Modeling of expanding antiretroviral treatment to all HIV-infected adults already in care in San Francisco predicts reductions in new HIV infection at 5 years of 59% among men who have sex with men. Addition of annual HIV testing for men who have sex with men to universal treatment decreases new infections by 76%.

Background

At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Francisco's community viral load (CVL) as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004-2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART) coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections.

Methodology/principal findings

We used San Francisco's HIV/AIDS surveillance system to examine the trends in CVL. Mean CVL was calculated as the mean of the most recent viral load of all reported HIV-positive individuals in a particular community. Total CVL was defined as the sum of the most recent viral loads of all HIV-positive individuals in a particular community. We used Poisson models with robust standard errors to assess the relationships between the mean and total CVL and the primary outcome: annual numbers of newly diagnosed HIV cases. Both mean and total CVL decreased from 2004-2008 and were accompanied by decreases in new HIV diagnoses from 798 (2004) to 434 (2008). The mean (p = 0.003) and total CVL (p = 0.002) were significantly associated with new HIV cases from 2004-2008.

Conclusions/significance

Reductions in CVL are associated with decreased HIV infections. Results suggest that wide-scale ART could reduce HIV transmission at the population level. Because CVL is temporally upstream of new HIV infections, jurisdictions should consider adding CVL to routine HIV surveillance to track the epidemic, allocate resources, and to evaluate the effectiveness of HIV prevention and treatment efforts.

In this article, we describe a process of the San Francisco collaboration to select optimal measures of linkage to care in response to the Enhanced Comprehensive HIV Prevention Planning program of the Centers for Disease Control and Prevention and to understand the implications of measure selection and the challenges of accessing data sources to measure outcomes along the HIV care continuum. Challenges identified are the variety of definitions of linkage to care and the nonintegrative nature of the multiple data systems necessary to measure linkage to care and other continuum outcomes. The choice of linkage measures, which at the extremes is a choice between higher-resolution measures based on clinical visit data in a subset of patients vs. a lower-resolution proxy measure based on surveillance data, has key implications. Choosing between the options needs to be informed by the primary use of the measure. For representing trends in the overall performance and response to interventions, more generalizable measures based on surveillance data are optimal. For identifying barriers to linkage to care for specific populations and potential intervention targets within the linkage process, higher-resolution measures of linkage that include clinical, laboratory, and social work visit information are optimal. Cataloging the different data systems along the continuum and observations of challenges of data sharing between the systems highlighted the promise of integrated data management systems that span HIV surveillance and care systems. Such integrated data management systems would have the ability to support detailed investigation and would provide simplified data to match newly developed, cross-agency Health and Human Service measures of HIV care continuum outcomes.

Episodic drug use and binge drinking are associated with HIV risk among substance-using men who have sex with men (SUMSM), yet no evidence-based interventions exist for these men. We adapted personalized cognitive counseling (PCC) to address self-justifications for high-risk sex among HIV-negative, episodic SUMSM, then randomized men to PCC (n = 162) with HIV testing or control (n = 164) with HIV testing alone. No significant between-group differences were found in the three primary study outcomes: number of unprotected anal intercourse events (UAI), number of UAI partners, and UAI with three most recent non-primary partners. In a planned subgroup analysis of non-substance dependent men, there were significant reductions in UAI with most recent non-primary partners among PCC participants (RR = 0.56; 95 %CI 0.34-0.92; P = 0.02). We did not find evidence that PCC reduced sexual risk behaviors overall, but observed significant reductions in UAI events among non-dependent SUMSM. PCC may be beneficial among SUMSM screening negative for substance dependence.

Background

Because tenofovir alafenamide (TAF) leads to significantly lower plasma tenofovir concentrations than tenofovir disoproxil fumarate (TDF) and is a stronger substrate for P-glycoprotein (P-gp) than TDF, TAF could lead to decreased central nervous system (CNS) tenofovir exposure than TDF. We aimed to determine if switching from TDF to TAF increases the risk of neuronal injury, by quantifying plasma levels of neurofilament light protein (NfL), a sensitive marker of neuronal injury in HIV CNS infection.

Methods

Plasma NfL concentration was measured at baseline, week 24, and week 84 in stored plasma samples from 416 participants (272 switching to elvitegravir (E)/cobicistat (C)/emtricitabine (F)/TAF and 144 continuing E/C/F/TDF) enrolled in the randomized, active-controlled, multicenter, open-label, noninferiority Gilead GS-US-292-0109 trial.

