger improvements in CD4%, weight and height z-scores. Lower pre-treatment CD4% and higher HIV-1 RNA levels were associated with reduced efficacy, lower pre-treatment CD4% with shorter time to ART discontinuation due to a protocol-defined toxicity, and no PrNVP with shorter time to first grade ≥3 adverse event. Conclusions Differences between LPV/r and NVP ART in efficacy, safety, immunologic and growth outcomes did not depend on PrNVP exposure, prior breastfeeding, sex, HIV-1 subtype, age, pre-treatment CD4%, HIV-1 RNA or WHO disease stage. This finding should be considered when selecting an ART regimen for young children.

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