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The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR's implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR's contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.

Background: Uganda aims to provide safe male circumcision (SMC) to 80% of men ages 15-49 by 2016. To date, only 2 million men have received SMC of the 4.2 million men required. In response to age and regional trends in SMC uptake, the country sought to re-examine its targets with respect to age and subnational region, to assess the program's progress, and to refine the implementation approach., Methods and Findings: The Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0), was used in conjunction with incidence projections from the Spectrum/AIDS Impact Module (AIM) to conduct this analysis. Population, births, deaths, and HIV incidence and prevalence were used to populate the model. Baseline male circumcision prevalence was derived from the 2011 AIDS Indicator Survey. Uganda can achieve the most immediate impact on HIV incidence by circumcising men ages 20-34. This group will also require the fewest circumcisions for each HIV infection averted. Focusing on men ages 10-19 will offer the greatest impact over a 15-year period, while focusing on men ages 15-34 offers the most cost-effective strategy over the same period. A regional analysis showed little variation in cost-effectiveness of scaling up SMC across eight regions. Scale-up is cost-saving in all regions. There is geographic variability in program progress, highlighting two regions with low baseline rates of circumcision where additional efforts will be needed., Conclusion: Focusing SMC efforts on specific age groups and regions may help to accelerate Uganda's SMC program progress. Policy makers in Uganda have already used model outputs in planning efforts, proposing males ages 10-34 as a priority group for SMC in the 2014 application to the Global Fund's new funding model. As scale-up continues, the country should also consider a greater effort to expand SMC in regions with low MC prevalence.

Background: The Ugandan Ministry of Health has endorsed voluntary medical male circumcision as an HIV prevention strategy and has set ambitious goals (e.g., 4.2 million circumcisions by 2015). Innovative strategies to improve access for hard to reach, high risk, and poor populations are essential for reaching such goals. In 2009, the Makerere University Walter Reed Project began the first facility-based VMMC program in Uganda in a non-research setting. In addition, a mobile clinic began providing VMMC services to more remote, rural locations in 2011. The primary objective of this study was to estimate the average cost of performing VMMCs in the mobile clinic compared to those performed in health facilities (fixed sites). The difference between such costs is the cost of improving access to VMMC., Methods: A micro-costing approach was used to estimate costs from the service provider's perspective of a circumcision. Supply chain and higher-level program support costs are not included., Results: The average cost (US$2012) of resources used per circumcision was $61 in the mobile program ($72 for more remote locations) compared to $34 at the fixed site. Costs for community mobilization, HIV testing, the initial medical exam, and staff for performing VMMC operations were similar for both programs. The cost of disposable surgical kits, the additional upfront cost for the mobile clinic, and additional costs for staff drive the differences in costs between the two programs. Cost estimates are relatively insensitive to patient flow over time., Conclusion: The MUWRP VMMC program improves access for hard to reach, relatively poor, and high-risk rural populations for a cost of $27-$38 per VMMC. Costs to patients to access services are almost certainly less in the mobile program, by reducing out-of-pocket travel expenses and lost time and associated income, all of which have been shown to be barriers for accessing treatment.

HIV-1 viral load (VL) monitoring is recommended but seldom performed in resource-constrained countries. An evaluation of patients receiving first-line antiretroviral therapy in a multicountry PEPFAR program (RV288) was performed to determine the rates and predictors of virologic suppression. Resistance data from treatment failures are available from Uganda and Nigeria. Each country enrolled 325 subjects into this cross-sectional study. Subjects on first-line therapy were randomly selected for HIV RNA testing (viral load). Regimens included efavirenz or nevirapine with zidovudine/lamivudine or tenofovir/lamivudine. VL was determined from plasma using the Roche COBAS TaqMan HIV-1 Test, High Pure System v1.0 (47 copies/ml). Genotypic resistance testing was performed on samples with VL>1,000 copies/ml. From Uganda, 85% of subjects were undetectable while 7% (23/325) had VL>1,000 copies/ml. The HIV-1 subtype distribution was as follows: A=47.6%, C=14.3%, and D=38.1%. No resistance mutations were found in 14% of subjects. All subjects with resistance had the M184V mutation. Of subjects failing a zidovudine regimen less than 1 year, 88% (7/8) had no thymidine analogue mutations (TAMs), compared to 50% (4/8) failing greater than 1 year. Four subjects (25%) had more than two mutations from the TAM-1 pathway (41L, 210W, 215Y). In Nigeria, 82% were undetectable while 14% (45/325) had VL>1,000 copies/ml. HIV-1 subtype distribution was as follows: 62.8%=CRF02_AG, 34%=pure G, and 2.8%=A. Of the 35 genotyped subjects, 14% (5/35) had no resistance mutations. Of the remainder, 10% (3/30) had no nucleoside analogue mutations while 33% (10/30) had only M184V along with nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations. Forty percent (10/25) of subjects on zidovudine failed without TAMs. Another 25% (5/25) of subjects failing on zidovudine had more than two TAM-1 mutations. Individuals failing first-line antiretroviral therapy (ART) may retain sensitivity to one or more nucleoside analogues from the regimen. Knowledge of drug resistance patterns allow for selection of drugs that can be recycled in future regimens. Accumulation of resistance mutations may compromise future treatment options.