Sybil Hosek

Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: a cohort study

BACKGROUND The effect of HIV pre-exposure prophylaxis (PrEP) depends on uptake, adherence, and sexual practices. We aimed to assess these factors in a cohort of HIV-negative people at risk of infection. METHODS In our cohort study, men and transgender women who have sex with men previously enrolled in PrEP trials (ATN 082, iPrEx, and US Safety Study) were enrolled in a 72 week open-label extension. We measured drug concentrations in plasma and dried blood spots in seroconverters and a random sample of seronegative participants. We assessed PrEP uptake, adherence, sexual practices, and HIV incidence. Statistical methods included Poisson models, comparison of proportions, and generalised estimating equations. FINDINGS We enrolled 1603 HIV-negative people, of whom 1225 (76%) received PrEP. Uptake was higher among those reporting condomless receptive anal intercourse (416/519 [81%] vs 809/1084 [75%], p=0·003) and having serological evidence of herpes (612/791 [77%] vs 613/812 [75%] p=0·03). Of those receiving PrEP, HIV incidence was 1·8 infections per 100 person-years, compared with 2·6 infections per 100 person-years in those who concurrently did not choose PrEP (HR 0·51, 95% CI 0·26-1·01, adjusted for sexual behaviours), and 3·9 infections per 100 person-years in the placebo group of the previous randomised phase (HR 0·49, 95% CI 0·31-0·77). Among those receiving PrEP, HIV incidence was 4·7 infections per 100 person-years if drug was not detected in dried blood spots, 2·3 infections per 100 person-years if drug concentrations suggested use of fewer than two tablets per week, 0·6 per 100 person-years for use of two to three tablets per week, and 0·0 per 100 person-years for use of four or more tablets per week (p<0·0001). PrEP drug concentrations were higher among people of older age, with more schooling, who reported non-condom receptive anal intercourse, who had more sexual partners, and who had a history of syphilis or herpes. INTERPRETATION PrEP uptake was high when made available free of charge by experienced providers. The effect of PrEP is increased by greater uptake and adherence during periods of higher risk. Drug concentrations in dried blood spots are strongly correlated with protective benefit. FUNDING US National Institutes of Health.

The acceptability and feasibility of an HIV preexposure prophylaxis (PrEP) trial with young men who have sex with men.

Background:This study examined the feasibility of a combination prevention intervention for young men who have sex with men (YMSM), an anticipated target population for HIV preexposure prophylaxis (PrEP). Methods:Project PrEPare, a pilot study using a randomized 3-arm design, compared an efficacious behavioral HIV prevention intervention (Many Men, Many Voices—3 MV) alone, 3 MV combined with PrEP (tenofovir/emtricitabine), and 3 MV combined with placebo. Eligible participants were 18- to 22-year-old HIV-uninfected men who reported unprotected anal intercourse in the past year. Participants were screened for preliminary eligibility at youth venues and community organizations and were also referred through social networks. Laboratory screening determined final eligibility. Behavioral and biomedical data were collected at baseline and every 4 weeks thereafter for 24 weeks. Results:Sixty-eight youth (mean age = 19.97 years; 53% African American, 40% Latino) were enrolled; 58 were randomized. Self-reported medication adherence averaged 62% (range, 43%–83%), whereas rates of detectable tenofovir in plasma of participants in the emtricitabine/tenofovir disoproxil fumarate arm ranged from 63.2% (week 4) to 20% (week 24). There were 5 ≥ grade 2 adverse events possibly/probably related to the study medication. Sexual risk behavior declined from baseline to week 24 in all study arms. Conclusions:The feasibility of enrolling at-risk youth, particularly young men who have sex with men of color, into Project PrEPare has been demonstrated. The acceptability of the group intervention along with counseling and testing was high. Self-reported medication adherence and corresponding plasma drug concentrations were low indicating the need for enhanced adherence counseling. Exploration of PrEP use among youth in nonrandomized open label trials is warranted.

