Clinical and Virological Outcomes of TB/HIV Coinfected Patients Treated With Dolutegravir-Based HIV Antiretroviral Regimens: Programmatic Experience From Botswana Background: Dolutegravir (DTG) has recently been recommended as a preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. However, potential drug interactions between DTG and rifampicin remain a clinical and public health concern. Methods: We analyzed HIV and Tuberculosis (TB) treatment outcomes of HIV-infected patients concomitantly receiving rifampicin- and DTG-based regimens under programmatic conditions in Botswana. The outcomes of interest were successful TB treatment and viral load suppression. We used multivariable logistic models to determine predictors for each outcome of interest. Results: A total of 1225 patients were included in the analysis to evaluate predictors of successful TB outcome. Among patients on DTG and non-DTG regimens, 90.9% and 88.3% achieved favorable TB treatment outcomes, respectively. Of those who received DTG-based regimen; 44% received once-daily dosing and 53% twice-daily dosing. We found that DTG was associated with favorable TB treatment outcome (adjusted odds ratio = 1.56; 95% confidence interval = 1.06 to 2.31), after adjusting for age, gender, and CD4 cell counts. High rates of viral load suppression were found across all antiretroviral therapy (ART) regimen categories (>92% for all). We did not find an independent association between DTG and viral suppression after adjustment of other covariates. Conclusions: The use of DTG-based ART regimens in patients coinfected with TB and HIV lead to favorable TB and HIV treatment outcomes, comparable to those achieved with alternative ART regimens. Our results provide reassurance to TB and HIV programs about the overall programmatic concomitant use of these first-line treatment regimens for the management of HIV and TB coinfected patients.

Internalized HIV Stigma Is Associated With Concurrent Viremia and Poor Retention in a Cohort of US Patients in HIV Care Background: The relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data. Setting: Center for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study. Methods: Beginning in February 2016, we administered a yearly, validated 4-item internalized HIV stigma scale (response scale 1 = strongly disagree to 5 = strongly agree, Cronbach's alpha 0.91) at 7 CNICS sites and obtained cohort data through November 2017. We compared mean stigma levels by sociodemographic characteristics and used multivariable logistic regression, controlling for the same sociodemographic covariates, to evaluate the association between mean stigma and (1) concurrent viremia; (2) missed visits; and (3) poor visit constancy. We used inverse probability weighting (IPW) to account for differences between patients who did and did not undergo stigma assessment. Results: Of 13,183 CNICS patients, 6448 (49%) underwent stigma assessment. Mean stigma was 1.99 (SD 1.07), and 28.6% agreed/strongly agreed with at least 1 stigma question. Patients younger than 50 years, racial/ethnic minorities, cis-women, and heterosexuals had higher mean stigma. Mean stigma score was associated with concurrent viremia [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI): 1.02 to 1.25, P 0.02], missed visits (AOR 1.10, 95% CI: 1.02 to 1.19, P 0.01), and poor visit constancy, although the effect on visit constancy was attenuated in the IPW model (AOR 1.05, 95% CI: 0.98 to 1.13, P 0.17). Conclusions: Higher internalized HIV stigma had a modest but statistically significant association with concurrent viremia and poor retention in care. Further inquiry with prospective analyses is warranted.

Treatment Adherence Among Persons Receiving Concurrent Multidrug-Resistant Tuberculosis and HIV Treatment in KwaZulu-Natal, South Africa Background: Success in multidrug-resistant tuberculosis (MDR-TB) and HIV treatment requires high medication adherence despite high pill burdens, frequent adverse events, and long treatment duration, which may jeopardize adherence. We prospectively compared MDR-TB/HIV-coinfected persons to those with MDR-TB alone to determine the impact of concurrent treatment on adherence and outcomes. Methods: We assessed medication adherence monthly using 3-day recall, 30-day recall, and visual analog scale and examined adherence to monthly study visits (months 0–12). We determined the proportion of participants fully adherent (no reported missed doses) to MDR-TB vs. HIV treatment by each measure. We assessed the association of medication and clinic visit adherence with MDR-TB treatment success (cure or completion, 18–24 months) and HIV virologic suppression. Results: Among 200 patients with MDR-TB, 63% were women, median age was 33 years, 144 (72%) were HIV-infected, and 81% were receiving antiretroviral therapy (ART) at baseline. Adherence to medications (81%–98% fully adherent across all measures) and clinic visits (80% missed ≤1 visit) was high, irrespective of HIV status. Adherence to ART was significantly higher than to MDR-TB treatment by all self-reported measures (3-day recall: 92% vs. 84%, respectively; P = 0.003). In multivariable analysis, the adjusted risk ratio of unsuccessful MDR-TB treatment increased with every missed visit: 1.50, 2.25, and 3.37 for unsuccessful treatment, for 1, 2, and ≥3 missed visits. Conclusions: Adherence to ART was higher than to MDR-TB treatment among persons with MDR-TB/HIV coinfection. Missed clinic visits may be a simple measure for identifying patients at risk of unsuccessful MDR-TB treatment outcome.

