The transient effect of a peer support intervention to improve adherence among adolescents and young adults failing antiretroviral therapy in Harare, Zimbabwe: a randomized control trial.

BACKGROUND: Adolescents and young adults living with HIV in sub Saharan Africa are at high risk of poor adherence to antiretroviral therapy (ART) and virologic failure (VF). METHODS: We conducted a randomized control trial among adolescents and young adults on ART with VF to assess the effectiveness of a community-based peer support intervention aimed at improving VF. Viral load (VL) levels were obtained at 12, 24 and 36 weeks. A subset of the participants had baseline HIV drug resistance (HIVDR) genotyped using Sanger sequencing. RESULTS: The participants' median (interquartile range (IQR)) age was 18.1 (IQR: 15.1-20.0) years and half (50.5%, n = 107) were male. At week 24, the proportion of subjects with a detectable viremia was significantly lower in the intervention arm than in the standard of care (SOC) arm (76.0% (n = 79) vs. 89.0% (n = 96), p = 0.013). At Week 36, there remained a difference in the proportion of subjects with a detectable VL between the intervention arm (68.3%, n = 71) and SOC arm (79.6%, n = 86), which was trending towards statistical significance (p = 0.059). There was no difference in the probability of having a detectable VL over time between the intervention and SOC groups (adjusted odds ratio: 1.14, p = 0.439). Baseline HIVDR was observed in 44.0% of the participants in the intervention and 56.0% in the SOC group (p = 0.146). CONCLUSION: A transient effect of the peer support intervention in improving VF was observed among adolescents and young people failing ART. TRIAL REGISTRATION: This study is registered with www.clinicaltrials.gov under the reference number: NCT02833441.

A Simple Phosphate-Buffered-Saline-Based Extraction Method Improves Specificity of HIV Viral Load Monitoring Using Dried Blood Spots.

Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (<20 copies/ml in plasma or <400 copies/ml in DBS), and VL of <1,000 copies/ml, and VL of <5,000 copies/ml. Reported plasma VL ranged from TND, or <20, to 5,781,592 copies/ml, and DBS VL ranged from TND, or <400, to 467,600 copies/ml. At <1000 copies/ml, agreement between DBS and plasma was 96.7% (kappa coefficient, 0.93; P < 0.0001). The mean difference between DBS and plasma VL values was -1.06 log10 copies/ml (95% confidence interval [CI], -1.17, -0.97; P < 0.0001). At a treatment failure threshold of >1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system.

Temporal Improvements in Long-term Outcome in Care Among HIV-infected Children Enrolled in Public Antiretroviral Treatment Care: An Analysis of Outcomes From 2004 to 2012 in Zimbabwe.

BACKGROUND: Increasing numbers of children are requiring long-term HIV care and antiretroviral treatment (ART) in public ART programs in Africa, but temporal trends and long-term outcomes in care remain poorly understood. METHODS: We analyzed outcomes in a longitudinal cohort of infants (<2 years of age) and children (2-10 years of age) enrolling in a public tertiary ART center in Zimbabwe over an 8-year period (2004-2012). RESULTS: The clinic enrolled 1644 infants and children; the median age at enrollment was 39 months (interquartile range: 14-79), with a median CD4% of 17.0 (interquartile range: 11-24) in infants and 15.0 (9%-23%) in children (P = 0.0007). Among those linked to care, 33.5% dropped out of care within the first 3 months of enrollment. After implementation of revised guidelines in 2009, decentralization of care and increased access to prevention of mother to child transmission services, we observed an increase in infants (48.9%-68.3%; P < 0.0001) and children (48.9%-68.3%; P < 0.0001) remaining in care for more than 3 months. Children enrolled from 2009 were younger, had lower World Health Organization clinical stage, improved baseline CD4 counts than those who enrolled in 2004-2008. Long-term retention in care also improved with decreasing risk of loss from care at 36 months for infants enrolled from 2009 (aHR: 0.57; 95% confidence interval: 0.34-0.95; P = 0.031). ART eligibility at enrollment was a significant predictor of long-term retention in care, while delayed ART initiation after 5 years of age resulted in failure to fully reconstitute CD4 counts to age-appropriate levels despite prolonged ART. CONCLUSIONS: Significant improvements have been made in engaging and retaining children in care in public ART programs in Zimbabwe. Guideline and policy changes that increase access and eligibility will likely to continue to support improvement in pediatric HIV outcomes.