Douglas Black

A CMV DNA vaccine primes for memory immune responses to live-attenuated CMV (Towne strain).

CMV-seronegative subjects vaccinated intramuscularly or intradermally with a DNA vaccine encoding pp65, IE1, and gB were administered live-attenuated CMV (Towne) to characterize immune priming by the DNA vaccine. CMV-specific memory T-cells (detected by standard ELISPOT assay in only 20% of subjects) were detected by IFN-gamma cultured ELISPOT assay in 60% of subjects primed intramuscularly and correlated with immune responses after Towne. The median time to first pp65 T-cell and gB antibody response after Towne was 14 days for DNA-primed subjects vs. 28 days for controls administered Towne only (p=0.02 and 0.03, respectively). Furthermore, there was a trend toward more DNA-vaccinated subjects than controls developing a gB-specific IFN-gamma T-cell response after Towne administration (47% vs. 0%, p=0.06).

Assessment of Population-Based HIV RNA Levels in a Rural East African Setting Using a Fingerprick-Based Blood Collection Method

BACKGROUND Population-based human immunodeficiency virus type 1 (HIV-1) RNA levels (viral load [VL]) are proposed metrics for antiretroviral therapy (ART) program effectiveness. We estimated population-based HIV RNA levels using a fingerprick-based approach in a rural Ugandan community implementing rapid ART scale-up. METHODS A fingerprick-based HIV RNA measurement technique was validated against standard phlebotomy. This technique was deployed during a 5-day community-wide health campaign in a 6300-person community. Assessments included rapid HIV antibody testing, VL, and CD4+ T-cell count via fingerprick. We estimated population HIV RNA levels and the prevalence of undetectable RNA, assessed predictors of VL via linear regression, and mapped RNA levels within community geographic units. RESULTS During the community-wide health campaign, 179 of 2282 adults (7.8%) and 10 of 1826 children (0.5%) tested seropositive for HIV. Fingerprick VL was determined in 174 of 189 HIV-positive persons (92%). The mean log(VL) was 3.67 log (95% confidence interval [CI], 3.50-3.83 log copies/mL), median VL was 2720 copies/mL (interquartile range, <486-38 120 copies/mL), and arithmetic mean VL was 64 064 copies/mL. Overall, 64 of 174 of individuals had undetectable RNA (37% [95% CI, 30%-44%]), 24% had VL 486-10 000; 25% had VL 10 001-100 000; and 15% had VL>100 000 copies/mL. Among participants taking ART, 83% had undetectable VL. CONCLUSIONS We developed and implemented a fingerprick VL testing method and provide the first report of population HIV RNA levels in Africa. In a rural Ugandan community experiencing ART scale-up, we found evidence of population-level ART effectiveness, but found a substantial population to be viremic, in need of ART, and at risk for transmission.

Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa

Importance Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression. Objective To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa. Design, Setting, and Participants Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV. Main Outcomes and Measures Primary outcome was viral suppression (plasma HIV RNA<500 copies/mL) among all HIV-positive individuals, assessed at baseline and after 1 and 2 years. Secondary outcomes included HIV diagnosis, ART among previously diagnosed individuals, and viral suppression among those who had initiated ART. Results Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Conclusions and Relevance Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation. Trial Registration clinicaltrials.gov Identifier: NCT01864683

Evaluating linkage to care for hypertension after community-based screening in rural Uganda

To determine the frequency and predictors of hypertension linkage to care after implementation of a linkage intervention in rural Uganda.

Changes in Population HIV RNA Levels in Mbarara, Uganda, During Scale-up of HIV Antiretroviral Therapy Access:

Objective:In a rural Ugandan community scaling up antiretroviral therapy (ART), we sought to determine if population-based HIV RNA levels [population viral load (VL)] decreased from 2011 to 2012. Design:Serial cross-sectional analyses (May 2011 and May 2012) of a defined study community of 6300 persons in a district with HIV prevalence of 8%. Methods:We measured HIV-1 RNA (VL) levels on all individuals testing positive for HIV during a 5-day high-throughput multidisease community health campaign in May 2012 that recruited two-thirds of the population. We aggregated individual-level VL results into population VL metrics including the proportion of individuals with an undetectable VL and compared these VL metrics to those we previously reported for this geographic region in 2011. Results:In 2012, 223 of 2179 adults were HIV-seropositive adults (10%). Overall, among 208 of 223 HIV-seropositive adults in whom VL was tested, 53% had an undetectable VL [95% confidence interval (CI): 46 to 60], up from 37% (95% CI: 30 to 45; P = 0.02) in 2011. Seven (3%) individuals had a VL of >100,000 copies/mL in 2012, down from 21 (13%) in 2011 (P = 0.0007). Mean log (VL) (geometric mean) was 3.18 log (95% CI: 3.06 to 3.29 log) in 2012, down from 3.62 log (95% CI: 3.46 to 3.78 log) in 2011 (P < 0.0001). Similar reductions in population VL were seen among men and women. Conclusions:Reductions in population VL metrics and a substantial increase in the proportion of persons with an undetectable VL were observed in a rural Ugandan community from 2011 to 2012. These findings from a resource-limited setting experiencing rapid ART scale-up may reflect a population-level effectiveness of expanding ART access.

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda

Background Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up. Methods Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing. Findings Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451–716). Observed ART delivery cost was

Resistance patterns and response to entecavir intensification among HIV-HBV-coinfected adults with persistent HBV viremia.

628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of

Predictors of Retention in Hiv Care Among Youth (15–24) in a Universal Test-and-treat Setting in Rural Kenya

529/

A post-transcriptional regulatory switch in polypyrimidine tract-binding proteins reprograms alternative splicing in developing neurons

445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by

Effect of long-term highly active antiretroviral therapy in restoring HIV-induced abnormal B-lymphocyte function

100–200 ppy. Costs in a maximally efficient scale-up model were