Yearly Archives: 2018

Presented at HIVR4P 2018 – (OA15.05) Cabotegravir (CAB) Long-acting (LA) Phase 3 (Ph3) PrEP Dose Selection Based on Population Pharmacokinetics (PPK) in Healthy and HIV-infected Adults

Kelong Han, Parul Patel, Mark Baker, David Margolis, William Spreen, Alex Rinehart, RaphaelLandovitz, Susan Ford

Background: Cabotegravir is an integrase inhibitor currently in Ph3 development as an oral tablet and an IM LA injection for HIV treatment and prevention. CAB LA is effective in preventing SHIV infection in macaques at clinically relevant concentrations. A CAB PPK model including intrinsic and extrinsic factors was developed with data from Phase 1/2 studies and simulations were performed to inform PrEP Ph3 dosing strategies.

Methods: Analyses were implemented in NONMEM 7.3 and R. 12,294 CAB plasma concentrations following oral doses from 5-60mg and LA doses from 100-800mg obtained from 881 healthy (44%) and HIV infected (56%) adults in 11 studies were included in the model. Intramuscular (IM) CAB LA was administered in 64% of subjects. Covariates were evaluated using forward addition and backward elimination. Bootstrapping and visual predictive checks were used to assess model adequacy. Simulations were performed using final parameter estimates to deliver a LA profile that achieves concentrations protective against infection in preclinical species.

Results: A two-compartment model with first-order oral and IM absorption and elimination described the data well. Clearances and volumes were scaled to body size. CAB LA absorption rate constant was lower in females, in subjects with higher BMI and for unsplit (vs. divided dose) injections; however, each covariate alone was associated with < 15% change in steady-state exposure. CAB LA 600mg (3mL unsplit) IM on Day 1, W4 and Q8W was selected for Ph3 PrEP studies in males and females to achieve steady-state concentrations throughout the dosing interval above a threshold where CAB LA has demonstrated preclinical efficacy. Simulations were also performed to inform protocol management of delayed or missed doses.

Conclusions: A robust CAB PPK model including covariates yielded selection of an every 8-week injectable regimen of CAB LA regimen for Ph3 PrEP studies in high-risk males and females. Management of dosing delays is informed by model based simulations.

Presented at HIVR4P 2018 – (P05.06) Sexual Risk and Study Drug Detection in MSM Participants in a Phase II Study of Maraviroc (MVC) +/- Tenofovir DF (TDF) or FTC versus TDF/FTC for PrEP

Kenneth Mayer, Krista Yuhas, K. Rivet Amico, Timothy Wilkin, Raphael Landovitz, Paul Richardson, Mark Marzinke, Craig Hendrix, Susan Eshleman, Leslie Cottle, Adriana Andrade, Karen Klingman, Wairimu Chege, Alex Rinehart, James Rooney, Phillip Andrew, Ying Chen, Marybeth McCauley, Roy Gulick, HPTN 069/ACTG 5305 Study Group

Background: PrEP effectiveness depends on medication adherence while engaging in HIV risk behavior. We evaluated antiretroviral (ARV) plasma concentrations in relation to reported sexual risk behavior in a study of MVC +/- TDF or FTC versus TDF/FTC for PrEP in at-risk MSM and cis- or transgender women (HPTN 069/ACTG 5305).

Methods: The current analysis included data from 226 participants (pts) who were male at birth for whom computer-assisted self-interview behavioral data and plasma ARV drug assays were available at 24 and/or 48 week visits. Poisson generalized estimating equations (GEE) regression were used to test for associations between sexual risk, sociodemographic and behavioral variables, and study drug detection. Covariates associated with the outcome at p< 0.10 in bivariate analyses were included in a multivariable model

Results: The median (IQR) age was 30 (25, 37) years old; 98% identified as MSM. Almost half (48.2%) had completed college; 27.4% were Black and 21.7% Latino. At weeks 24 and 48, equal proportions of pts reported condomless anal sex (CAS) in the prior month with 0, 1 or >1 partners. The prevalence of CAS was similar at 24 and 48 weeks. Study ARV’s were detected in the plasma of 69% of those who reported no CAS at week 24 or 48, compared to 92% who reported CAS with 1 partner and 92% of those who reported CAS with >1 partner during the same time period. GEE models found that CAS was associated with detectable ARV drug concentrations (p value < 0.001). Individuals with greater education were more likely to have detectable plasma ARV drugs (p value = 0.005), while age, race or ethnicity were not associated with ARV drug detection.

Conclusions: In a study in which all participants received at least one ARV for PrEP, pts who reported condomless anal sex and/or advanced education had higher rates of ARV drug detection. Findings suggest that CAS, education and PrEP adherence are related; thus, engaging PrEP users in understanding their HIV risks may facilitate prevention effective PrEP use.