Results

While plasma NfL levels in both groups were within the normal range, we found a small but significant decrease in the E/C/F/TAF arm after 84 weeks from a geometric mean of 9.3 to 8.8 pg/mL (5.4% decline, 95% CI 2.0-8.4, p = 0.002). This change was significantly different (p = 0.001) from that of the E/C/F/TDF arm, in which plasma NfL concentration changed from 9.7 pg/mL at baseline to 10.2 pg/mL at week 84 (5.8% increase, 95% CI -0.8-12.9, p = 0.085). This increase is in line with what could be expected in normal ageing. Plasma NfL concentrations significantly correlated with age. No correlation was found between plasma NfL and serum creatinine.

Conclusions

We found no biomarker evidence of CNS injury when switching from TDF to TAF. It is unclear whether the small decrease in plasma NfL found after switch to TAF is of any clinical relevance, particularly with plasma NfL levels in both arms remaining within the limits found in HIV-negative controls. These results indicate that switching from TDF to TAF appears safe with regard to neuronal injury.

Background

Non-dependent alcohol and substance use patterns are prevalent among men who have sex with men (MSM), yet few effective interventions to reduce their substance use are available for these men. We evaluated whether an adapted brief counseling intervention aimed at reducing HIV risk behavior was associated with secondary benefits of reducing substance use among episodic substance-using MSM (SUMSM).

Methods

326 episodic SUMSM were randomized to brief Personalized Cognitive Counseling (PCC) intervention with rapid HIV testing or to rapid HIV testing only control. Both arms followed over 6 months. Trends in substance use were examined using GEE Poisson models with robust standard errors by arm. Reductions in frequency of use were examined using ordered logistic regression.

Results

In intent-to-treat analyses, compared to men who received rapid HIV testing only, we found men randomized to PCC with rapid HIV testing were more likely to report abstaining from alcohol consumption (RR=0.93; 95% CI=0.89-0.97), marijuana use (RR=0.84; 95% CI=0.73-0.98), and erectile dysfunction drug use (EDD; RR=0.51; 95% CI=0.33-0.79) over the 6-month follow-up. PCC was also significantly associated with reductions in frequency of alcohol intoxication (OR=0.58; 95% CI=0.36-0.90) over follow-up. Furthermore, we found PCC was associated with significant reductions in number of unprotected anal intercourse events while under the influence of methamphetamine (RR=0.26; 95% CI=0.08-0.84).

Conclusion

The addition of adapted PCC to rapid HIV testing may have benefits in increasing abstinence from certain classes of substances previously associated with HIV risk, including alcohol and EDD; and reducing alcohol intoxication frequency and high-risk sexual behaviors concurrent with methamphetamine use.

Aims

To test aripiprazole for efficacy in decreasing use in methamphetamine-dependent adults, compared to placebo.

Design

Participants were randomized to receive 12 weeks of aripiprazole or placebo, with a 3-month follow-up and a platform of weekly 30-minute substance abuse counseling.

Setting

The trial was conducted from January 2009 to March 2012 at the San Francisco Department of Public Health.

Participants

Ninety actively using, methamphetamine-dependent, sexually active adults were recruited from community venues.

Measurements

The primary outcome was regression estimated reductions in weekly methamphetamine-positive urines. Secondary outcomes were study medication adherence [by self-report and medication event monitoring systems (MEMS)], sexual risk behavior and abstinence from methamphetamine.

Findings

Participant mean age was 38.7 years, 87.8% were male, 50.0% white, 18.9% African American, and 16.7% Latino. Eighty-three per cent of follow-up visits and final visits were completed. By intent-to-treat, participants assigned to aripiprazole had similar reductions in methamphetamine-positive urines as participants assigned to placebo [risk ratio (RR) 0.88, 95% confidence interval (CI): 0.66-1.19, P = 0.41]. Urine positivity declined from 73% (33 of 45 participants) to 45% (18 of 40) in the placebo arm and from 77% (34 of 44) to 44% (20 of 35) in the aripiprazole arm. Adherence by MEMS and self-report was 42 and 74%, respectively, with no significant difference between arms (MEMS P = 0.31; self-report P = 0.17). Most sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug, although participants randomized to aripiprazole reported more akathisia, fatigue and drowsiness (P < 0.05).

Conclusion

Compared with placebo, aripiprazole did not reduce methamphetamine use significantly among actively using, dependent adults.

We evaluated the relationship between frequency and number of substances used and HIV risk [ie, serodiscordant unprotected anal intercourse (SDUAI)] among 3173 HIV-negative substance-using MSM. Compared with nonusers, the adjusted odds ratio (AOR) for SDUAI among episodic and at least weekly users, respectively, was 3.31 [95% confidence interval (CI), 2.55 to 4.28] and 5.46 (95% CI, 3.80 to 7.84) for methamphetamine, 1.86 (95% CI, 1.51 to 2.29) and 3.13 (95% CI, 2.12 to 4.63) for cocaine, and 2.08 (95% CI, 1.68 to 2.56) and 2.54 (95% CI, 1.85 to 3.48) for poppers. Heavy alcohol drinkers reported more SDUAI than moderate drinkers [AOR, 1.90 (95% CI, 1.43 to 2.51)]. Compared with nonusers, AORs for using 1, 2, and ≥3 substances were 16.81 (95% CI, 12.25 to 23.08), 27.31 (95% CI, 18.93 to 39.39), and 46.38 (95% CI, 30.65 to 70.19), respectively. High-risk sexual behaviors were strongly associated with frequency and number of substances used.

Introduction

Randomized trials of new agents for HIV pre-exposure prophylaxis (PrEP) compare against emtricitabine and tenofovir disoproxil fumarate (F/TDF), without a placebo group. We used the well-characterized adherence-efficacy relationship for F/TDF to back-calculate the (non-PrEP) counterfactual background HIV incidence (bHIV) in a randomized trial of a novel PrEP agent and estimate comparative efficacy (to counterfactual bHIV).

Methods

The DISCOVER trial (ClinicalTrials.gov: NCT02842086) randomized 5387 men who have sex with men (MSM) and transgender women who have sex with men and demonstrated non-inferiority of emtricitabine and tenofovir alafenamide (F/TAF) to F/TDF (HIV incidence rate ratio [IRR] 0·47, 95% CI: 0·19 to 1.15). Tenofovir diphosphate (TFV-DP) levels in dried blood spots (DBS) were assessed for all diagnosed with HIV and in a random 10% of the cohort. We used a Bayesian model with a diffuse prior distribution, derived from established data relating tenofovir diphosphate levels to HIV prevention efficacy. This prior, combined with the F/TDF seroconversion rate and tenofovir diphosphate levels in DISCOVER, yielded Bayesian inferences on the counterfactual bHIV.

Results

There were six versus 11 postbaseline HIV infections (0.14 vs. 0.25/100 person-years [PY]) on F/TAF and F/TDF respectively. Of the 11 on F/TDF, 10 had low, none had medium and one had high tenofovir diphosphate levels; among HIV-negative controls, 5% of the person-time years had low, 9% had medium and 86% had high TFV-DP levels. A non-informative prior distribution for counterfactual bHIV, combined with the prior for TFV-DP level-efficacy relationship, yielded a posterior counterfactual bHIV of 3·4 infections/100 PY (0.80 Bayesian credible interval [CrI] 1·9 to 5·9), which suggests a median HIV efficacy of 96% (0.95 CrI [88% to 99%]) for F/TAF and 93% (0.95 CrI [87% to 96%]) for F/TDF compared to bHIV.

Conclusions

Based on the established connection of drug concentrations to PrEP prevention efficacy, a Bayesian framework can be used to estimate a synthetic non-PrEP control group in randomized, active-controlled PrEP trials that include a F/TDF-comparator group.

Episodic (less than weekly) drug use and binge drinking increase HIV-related sexual risk behaviors among men who have sex with men (MSM), yet no evidence-based interventions exist for these men. We describe an adaptation process of the Personalized Cognitive Counseling (PCC) intervention for utilization with high-risk, HIV-negative episodic, substance-using MSM. Participants (N = 59) were racially diverse, and reported unprotected anal intercourse and concurrent binge drinking (85%), use of poppers (36%), methamphetamine (20%) and cocaine (12%). Semi-structured interviews with 20 episodic, substance-using MSM elicited sexual narratives for engaging in unprotected anal intercourse while using alcohol or drugs. Emergent qualitative themes were translated into self-justifications and included in a revised PCC self-justification elicitation instrument (SJEI). The adapted SJEI was pretested with 19 episodic, substance-using MSM, and the final adapted PCC was pilot-tested for acceptability and feasibility with 20 episodic, substance-using MSM. This process can be used as a roadmap for adapting PCC for other high-risk populations of MSM.