Brief Report

BackgroundThe World Health Organization defines HIV virologic failure as 2 consecutive viral loads >1000 copies/mL, measured 3-6 months apart, with interval adherence support. We sought to empirically evaluate these guidelines using data from an observational cohort.SettingThe Uganda AIDS Rural Treatment Outcomes study observed adults with HIV in southwestern Uganda from the time of antiretroviral therapy (ART) initiation and monitored adherence with electronic pill bottles.MethodsWe included participants on ART with a detectable HIV RNA viral load and who remained on the same regimen until the subsequent measurement. We fit logistic regression models with viral resuppression as the outcome of interest and both initial viral load level and average adherence as predictors of interest.ResultsWe analyzed 139 events. Median ART duration was 0.92 years, and 100% were on a nonnucleoside reverse-transcriptase inhibitor-based regimen. Viral resuppression occurred in 88% of those with initial HIV RNA <1000 copies/mL and 42% if HIV RNA was >1000 copies/mL (P <0.001). Adherence after detectable viremia predicted viral resuppression for those with HIV RNA <1000 copies/mL (P = 0.011) but was not associated with resuppression for those with HIV RNA >1000 copies/mL (P = 0.894; interaction term P = 0.077).ConclusionsAmong patients on ART with detectable HIV RNA >1000 copies/mL who remain on the same regimen, only 42% resuppressed at next measurement, and there was no association between interval adherence and viral resuppression. These data support consideration of resistance testing to help guide management of virologic failure in resource-limited settings

Increasing Prevalence of HIV Pretreatment Drug Resistance in Women But Not Men in Rural Uganda During 2005-2013

The prevalence of HIV pretreatment drug resistance (PDR) is increasing in sub-Saharan Africa. We sought to describe correlates of PDR and evaluate effects of PDR on clinical outcomes in rural Uganda. We analyzed data from the Uganda AIDS Rural Treatment Outcomes study, a cohort of antiretroviral therapy (ART)-naive adults with HIV (2005-2015). We performed resistance testing on pre-ART specimens. We defined PDR as any World Health Organization (WHO) 2009 surveillance drug resistance mutation and classified PDR level using the Stanford algorithm. We fit unadjusted and sex-stratified log binomial regression and Cox proportional hazard models to identify correlates of PDR and the impact of PDR on viral suppression, loss to follow-up (LTFU), and death. We analyzed data from 738 participants (median age 33 years, 69% female). Overall, prevalence of PDR was 3.5% (n = 26), owing mostly to resistance to non-nucleoside reverse transcriptase inhibitors. PDR increased over time in women (1.8% in those enrolling in clinic in 2001-2006, vs. 7.0% in 2007-2013; p = 0.006), but not in men (1.15% vs. 0.72%, p = 0.737). Lower pre-ART log10 HIV RNA was also associated with higher prevalence of PDR. We identified longer time to viral suppression among those with PDR compared with without PDR (0.5 and 0.3 years, respectively, p = 0.023), but there was no significant relationship with mortality or LTFU (p = 0.139). We observed increasing rates of PDR in women in southwestern Uganda. Implications of this trend, particularly to prevention of mother-to-child transmission programs in the region, require attention due to delayed viral suppression among those with PDR

1498. Geographic differences in weight change on dolutegravir: a prospective cohort study

Background: People with HIV (PWH) on integrase inhibitors may be at increased risk of excess weight gain, but it is unclear if this risk is consistent across settings. Our study objective was to compare weight change over 48 weeks among PWH in Uganda and South Africa.Figure 1.Mean weight change (kg) over 48 weeks among DISCO participants overall (A), among men (B), and among women (C). Methods: The Population Effectiveness of Dolutegravir Implementation in Sub-Saharan Africa (DISCO) study is a prospective observational cohort of PWH in routine clinical care at public-sector HIV clinics in Uganda and South Africa. Inclusion criteria were as follows: PWH >18 years old, on NNRTI-based first-line ART for >6 months, and switched to tenofovir disoproxil fumarate, lamivudine, and dolutegravir) by clinic staff. We measured the primary outcomes of weight (in kilograms [kg]) and waist circumference (WC, in centimeters [cm]) at enrollment, 24 weeks, and 48 weeks after switch. The primary outcomes were (1) weight change (kg) and (2) change in WC (cm). We used a linear mixed-effect regression model, adjusted for age, sex, education, duration on ART, and the interaction of study site and visit, to estimate weight. Results: 428 individuals in Uganda and 387 in South Africa had data available. The mean weight change over 48 weeks was 0.6 kg [95% CI: 0.1-1.0] in Uganda compared to 2.9 kg [2.4-3.4] in South Africa (p< 0.001); men had significantly smaller mean weight changes than women did in both countries (Figure 1). After adjustment, PWH in South Africa gained significantly more weight than those in Uganda. In participants with available waist data (277 in Uganda and 402 in South Africa), the mean change in WC was significantly greater among those in South Africa (2.3 cm [1.4-3.2]) than those in Uganda (0.8 cm [0.0-1.5]) (p< 0.017). Conclusion: PWH in South Africa experienced greater weight gain than in Uganda, suggesting substantial heterogeneity in this risk across settings. Strategies to address obesity risk in PWH should account for regionality. Disclosures: W D Francois Venter, MD, FCP, PhD, Gilead Sciences: Grant/Research Support|South African Medical Research Council: Grant/Research Support|Unitaid: Grant/Research Support|USAID: Grant/Research Support|ViiV Healthcare: Grant/Research Support Mark J Siedner, MD, MPH, Viiv Healthcare: Grant/Research Suppor

Population Effectiveness of Dolutegravir Implementation in Uganda - A Prospective Observational Cohort Study (DISCO): 48-week Results.

BACKGROUND: Tenofovir/lamivudine/dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen for people with HIV (PWH), including those who were previously virologically suppressed on non-nucleoside reverse transcriptase inhibitors (NNRTIs). We sought to estimate the real-world effectiveness of the TLD transition in Ugandan public-sector clinics. METHODS: We conducted a prospective cohort study of PWH ≥18 years who were transitioned from NNRTI-based ART to TLD. Study visits were conducted on the day of TLD transition and 24- and 48- weeks later. The primary endpoint was viral suppression (500 copies/mL. RESULTS: We enrolled 500 participants (median age of 47 years; 41% women). At 48-weeks after TLD transition, 94% of participants were in care with a VL 500 copies/mL. No incident resistance to DTG was identified. Few participants (2%, n = 9/500) discontinued TLD due to adverse events. CONCLUSIONS: High rates of viral suppression, high tolerability, and lack of emergent drug resistance support use of TLD as the preferred first-line regimen in the region

Seemingly Unrelated Regression Analysis of the Cost and Health-Related Quality of Life Outcomes of the REVAMP Randomized Clinical Trial

Objective: This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. Methods: We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. Results: For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. Conclusion: Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial

Genome-wide approaches to elucidate evolution of sex determination systems and sex determining genes in fish

[YG: Invited Keynote Lecture]International audienc