A Gap Between Willingness and Uptake: Findings From Mixed Methods Research on HIV Prevention Among Black and Latina Transgender Women Background: Black and Latina transgender women (BLTW) face significant HIV disparities with estimated HIV prevalence up to 50% and annual incidence rates as high as 2.8 per 100 person-years. However, few studies have evaluated the acceptability and uptake of high-impact HIV prevention interventions among BLTW. Setting: Data collection took place in Baltimore, MD and Washington, DC from May 2015 to May 2017. Methods: This mixed methods study included quantitative interviewer-administered surveys, key informant interviews, and focus group discussions. Rapid HIV testing followed each survey. Logistic regression models tested associations between legal gender affirmation (ie, desired name and gender marker on identity documents), transgender pride, history of exchange sex, HIV risk perception, and willingness to take pre-exposure prophylaxis (PrEP). Transcripts of qualitative data were coded to identify common themes related to engagement in HIV prevention. Results: Among 201 BLTW, 56% tested HIV-positive and 87% had heard of PrEP. Only 18% who had heard of PrEP had ever taken it. Of the 72 self-reported HIV-negative or status-unknown BLTW who had never taken PrEP, 75% were willing to take it. In multivariable analyses, history of exchange sex was associated with willingness to take PrEP, whereas greater HIV knowledge and transgender pride were associated with lower likelihood of willingness to take PrEP. Concern about drug interactions with hormone therapy was the most frequently reported barrier to PrEP uptake. Conclusions: Noting the disconnect between PrEP willingness and uptake among BLTW, HIV prevention programs could bridge this gap by responding to identified access barriers and incorporating community-derived strategies.

Project Shikamana: Community Empowerment-Based Combination HIV Prevention Significantly Impacts HIV Incidence and Care Continuum Outcomes Among Female Sex Workers in Iringa, Tanzania Objective: To determine the impact of a community empowerment model of combination HIV prevention (Project Shikamana) among female sex workers (FSW) in Iringa, Tanzania. Methods: We conducted a 2-community randomized trial. Intervention elements included the following: (1) Community‐led drop‐in center and mobilization activities; (2) venue-based peer education, condom distribution, and HIV testing; (3) peer service navigation; (4) provider sensitivity trainings; and (5) SMS reminders. We used time-location sampling to enroll 496 FSW and conducted a survey and blood draws to screen for HIV and assess viral load at 0 and 18 months. We conducted an intent-to-treat analysis using logistic and Poisson regression and inverse probability weighting for primary outcomes. Results: The analysis included 171 HIV-positive and 216 HIV-negative FSW who completed baseline and 18-month study visits. Participants in the intervention were significantly less likely to become infected with HIV at 18-month follow-up (RR 0.38; P = 0.047), with an HIV incidence of 5.0% in the intervention vs. 10.4% control. Decreases in inconsistent condom use over time were significantly greater in the intervention (72.0%–43.6%) vs. control (68.8%–54.0%; RR 0.81, P = 0.042). At follow-up, we observed significant differences in behavioral HIV care continuum outcomes, and positive, but nonsignificant, increases in viral suppression (40.0%–50.6%) in the intervention vs. control (35.9%–47.4%). There was a strong association of between higher intervention exposure and HIV outcomes including viral suppression. Conclusions: Project Shikamana is the first trial of community empowerment-based combination prevention among FSW in Africa to show a significant reduction in HIV incidence warranting its broader implementation and evaluation.