The impact of stigma on medication adherence among HIV-positive adolescent and young adult females and the moderating effects of coping and satisfaction with health care

To explore whether HIV stigma negatively impacts adherence to antiviral medications in HIV-infected adolescent women, moderational analysis was conducted and factors identified that could alter said relationship. Study participants were 178 adolescent females age 15-24, enrolled between 2003-2005, from 5 different cities and 60 provided adherence information. Findings reported by this cohort of 60 adolescent women included: medication adherence, 64.3% reporting adherence at baseline and 45.0% at 12 months; HIV stigma score of 57.60 (standard deviation [SD], 11.83; range, 25-86). HIV stigma was not found to be a significant predictor when binary logit regression was run with medication adherence at 1 year. Using moderational analysis, factors that could moderate stigmas effect on medication adherence was still pursued and identified the following to be significant at 12 months: health care satisfaction (B = -0.020, standard error [SE] = 0.010, p < .05); and Coping (proactive coping strategies [B = 0.012, SE = 0.005, p < .05]; turning to family [B = 0.012, SE = 0.016, p < 0.05]; spiritual coping [B = 0.021, SE = 0.010, p < 0.05]; professional help [B = 0.021, SE = 0.010, p < 0.05]; physical diversions [B = 0.016, SE = 0.007, p < 0.05]). Factors that had no significant moderating effects included: social support measures (mean = 74.9; median = 74.0) and depression score greater than 16 = 43%. We conclude that HIV-infected adolescent women experience HIV stigma and poor adherence over time. Factors like health care satisfaction and coping may minimize stigmas effect on medication adherence. Our findings are tempered by a small sample size and lack of a direct relationship between stigma and adherence on binary logit regression analysis.

An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM

Background: Young men who have sex with men (YMSM) are a key population for implementation of preexposure prophylaxis (PrEP) interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 US cities. Methods: Eligible participants were 18- to 22-year-old HIV-uninfected MSM who reported HIV transmission risk behavior in the previous 6 months. Participants were provided daily tenofovir disoproxil fumarate/emtricitabine (Truvada). Study visits occurred at baseline, monthly through week 12, and then quarterly through week 48. Dried blood spots were serially collected for the quantification of tenofovir diphosphate (TFV-DP). Results: Between March and September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age = 20.2; 54.5% black, 26.5% Latino). Diagnosis of sexually transmitted infections, including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with ≥4 pills per week. By week 48, 34% of participants had TFV-DP levels consistent with ≥4 pills per week, with a noticeable drop-off occurring at week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Condomless sex was reported by >80% of participants, and condomless anal sex with last partner was associated with higher TFV-DP levels. Conclusions: Acceptability of PrEP was high, and most participants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the United States may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

Screening and assessing violence and mental health disorders in a cohort of inner city HIV-positive youth between 1998-2006.

The focus of the primary care appointments for HIV-positive youth is often solely on medical concerns. However, these youth also present with mental health issues and histories of exposure to violence. To screen and assess for mental health disorders, HIV-positive youth between the ages of 13 to 24 consecutively enrolled in an adolescent and young adult HIV clinic between 1998-2006 (n = 174), were screened for mental health disorders and violence, using the Client Diagnostic Questionnaire (CDQ). All youth subsequently had diagnostic interviews conducted by psychologists. Findings of the CDQ and the psychological interviews revealed the following. Violence reported by youth occurred in several forms: physical assault/abuse (24% in childhood; 19% as adolescents), sexual abuse/assault (28% in childhood; 15% as adolescents), dating violence (i.e., physical abuse by sexual partner) (18%), and family violence (44%). Females had higher sexual abuse (p < .001). Psychological disorders included: major depressive disorders (15%), generalized anxiety disorder (17%); posttraumatic stress disorder (28%); alcohol abuse disorder (19%); and substance abuse disorder (31%). Physically abused youth had higher symptoms of anxiety (p < 0.05, and PTSD (p < 0.01). Sexually abused youth had higher symptoms of PTSD (p < 0.05). Youth with family violence had higher symptoms of Anxiety Disorder (p < 0.05) and PTSD (p < 0.01). CDQ findings closely correlated with diagnostic assessments of the psychological interview. We conclude that inner city HIV-positive youth present with high prevalence of violence and with psychological disorders. Failure to screen for and treat these psychological disorders may impact successful treatment of their HIV infection.

Preventing HIV among young people: research priorities for the future.

