Introducing a multi-site program for early diagnosis of HIV infection among HIV-exposed infants in Tanzania

<p>Abstract</p> <p>Background</p> <p>In Tanzania, less than a third of HIV infected children estimated to be in need of antiretroviral therapy (ART) are receiving it. In this setting where other infections and malnutrition mimic signs and symptoms of AIDS, early diagnosis of HIV among HIV-exposed infants without specialized virologic testing can be a complex process. We aimed to introduce an Early Infant Diagnosis (EID) pilot program using HIV DNA Polymerase Chain Reaction (PCR) testing with the intent of making EID nationally available based on lessons learned in the first 6 months of implementation.</p> <p>Methods</p> <p>In September 2006, a molecular biology laboratory at Bugando Medical Center was established in order to perform HIV DNA PCR testing using Dried Blood Spots (DBS). Ninety- six health workers from 4 health facilities were trained in the identification and care of HIV-exposed infants, HIV testing algorithms and collection of DBS samples. Paper-based tracking systems for monitoring the program that fed into a simple electronic database were introduced at the sites and in the laboratory. Time from birth to first HIV DNA PCR testing and to receipt of test results were assessed using Kaplan-Meier curves.</p> <p>Results</p> <p>From October 2006 to March 2007, 510 HIV-exposed infants were identified from the 4 health facilities. Of these, 441(87%) infants had an HIV DNA PCR test at a median age of 4 months (IQR 1 to 8 months) and 75(17%) were PCR positive. Parents/guardians for a total of 242(55%) HIV-exposed infants returned to receive PCR test results, including 51/75 (68%) of those PCR positive, 187/361 (52%) of the PCR negative, and 4/5 (80%) of those with indeterminate PCR results. The median time between blood draw for PCR testing and receipt of test results by the parent or guardian was 5 weeks (range <1 week to 14 weeks) among children who tested PCR positive and 10 weeks (range <1 week to 21 weeks) for those that tested PCR negative.</p> <p>Conclusions</p> <p>The EID pilot program successfully introduced systems for identification of HIV-exposed infants. There was a high response as hundreds of HIV-exposed infants were registered and tested in a 6 month period. Challenges included the large proportion of parents not returning for PCR test results. Experience from the pilot phase has informed the national roll-out of the EID program currently underway in Tanzania.</p

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