Presented at HIVR4P 2018 – (P14.01) Online Survey about Reasons for Stopping PrEP is an Opportunity to Re-engage Inactive PrEP Clients

Chelsea Shover, David Flores, Matthew Beymer, Michelle DeVost, Pamina Gorbach, Risa Flynn, K. Rivet Amico, Paul Chavez, Phoebe Lyman, Brian Toynes, Robert Bolan

Background: Studies of HIV pre-exposure prophylaxis (PrEP) in community settings reveal continuation challenges. We examined the contribution of health services barriers, medication factors, transitions between healthcare providers, and changes in sexual risk to PrEP discontinuation among patients who initiated PrEP at a large community clinic in Los Angeles, CA.

Methods: From Feb 2018 – Apr 2018, 810 patients who initiated PrEP at the Los Angeles LGBT Center between Jan 2016 and Sept 2017 with current gaps in PrEP care (>120 days from last PrEP visit) were invited to ake an online survey which assessed current PrEP use and reasons for stopping PrEP or missing doses. During that period, 2,418 patients had been prescribed PrEP.

Results: Of 168 patients who took the survey, 49% (n=83) had stopped taking PrEP, 43% (n=72) had taken PrEP within the past seven days (31 had transitioned to a different provider), 6% (n=10) reported they had never taken PrEP, and 3 did not report when they last took PrEP. Of those not currently taking PrEP (n=93), 74% (n=69) provided reasons for stopping PrEP or missing doses. Most common reasons were entering a monogamous relationship (43%), cost (38%), side effects (38%), insurance problem (36%), “I did not think I needed to take PrEP” (33%), forgetting (29%), problem filling prescription (28%), not having anal sex (28%). At the end of the survey, 23 (25%) of those who discontinued asked to be called to schedule another PrEP appointment. By mid-April, 5 (22%) had attended appointments and been prescribed PrEP again. One patient who became HIV positive after discontinuing PrEP was linked to HIV care.

Conclusions: The survey enabled us to re-engage patients who still wanted PrEP. Lowering health services barriers and providing ongoing PrEP education may improve continuation. By developing personal PrEP action plans, providers can support patients in managing their engagement in PrEP through seasons of risk if they do not intend to be on PrEP long-term or indefinitely.

Presented at HIVR4P 2018 – (P03.15) Intimate Partner Violence and Engagement in the HIV Care Continuum Among Women in sub-Saharan Africa: A Prospective Cohort Study

Sarah T. Roberts, Ariane van der Straten, Christine Tagliaferri Rael, Pamina M. Gorbach, Lameck Chinula, Thesla Palanee-Phillips, Kalendri Naidoo, Zakir Gafoor, Bonus Makanani, Mobolaji Ibitoye, Jennifer E. Balkus, Sharon A. Riddler

Background: Intimate partner violence (IPV) is associated with poor engagement in HIV care and treatment. However, most studies have been cross-sectional and conducted in North America. We examined the association between physical IPV and HIV care outcomes in a prospective cohort study of women living with HIV in sub-Saharan Africa.

Methods: MTN-015 enrolled women aged 18-42 years in Malawi, South Africa, Uganda, and Zimbabwe who acquired HIV-1 infection during the MTN-003 and MTN-020 clinical trials of microbicides for HIV prevention. Experience of physical IPV in the past year was self-reported at enrollment. Outcomes were time to first engagement in HIV care, ART initiation within 6 months of eligibility, and viral load suppression (HIV RNA < 200 copies/ml) after 6 months on ART. We used multivariable Cox proportional hazards and Poisson regression models to test associations between IPV and each outcome.

Results: A total of 351 participants were enrolled from 2010-2015. Median age was 24 years and 86% were in South Africa. Fifty-one participants (15%) reported physical IPV at enrollment. Among 232 women not engaged in care at enrollment, median time to first engagement in care was 1.6 years, with no difference by IPV status. Among 175 women who became eligible for ART, 60% initiated within 6 months, and women reporting physical IPV were less likely to initiate ART (adjusted RR 0.74, 95% CI 0.53-1.03, p=0.08). Of 360 visits occurring after 6 months on ART among 129 women, 74% had viral suppression, with no differences by IPV status.

Conclusions: Among newly diagnosed HIV-infected women in sub-Saharan Africa, physical IPV was not significantly associated with engagement in the HIV care continuum, though a trend for delayed ART initiation was observed. A more detailed and repeated measure of IPV may improve our understanding of how IPV impacts the health of women living with HIV by identifying additional women who have experienced emotional, sexual, or economic IPV or experienced physical IPV after enrollment.