Objective:To review the current state of knowledge on the prevention of sexual transmission of HIV in adolescents and to highlight the existing gaps and priority areas for future research. Background:A disproportionate burden of HIV infections falls on adolescents, a developmental stage marked by unique neural, biological, and social transition. Successful interventions are critical to prevent the spread of HIV in this vulnerable population. Methods:We summarized the current state of research on HIV prevention in adolescents by providing examples of successful interventions and best practices, and highlighting current research gaps. Results:Adolescent interventions fall into 3 main categories: biomedical, behavioral, and structural. The majority of current research has focused on individual behavior change, whereas promising biomedical and structural interventions have been largely understudied in adolescents. Combination prevention interventions may be particularly valuable to this group. Conclusions:Adolescents have unique needs with respect to HIV prevention, and, thus, interventions should be designed to most effectively reach out to this population with information and services that will be relevant to them.

Antiretroviral pre-exposure prophylaxis implementation in the United States: a work in progress

After the initial approval of the use of tenofovir disoproxil fumarate‐emtricitabine (TDF/FTC) by the US Food and Drug Administration in 2012 for anti‐HIV pre‐exposure prophylaxis (PrEP), uptake was initially limited, but more recent community surveys and expert opinion suggest wider acceptance in some key populations.

Building our youth for the future

Adolescents and young adults are at increased risk for HIV due to the many developmental, psychological, social, and structural transitions that converge in this period of the lifespan. In addition, adolescent deaths resulting from HIV continue to rise despite declines in other age groups. There are also young key populations (YKPs) that bear disproportionate burdens of HIV and are the most vulnerable, including young men who have sex with men (MSM), transgender youth, young people who inject drugs, and adolescent and young adult sex workers. As a society, we must do more to stop new HIV infections and untimely HIV‐related deaths through both primary and secondary prevention and better management approaches. Using an interwoven prevention and treatment cascade approach, the starting point for all interventions must be HIV counselling and testing. Subsequent interventions for both HIV‐negative and HIV‐positive youth must be “adolescent‐centred,” occur within the socio‐ecological context of young people and take advantage of the innovations and technologies that youth have easily incorporated into their daily lives. In order to achieve the global goals of zero infections, zero discrimination and zero deaths, a sustained focus on HIV research, policy and advocacy for YKPs must occur.

Stressors and Sources of Support: The Perceptions and Experiences of Newly Diagnosed Latino Youth Living with HIV

Little is known of the experience of Latino youth with HIV infection in the United States, especially with respect to stressors and how these youth cope with said stressors. This study reports on a subset (Latino/Hispanic self-identified youth, n=14) of qualitatively interviewed youth (n=30), both in individual interviews and in focus group discussion settings, aware of their HIV diagnosis for 12-24 months (mean: 16.7 months; standard deviation [SD], 4.89) Youth were 16-24 years old (M=21.5 years), female (43%) and males (57%). Youth were recruited from three cities: Chicago, New York, and San Juan (Puerto Rico). Interviews of Latinos (n=14) were reviewed for sources of stressors and support. Seven themes emerged in analyzing stated sources of stressors: (1) initial psychosocial responses to HIV diagnosis, (2) disclosure to family and friends, (3) stigma related to receiving an HIV diagnosis, (4) body image and concerns of the physical changes associated with HIV and antiretroviral medications, (5) taking antiretroviral medications and side effects, (6) the disruption of their future life goals, and (7) reproductive health concerns. Identified sources of support and coping were described including; gaining appreciation for what matters in life, adapting and developing achievable goals, reordering priorities and relying on religion and spiritual beliefs for health outcomes. The information gathered is from individual interviews and from focus group discussions can be used to increase the understanding of this understudied population while improving services to engage and retain these youth in care.

Behavioral considerations for engaging youth in HIV clinical research.

From both scientific and ethical perspectives, it is important that youth be enrolled in biomedical HIV prevention clinical trials. At the same time, adolescents, as minors, are considered a vulnerable population requiring particular attention to the reduction of potential harm associated with participation in such trials. In this article, we review the evidence supporting enrollment of youth in HIV clinical trials, including data on HIV infection rates, sexual behavior, and cognitive, psychosocial, and neurophysiological development. Next, we address the potential risks associated with clinical trial participation, with a focus on the concept of preventive misconception, the tendencies to (1) overestimate the probability of assignment to the experimental condition, as opposed to the placebo, and (2) assume that the experimental intervention is efficacious. Finally, we discuss targeted interventions to reduce preventive misconception and the importance of developing and testing adolescent-friendly risk-reduction interventions that are tailored to the structure and time frame of a biomedical HIV prevention clinical trial. The very issues that make inclusion of youth in HIV prevention clinical trials necessary also demand that particularly intensive efforts be made to protect participating minors from the harm that could accrue from a clinical trial.