Tuberculosis in Pediatric Antiretroviral Therapy Programs in Low- and Middle-Income Countries: Diagnosis and Screening Practices

Background The global burden of childhood tuberculosis (TB) is estimated to be 0.5 million new cases per year. Human immunodeficiency virus (HIV)-infected children are at high risk for TB. Diagnosis of TB in HIV-infected children remains a major challenge. Methods We describe TB diagnosis and screening practices of pediatric antiretroviral treatment (ART) programs in Africa, Asia, the Caribbean, and Central and South America. We used web-based questionnaires to collect data on ART programs and patients seen from March to July 2012. Forty-three ART programs treating children in 23 countries participated in the study. Results Sputum microscopy and chest Radiograph were available at all programs, mycobacterial culture in 40 (93%) sites, gastric aspiration in 27 (63%), induced sputum in 23 (54%), and Xpert MTB/RIF in 16 (37%) sites. Screening practices to exclude active TB before starting ART included contact history in 41 sites (84%), symptom screening in 38 (88%), and chest Radiograph in 34 sites (79%). The use of diagnostic tools was examined among 146 children diagnosed with TB during the study period. Chest Radiograph was used in 125 (86%) children, sputum microscopy in 76 (52%), induced sputum microscopy in 38 (26%), gastric aspirate microscopy in 35 (24%), culture in 25 (17%), and Xpert MTB/RIF in 11 (8%) children. Conclusions Induced sputum and Xpert MTB/RIF were infrequently available to diagnose childhood TB, and screening was largely based on symptom identification. There is an urgent need to improve the capacity of ART programs in low- and middle-income countries to exclude and diagnose TB in HIV-infected childre

Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1

International audienceBACKGROUND: An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings.METHODS: We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points.RESULTS: A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%).CONCLUSIONS: In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.)

Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa.

International audienceWhile dolutegravir has been added by WHO as a preferred second-line option for the treatment of HIV infection, boosted protease inhibitor (bPI)-based regimens are still needed as alternative second-line options. Identifying optimal bPI-based second-line combinations is essential, given associated high costs and funding constraints in low- and middle-income countries. We assessed the cost-effectiveness of three alternative bPI-based second-line regimens in Burkina Faso, Cameroon and Senegal.METHODS: We used data collected over 2010-2015 in the 2LADY trial/post-trial cohort. Patients with first-line antiretroviral therapy (ART) failure were randomly assigned to tenofovir/emtricitabine + lopinavir/ritonavir (TDF/FTC LPV/r; arm A), abacavir + didanosine + lopinavir/ritonavir (arm B), or tenofovir/emtricitabine + darunavir/ritonavir (arm C). Costs (US dollars, 2016), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were computed for each country over 24 months of follow-up and extrapolated to 5 years using a simulated patient-level Markov model. We assessed uncertainty using cost-effectiveness acceptability curves, scenarios and prices threshold analysis.RESULTS: In each country, over 24 months, arm A was significantly less costly than arms B and C (incremental costs ranging from US$410-$US721 and US$468-US$546 for B and C vs A, respectively) and offered similar health benefits (incremental QALY: - 0.138 to 0.023 and - 0.179 to 0.028, respectively). Over 5 years, arm A remained the least costly, health benefits not being significantly different between arms. Compared with arms B and C, in each study country, Arm A had a ≥ 95% probability of being cost-effective for a large range of cost-effectiveness thresholds, irrespective of the scenario considered.CONCLUSIONS: Using TDF/FTC LPV/r as a bPI-based second-line regimen provided the best economic value in the three study countries