Adapting “MOVE” to accelerate VMMC coverage for HIV prevention in priority populations:Implementation experiences from Uganda’s military settings

This paper describes the WHO’s Model of Optimizing Volumes and Efficiencies (MOVE), adapted by the University Research Council (URC) - Department of Defense HIV/AIDS Prevention Program (DHAPP) to rapidly scale up Voluntary Medical Male Circumcision (VMMC) within Uganda’s military health facilities. First, we examine the MOVE model and then present the URC-DHAPP adapted intervention package comprising of: a) a Command-driven approach, b) Mobile theatres c) Quality assurance d) Data strengthening and reflection. To expand VMMC, URC-DHAPP worked with army commanders to create awareness, mobilize their troops and surgeons were assigned daily targets. The mobile theatre involved regular visits to hard-to-reach outposts and placing several mobile camps at health facilities close to deployment sites. All stakeholders were briefed on performance trends of previous medical camps and the program was monitored through VMMC camp reports. URC-DHAPP registered an exponential increase in VMMC coverage from 13% performance at Q2 to over 140% in Q4. The integrated approach led to circumcision of over 22,000 men (15-49 years) in a record four months. Our approach also contributed to health system strengthening and national HIV preventiontargets. We conclude that the MOVE is cost-effective and can be successfully scaled up in resource-limited settings with a high HIV burden when implemented with cognizance of contextual specificities

Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda

Objectives We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring. Methods NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm3) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL. Phenotypic resistance was expressed as fold-change in IC50 (FC) relative to wild-type virus. Results HIV-1 RNA viral load ≥1000 copies/mL at week 96 was seen in 58/204 (28.4%) cABC participants and 21/159 (13.2%) cNVP participants. Resistance results were available in 35 cABC and 17 cNVP participants; 31 (89%) cABC and 16 (94%) cNVP isolates had a week 96 FC below the biological cut-off for tenofovir (2.2). In the cNVP arm, 16/17 participants had resistance mutations synonymous with high-level resistance to nevirapine and efavirenz; FC values for etravirine were above the biological cut-off in 9 (53%) isolates. In multivariate regression models, K65R, Y115F and the presence of thymidine analogue-associated mutations were associated with increased susceptibility to etravirine in the cABC arm. Conclusions Our data support the use of tenofovir following failure of a first-line zidovudine-containing regimen and shed further light on non-nucleoside reverse transcriptase inhibitor hypersusceptibility

Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Matti A Ristola on SPREAD Programme -työryhmän jäsen.Peer reviewe

Prevalence, incidence and predictors of peripheral neuropathy in African adults with HIV infection within the DART trial

Objectives: We investigated the prevalence, incidence and predictors of new peripheral neuropathy episodes in previously untreated, symptomatic HIV-infected Ugandan/Zimbabwean adults initiating zidovudine-based antiretroviral therapy (ART)

Adapting “MOVE” to Accelerate VMMC Coverage for HIV Prevention in Priority Populations: Implementation Experiences from Uganda’s Military Settings

This paper describes the WHO’s Model of Optimizing Volumes and Efficiencies (MOVE), adapted by the University Research Council (URC) - Department of Defense HIV/AIDS Prevention Program (DHAPP) to rapidly scale up Voluntary Medical Male Circumcision (VMMC) within Uganda’s military health facilities. First, we examine the MOVE model and then present the URC-DHAPP adapted intervention package comprising of: a) a Command-driven approach, b) Mobile theatres c) Quality assurance d) Data strengthening and reflection. To expand VMMC, URC-DHAPP worked with army commanders to create awareness, mobilize their troops and surgeons were assigned daily targets. The mobile theatre involved regular visits to hard-to-reach outposts and placing several mobile camps at health facilities close to deployment sites. All stakeholders were briefed on performance trends of previous medical camps and the program was monitored through VMMC camp reports. URC-DHAPP registered an exponential increase in VMMC coverage from 13% performance at Q2 to over 140% in Q4. The integrated approach led to circumcision of over 22,000 men (15-49 years) in a record four months. Our approach also contributed to health system strengthening and national HIV preventiontargets. We conclude that the MOVE is cost-effective and can be successfully scaled up in resource-limited settings with a high HIV burden when implemented with cognizance of contextual specificities

Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.

BACKGROUND: HIV antiretroviral therapy (ART) is often managed without routine laboratory monitoring in Africa; however, the effect of this approach is unknown. This trial investigated whether routine toxicity and efficacy monitoring of HIV-infected patients receiving ART had an important long-term effect on clinical outcomes in Africa. METHODS: In this open, non-inferiority trial in three centres in Uganda and one in Zimbabwe, 3321 symptomatic, ART-naive, HIV-infected adults with CD4 counts less than 200 cells per microL starting ART were randomly assigned to laboratory and clinical monitoring (LCM; n=1659) or clinically driven monitoring (CDM; n=1662) by a computer-generated list. Haematology, biochemistry, and CD4-cell counts were done every 12 weeks. In the LCM group, results were available to clinicians; in the CDM group, results (apart from CD4-cell count) could be requested if clinically indicated and grade 4 toxicities were available. Participants switched to second-line ART after new or recurrent WHO stage 4 events in both groups, or CD4 count less than 100 cells per microL (LCM only). Co-primary endpoints were new WHO stage 4 HIV events or death, and serious adverse events. Non-inferiority was defined as the upper 95% confidence limit for the hazard ratio (HR) for new WHO stage 4 events or death being no greater than 1.18. Analyses were by intention to treat. This study is registered, number ISRCTN13968779. FINDINGS: Two participants assigned to CDM and three to LCM were excluded from analyses. 5-year survival was 87% (95% CI 85-88) in the CDM group and 90% (88-91) in the LCM group, and 122 (7%) and 112 (7%) participants, respectively, were lost to follow-up over median 4.9 years' follow-up. 459 (28%) participants receiving CDM versus 356 (21%) LCM had a new WHO stage 4 event or died (6.94 [95% CI 6.33-7.60] vs 5.24 [4.72-5.81] per 100 person-years; absolute difference 1.70 per 100 person-years [0.87-2.54]; HR 1.31 [1.14-1.51]; p=0.0001). Differences in disease progression occurred from the third year on ART, whereas higher rates of switch to second-line treatment occurred in LCM from the second year. 283 (17%) participants receiving CDM versus 260 (16%) LCM had a new serious adverse event (HR 1.12 [0.94-1.32]; p=0.19), with anaemia the most common (76 vs 61 cases). INTERPRETATION: ART can be delivered safely without routine laboratory monitoring for toxic effects, but differences in disease progression suggest a role for monitoring of CD4-cell count from the second year of ART to guide the switch to second-line treatment. FUNDING: UK Medical Research Council, the UK Department for International Development, the Rockefeller Foundation, GlaxoSmithKline, Gilead Sciences, Boehringer-Ingelheim, and Abbott Laboratories