Short- and Long-Term Pharmacologic Measures of HIV Pre-exposure Prophylaxis Use Among High-Risk Men Who Have Sex With Men in HPTN 067/ADAPT Background: The effectiveness of oral emtricitabine (FTC)/tenofovir (TFV) disoproxil fumarate–based HIV pre-exposure prophylaxis (PrEP) depends on adherence. Pharmacologic measures help interpret patterns and predictors of PrEP adherence. Setting: We analyzed data from the subsample of men who have sex with men enrolled in HPTN 067/ADAPT in Bangkok, Thailand, and Harlem, NY, U.S. Methods: After a 5-week directly observed therapy period, participants were randomized to daily, time-driven, or event-driven PrEP. Follow-up occurred at weeks 4, 12, and 24 after randomization. Plasma and hair FTC/TFV levels indicated short- and long-term PrEP use, respectively. Electronic pill bottle data (Wisepill) were collected weekly. Pearson correlation coefficients between PrEP use measures were calculated; linear mixed models assessed predictors of plasma and hair drug concentrations. Results: Among 350 participants (median age: 31 years, interquartile range: 25–38), 49.7% were from Harlem, half had less than college education, and 21% reported heavy alcohol use. In multivariable models, being enrolled in Harlem, being in non–daily arms, and having less than college education were associated with lower hair FTC/TFV concentrations; heavy alcohol use was associated with higher concentrations. Similar results were found for plasma concentrations by site and arm, but older age and greater number of sex partners were associated with higher concentrations. Hair and plasma FTC/TFV concentrations were moderately correlated with Wisepill data (r ≥ 0.29) across visits. Conclusions: In HPTN067, plasma, hair, and Wisepill data correlated with one another and served as complementary adherence measures. Site, arm, education, age, alcohol, and sexual behavior influenced patterns of adherence.

HIV Seroconversion in the Era of Pharmacologic Prevention: A Case–Control Study at a San Francisco STD Clinic Background: The comparative effectiveness of pre- and post-exposure prophylaxis (PrEP and PEP) for men who have sex with men (MSM) is unclear. Setting: We conducted a case–control study of MSM who were initially HIV-uninfected during September 1, 2012–June 30, 2016 at San Francisco's only municipal sexually transmitted diseases (STDs) clinic. Methods: Each case was matched with up to 3 controls based on age, baseline visit date, and follow-up time. The primary dependent variable was HIV seroconversion; the primary independent variable was exposure to PrEP, PEP, or neither. Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals. Results: Of 638 MSM (161 cases and 477 controls), 137 reported ever taking PrEP, 98 reported taking PEP-only, and 403 took neither. PrEP takers had more non-HIV sexually transmitted diseases during the analysis (72.3% vs. 55.1% vs. 42.4% P < 0.01) and were more likely to report receptive anal sex in the past 3 months (86.5% vs. 80.4% vs. 73.0%; P < 0.01). In the adjusted model, PrEP was associated with lower odds of HIV seroconversion (odds ratio 0.24; 95% confidence interval: 0.13 to 0.46) while PEP use had no effect on HIV acquisition compared with taking neither. Conclusions: MSM who ever used PrEP demonstrated equal or higher sexual risk compared with those using neither PrEP nor PEP but had 76% lower odds of HIV seroconversion. MSM who used PEP but never PrEP were no less likely to seroconvert than those using neither. MSM should be offered PrEP. PEP users with ongoing risk of HIV infection should be connected to PrEP after PEP.

HPTN 067/ADAPT: Correlates of Sex-Related Pre-exposure Prophylaxis Adherence, Thai Men Who Have Sex With Men, and Transgender Women, 2012–2013 Background: We identified correlates of sex-related pre-exposure prophylaxis (PrEP) adherence in HPTN067/ADAPT, a phase 2, open-label feasibility study of daily and nondaily regimens of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based PrEP, among Thai men who have sex with men (MSM), and transgender women (TGW), Bangkok. Methods: Participants were randomly assigned to one of three self-administered dosing regimens for 24 weeks: daily, time-driven, or event-driven. Demographic and behavioral information was obtained at screening. Pill-container opening was recorded with electronic dose monitoring, and self-reported information on PrEP use, sex events, and substance use was obtained during weekly interviews to confirm dose data. Sex-related PrEP adherence was calculated as the proportion of sex events covered by PrEP use (at least one tablet taken within 4 days before sex and at least one tablet taken within 24 hours after sex) to total sex events. We used multivariate modeling with sex event as the unit of analysis to evaluate correlates associated with sex-related PrEP adherence. Results: Among 178 MSM and TGW, sex-related PrEP adherence was similar in the daily and time-driven arms (P = 0.79), both significantly greater than the event-driven arm (P = 0.02 compared to daily). Sex-related PrEP adherence by those reporting stimulant use (74.2%) was similar to those reporting other nonalcohol drug use (76.3%, P = 0.80), but lower than those reporting no substance use (84.6%, P = 0.04). In a multivariable model, randomization to the event-driven arm, a higher prestudy number of reported sex events, and use of stimulant drugs were associated with significantly lower sex-related PrEP adherence. Conclusion: Adherence was influenced by treatment schedule and adversely affected by nonalcoholic substance use. Regardless of these factors, Thai MSM and TGW maintained high adherence levels to oral PrEP dosing regimens and coverage of sexual exposures.

