An Efficient, Large-Scale Survey of Hepatitis C Viremia in the Democratic Republic of the Congo Using Dried Blood Spots

Background Efficient viral load testing is needed for hepatitis C (HCV) surveillance and diagnosis. HCV viral load testing using dried blood spots (DBSs), made with a single drop of finger-prick whole blood on filter paper, is a promising alternative to traditional serum-or plasma-based approaches. Methods We adapted the Abbott Molecular m2000 instrument for high-Throughput HCV viremia testing using DBSs with simple specimen processing and applied these methods to estimate the national burden of infection in the Democratic Republic of the Congo (DRC). We tested DBSs collected during the 2013-2014 DRC Demographic and Health Survey, including 1309 adults ≥40 years of age. HCV-positive samples underwent targeted sequencing, genotyping, and phylogenetic analyses. Results This high-Throughput screening approach reliably identified HCV RNA extracted from DBSs prepared using whole blood, with a 95% limit of detection of 1196 (95% confidence interval [CI], 866-2280) IU/mL for individual 6-mm punches and 494 (95% CI, 372-1228) IU/mL for larger 12-mm punches. Fifteen infections were identified among samples from the DRC Demographic and Health Surveythe weighted country-wide prevalence of HCV viremia was 0.9% (95% CI, 0.3%-1.6%) among adults ≥40 years of age and 0.7% (95% CI,.6%-.8%) among human immunodeficiency virus-infected subjects. All successfully genotyped cases were due to genotype 4 infection. Conclusions DBS-based HCV testing represents a useful tool for the diagnosis and surveillance of HCV viremia and can easily be incorporated into specimen referral systems. Among adults ≥40 years of age in the DRC, 100000-200000 may have active infection and be eligible for treatment

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated