Jonathan E. Volk

No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting

Referrals for and initiation of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection increased dramatically in a large clinical practice setting since 2012. Despite high rates of sexually transmitted infections among PrEP users and reported decreases in condom use in a subset, there were no new HIV infections in this population.

Preexposure Prophylaxis for HIV Prevention in a Large Integrated Health Care System: Adherence, Renal Safety, and Discontinuation.

Background:Placebo-controlled and open-label studies have demonstrated the safety and efficacy of daily oral preexposure prophylaxis (PrEP) in preventing HIV infection, but data are limited on real-world PrEP use. Methods:We conducted a cohort study from July 2012 through June 2015 of Kaiser Permanente Northern California members initiating PrEP. We assessed pharmacy refill adherence and discontinuation, decreases in estimated glomerular filtration rate (eGFR), and sexually transmitted infection (STI)/HIV incidence. Results:Overall, 972 individuals initiated PrEP, accumulating 850 person-years of PrEP use. Mean adherence was 92% overall. Black race/ethnicity [adjusted risk ratio (aRR) 3.0; 95% confidence interval: 1.7 to 5.1, P < 0.001], higher copayments (aRR 2.0; 1.2 to 3.3, P = 0.005), and smoking (aRR 1.6; 1.1 to 2.3, P = 0.025) were associated with <80% adherence. PrEP was discontinued by 219 (22.5%); female sex (aRR 2.6; 1.5 to 4.6, P < 0.001) and drug/alcohol abuse (aRR 1.8; 1.3 to 2.6, P = 0.002) were associated with discontinuation. Among 909 with follow-up creatinine testing, 141 (15.5%) had an eGFR <70 mL·min−1·1.73 m−2 and 5 (0.6%) stopped PrEP because of low eGFR. Quarterly STI positivity was high and increased over time for rectal chlamydia (P < 0.001) and urethral gonorrhea (P = 0.012). No HIV seroconversions occurred during PrEP use; however, 2 occurred in individuals who discontinued PrEP after losing insurance coverage. Conclusions:PrEP adherence was high in clinical practice, consistent with the lack of HIV seroconversions during PrEP use. Discontinuation because of renal toxicity was rare. STI screening every 6 months, as recommended by current guidelines, may be inadequate. Strategies are needed to increase PrEP access during gaps in insurance coverage.

Why HIV Infections Have Increased Among Men Who Have Sex with Men and What to Do About It: Findings from California Focus Groups

A resurgence of sexual risk taking, STDs, and HIV incidence has been reported among men who have sex with men (MSM) in several countries. We asked 113 MSM in 12 focus groups conducted in five California cities to identify factors leading to increased risk taking and assess prevention messages to reduce risk in this population. Participants perceived that HIV risk taking has increased because (1) HIV is not the threat it once was due to more effective therapies, (2) MSM communicate less about HIV, and social support for being safe has decreased, and (3) community norms have shifted such that unsafe sex is more acceptable. The prevention messages ranked most likely to motivate risk reduction encouraged individuals to seek social support from friends. Themes ranked least likely to succeed were those that described the negative consequences of HIV or reinforced existing safer sex messages.

Incident Hepatitis C Virus Infections Among Users of HIV Preexposure Prophylaxis in a Clinical Practice Setting

To the Editor—Although hepatitis C virus (HCV) is most efficiently transmitted through percutaneous routes, sexual transmission of HCV is well documented among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) [1–4]. Sexual transmission of HCV also occurs among HIV-uninfected MSM [5, 6], with many reporting sexual contact with HIV-infected partners [7]. The Centers for Disease Control and Prevention recommends the use of preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate for the prevention of HIV infection among at-risk MSM, with screening for HCV prior to PrEP initiation [8]. However, ongoing monitoring for HCV infection among PrEP users is not recommended. Here, we report on 2 incident HCV infections diagnosed among 485 HIV-uninfected MSM receiving PrEP at the Kaiser Permanente San Francisco Medical Center between February 2011 and December 2014. These infections occurred during 304 person-years of PrEP use, for an incidence rate of 0.7 per 100 person-years (95% confidence interval, .08–2.4). Patient 1 was a 46-year-old MSM who initiated PrEP in August 2013. From August 2013 through July 2014, he was diagnosed with 2 episodes of syphilis, rectal gonorrhea, and rectal chlamydia. In June 2014, the patient reported receptive anal intercourse without a condom with a partner who had a penile piercing. In July 2014, he also reported receptive anal intercourse with multiple male partners in a group setting. The patient denied injection drug use, tattooing, or body piercings. His alanine aminotransferase (ALT) level increased from normal at baseline to 50 U/L in July 2014 and 549 U/L in September 2014. He reported an increase in fatigue over the preceding 2 months, as well as migratory arthralgias in his bilateral ankles and knees and a dull left flank pain for several weeks. In September 2014, HCV antibody was positive and HCV RNA was detected at 6938 IU/mL. Further testing confirmed the presence of HCV genotype 4 with repeat HCV RNA that remained detectable. The patient is currently being monitored for possible spontaneous viral clearance. Patient 2 was a 37-year-old MSM who initiated PrEP in October 2013. Between October 2013 and November 2014, he was diagnosed with rectal chlamydia on 3 occasions, rectal gonorrhea on 2 occasions, and syphilis once. He denied injection drug use, tattooing, or body piercings. In March 2014, his ALT was newly elevated at 743 U/L, and he reported a 2-month history of nausea, weight loss, arthralgias, and fatigue. HCV antibody was positive, and HCV RNA was detected at 34.5 million IU/mL. Further testing confirmed the presence of HCV genotype 1 with a repeat HCV RNA of 2.8 million IU/mL. He was treated with 12 weeks of pegylated interferon monotherapy, resulting in a sustained virologic response. In both cases, no risk factors for HCV infection were reported other than sexual intercourse without condom use. These incident HCV infections suggest an important role for ongoing HCV monitoring for HIV-uninfected MSM receiving PrEP given the potential for sexual transmission in this population. Patients initiating PrEP should be counseled regarding the risk of sexually transmitted HCV.

Acceptability and feasibility of HIV self-testing among men who have sex with men in Peru and Brazil.

HIV self-testing has the potential to increase testing frequency and uptake. This pilot study assessed the feasibility and acceptability of HIV self-testing in a sample of sexually active men who have sex with men (MSM) in Peru and Brazil. Participants were trained to use a whole blood rapid HIV self-test and instructed to use the self-test monthly during this three-month study. Test acceptability was measured with self-reported use of the test at the one-month and three-month study visits, and test feasibility was assessed by direct observation of self-test administration at the final three-month visit. A total of 103 participants (52 in Peru and 51 in Brazil) were enrolled, and 86% completed the three-month study. Nearly all participants reported use of the self-test (97% at one-month and 98% at three-month visit), and all participants correctly interpreted the self-administered test results when observed using the test at the final study visit. HIV self-testing with a blood-based assay was highly acceptable and feasible. HIV self-testing may have the potential to increase testing frequency and to reach high-risk MSM not currently accessing HIV-testing services.

HCV, HBV, and HIV seroprevalence, coinfections, and related behaviors among male injection drug users in Arak, Iran

This study explored the prevalence and related risk behaviors for hepatitis C (HCV), hepatitis B (HBV), and human immunodeficiency virus (HIV) among a sample of male injection drug users (IDUs) in Arak, Iran. One hundred male IDUs attending methadone maintenance clinics between April and September 2012 were enrolled and evaluated for HCV, HBV, and HIV infection. The majority of study participants (56%) had evidence of HCV exposure, 6% had evidence of HBV, and 19% were HIV-infected. Coinfections were frequent; 15% had evidence of HIV and HCV, 6% had evidence of HBV and HCV, and 5% had serologic markers for all three infections. Most (84%) were susceptible to HBV infection. A history of any syringe sharing (54%) and syringe sharing in prison (25%) were common. In bivariate analyses, a history of any syringe sharing and syringe sharing in prison were both associated with all three viral infections. The high prevalence of HCV, HBV, HIV, and coinfections among IDU in Arak is concerning and indicates rapid disease spread outside of Irans main urban centers. Prevention efforts should expand vaccination for IDUs who are nonimmune to HBV and continue to target syringe sharing with efforts such as needle exchange programs, including inside prisons.

Sexual frequency and planning among at-risk men who have sex with men in the United States: implications for event-based intermittent pre-exposure prophylaxis.

Abstract:Intermittent dosing of pre-exposure prophylaxis (iPrEP) has potential to decrease costs, improve adherence, and minimize toxicity. Practical event-based dosing of iPrEP requires men who have sex with men (MSM) to be sexually active on fewer than 3 days each week and plan for sexual activity. MSM who may be most suitable for event-based dosing were older, more educated, more frequently used sexual networking websites, and more often reported that their last sexual encounter was not with a committed partner. A substantial proportion of these MSM endorse high-risk sexual activity, and event-based iPrEP may best target this population.

Antiretroviral drug resistance among antiretroviral‐naïve and treatment experienced patients infected with HIV in Iran

Resistance to antiretroviral therapy (ART) threatens the success of programs to reduce HIV morbidity and mortality, particularly in countries with few treatment options. In the present study, genotype and phenotype data from ART‐naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High‐level resistance to efavirenz (EFV) was more common among participants on EFV‐based regimens than high‐level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r‐based regimens (55.3% vs. 6.7%, P < 0.0001). Two (6.7%) antiretroviral‐naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed. J. Med. Virol. 86:1093–1098, 2014.

Risk Perception, Sexual Behaviors, and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) taken as pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk of HIV infection, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20–35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants’ risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient subcategories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

The HVTN503/Phambili HIV vaccine trial: a comparison of younger and older participants.

By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January–September 2007. Motivations for trial enrolment, social harms, adverse events and loss to follow-up were compared between younger (18–20 years old) and older participants (21–35 years old). Both younger (n = 238) and older participants (n = 563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p = 0.005), while younger males were more likely to enrol because the vaccine may provide protection from HIV-acquisition (p < 0.001). There were no significant differences in the number of social harms reported. Compared to males over 20 years old, 18–20-year-old females were less likely to experience adverse events (OR = 0.1, CI 0.01–0.80) and no more likely to be lost to follow-up (OR = 0.7, CI 0.39–1.25), while 18–20-year-old males were no more likely to experience adverse events (OR = 1.3, CI 0.58–2.83) or loss to follow-up (OR = 0.8, CI 0.51–1.41). Our data support the inclusion of younger participants who are at risk for HIV in future HIV vaccine efficacy trials.