Transition Pathways Out of Pediatric Care and Associated HIV Outcomes for Adolescents Living With HIV in South Africa Background: Research on adolescent transitions out of pediatric HIV care has focused on high-income countries, with limited understanding of transitions in sub-Saharan Africa's public health sector. Methods: Patient file data were extracted through December 2017 for all 10- to 19-year olds ever initiated on antiretroviral therapy in a health district of the Eastern Cape, South Africa (n = 951). Pathways in HIV care were identified by tracing movements across facility care types and levels. Associations between pathways and viral failure, mortality, loss to follow-up, and viral load change were tested in sequential multivariable regressions. Analyses controlled for sociodemographic and treatment-related variables. Thematic analyses of semistructured health care provider interviews identified transition support at included facilities. Results: Only 57.8% of adolescents had initiated antiretroviral therapy in pediatric care, and 20.4% of the total cohort had transitioned out of pediatric HIV care. Among the 42.2% who had initiated in nonpediatric care, 93.8% remained exclusively in nonpediatric care. Median age at first transition was 14 years. Two main pathways were identified: classical transition to adult HIV care (43.3%) and down referral transition to primary health care clinics (56.7%). Across pathways, 27.3% experienced cyclical transition or repeated movement between pediatric and nonpediatric care. Independent of covariates, adolescents with down referral transition were less likely to demonstrate viral failure (adjusted odds ratio, 0.21; 95% confidence interval: 0.10 to 0.42; P < 0.001). Mortality and loss to follow-up were not associated with either pathway. Median posttransition viral load change was not clinically significant (median, 0.00; interquartile range: 0.00–0.35) or associated with transition pathways. Health care providers described informal “protocols” for mitigating risk of negative posttransition HIV outcomes. Conclusions: This study proposes a contextually relevant model for transitions out of pediatric HIV care in South Africa. Feasible, scalable “protocols” may mitigate risk of worsening posttransition HIV outcomes.

Brief Report: Outcome of Acute Hepatitis B Virus Infection in HIV-1–Infected Patients: Possible Factors Associated With Resolution or Chronicity Background: HIV-1 infection impairs cellular immunity, causing a detrimental effect on the natural course of hepatitis B virus (HBV) infection. HBV vaccination is less effective in HIV-1–infected patients. This study aimed to gain insight into HIV-1 infection with persistence of hepatitis B surface antigen (HBsAg) defining chronic hepatitis B infection (CBI) after a primary infection and the possible associated factors. Setting: Division of Infectious Diseases, San Raffaele Hospital, Italy. Methods: This retrospective study analyzed HIV-1–infected patients diagnosed with acute hepatitis B infection (AHB) based on clinical or laboratory records. CBI was defined as a positive HBsAg result recorded >6 months after an AHB diagnosis. Multivariate logistic regression was applied to assess factors (evaluated at AHB diagnosis) that were associated with CBI. Results: Of 63 HIV-1–infected patients with AHB, 23 (36.5%) developed CBI. On multivariate analysis, CBI risk was less likely in patients with HIV-RNA of >50 copies/mL (adjusted odds ratio = 0.03, 95% confidence interval: 0.001 to 0.58, P = 0.021). Dually acting antiretroviral treatment, including one or more drugs active against HIV/HBV (lamivudine, emtricitabine, and tenofovir), seemed to be protective in terms of the clinical outcome of CBI (adjusted odds ratio = 0.07, 95% confidence interval: 0.01 to 1.02, P = 0.050). Among the 23 patients with CBI, 15 (65.2%) lost the hepatitis B e-antigen, while 11 (47.8%) had HBsAg seroclearance during follow-up. Conclusions: In HIV-1–infected subjects with AHB, the persistence of HBsAg seemed to occur frequently. Factors associated with a lower CBI risk were detectable HIV load and the use of dually acting antiretroviral treatment during AHB.