Presented at HIVR4P 2018 – (Po3.54) Never Have I Ever: Factors Associated With Never Testing for HIV and With Testing Positive for HIV at First HIV Test in Peruvian MSM and TW

Susan Chavez-Gomez, R. Colby Passaro, Eddy R. Segura, Williams Gonzales-Saavedra, Angelica Castañeda-Huaripata, Eduardo Cachay, Renato Bobadilla, Steven Shoptaw, James Dilley, Jesse L. Clark, Robinson Cabello

Background: To understand why high-risk men who have sex with men (MSM) and transgender women (TW) do not access prevention services, we examined correlates of never testing for HIV and factors associated with testing positive at first HIV test among Peruvian MSM and TW.

Methods: During a 2017 study of rectal STI screening and HIV prevention, MSM/TW reporting condomless receptive anal intercourse (cRAI) completed a survey of demographic and social network characteristics and sexual risk behavior, and were tested for rectal gonorrhea (GC), chlamydia (CT), syphilis, and HIV. Separate Poisson regression analyses for MSM and TW estimated: i) Correlates of never having tested for HIV; ii) Correlates of testing positive with no history of HIV testing.

Results: Of 588 participants, 21.7% (101/464) of MSM and 18.5% (23/124) of TW denied prior HIV testing. MSM “Never Testers” were more likely than “Prior Testers” to be younger (aPR, 95% CI: 0.94, 0.01-0.97), to report a pasivo (receptive; 1.66, 1.18-2.34) or activo (insertive; 2.27, 1.10-4.72) sexual role, and to test positive for HIV (1.64, 1.17-2.29). HIV prevalence in Never Testers was 32.7% versus 18.8% in Prior Testers (p< 0.01). Rectal GC (2.41, 1.45-4.00) was associated with HIV infection in MSM Never Testers. TW Never Testers were more likely to report < 15 gay contacts in their social network (3.77, 1.38-10.28), and to test positive for HIV (2.53, 1.00-6.39) than Prior Testers. Only 8.1% of MSM and TW Never Testers had heard of PrEP compared to 27.4% of Prior Testers (p< 0.01). MSM and TW Never Testers reported similar barriers to testing: Fear of test results (45.2%), No access to testing services (32.3%).

Conclusions: We observed a high prevalence of HIV among MSM and TW with no history of HIV testing. Innovative strategies to encourage young people to test regularly, like incorporating rectal STI screening into HIV prevention services, are needed to identify the MSM and TW who would benefit most from biomedical prevention services like PrEP and TasP.

Presented at HIVR4P 2018 – (P28.08) Providing PrEP Navigation to High-risk Populations With Multiple Health Disparities in Los Angeles, CA, USA: A Comparison of MSM and Trans Women

Cathy Reback, Dennis Rünger, Jesse Fletcher

Background: Men who have sex with men (MSM) and trans women are the two groups at highest risk of HIV infection in the US. The majority of new HIV diagnoses each year in the US occur among MSM, and national HIV prevalence among trans women is estimated to be 18-25%, the highest of any risk category or demographic group. For both MSM and trans women, risk of seroconversion is further elevated among racial/ethnic minority members.

Methods: From 12/2016 to 3/2018, HIV-negative MSM (n=129) and trans women (n=58) enrolled in a PrEP navigation service program in Los Angeles, California, designed to link participants into PrEP medical services. Assessments occurred at baseline and 90-days post-baseline.

Results: MSM were older than trans women (43.3 vs. 34.9 yrs, p< .001). Most participants identified as African-American (MSM=53%, trans women=45%), followed by Caucasian for MSM (24%) and Hispanic/Latin for trans women (28%). There were no significant differences in education, employment, or housing instability. MSM participants were more likely to report drug use (81% vs. 64%, p=.009) and condomless anal sex (81% vs. 62%, p=.011); trans women were more likely to report exchange sex (51% vs. 19%, p< .001). Most participants successfully linked to PrEP (MSM: 92%, trans women: 90%, ns), but MSM evidenced fewer median days to linkage (9 vs. 13.5, p< .001). At 90-day follow-up for those who initiated PrEP (MSM, n=88; trans women, n=32), 66% of MSM and 75% of trans women were still taking PrEP (ns). Of those, similar proportions of MSM and trans women reported no days with a missed dose in the past 4 days (88% vs. 79%), past 30 days (59% vs. 46%), and past 90 days (43% vs. 29%, all ns.)

Conclusions: PrEP linkage was delayed for trans women, compared to MSM. Though both groups evidenced high PrEP uptake (approx. 90%) and comparable adherence rates, preliminary results indicate that ongoing services are needed to increase adherence rates.