[Show abstract][Hide abstract] ABSTRACT: A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a “relaxed” definition (accounting for off-prescription dosing) and 40 % per a “strict” definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.
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Full-text · Article · Nov 2014 · AIDS and Behavior
[Show abstract][Hide abstract] ABSTRACT: Background: Biological or behavioral factors may impact vaccine immunogenicity and efficacy. We investigated the relationship between trial volunteer baseline demographic and behavioral factors and vaccine-specific immune responses in 3 phase I HIV vaccine clinical trials.
Methods: Volunteers at low-risk for HIV infection received 2-4 injections of candidate HIV vaccines over 3 to 6 months in 3 phase I HIV vaccine clinical trials in Kenya, Uganda, Rwanda, Zambia, South Africa and the US from 2010–2013. Vaccine recipients in trial arms with robust IFN-g ELISPOT responses at 4 weeks after the last vaccination were included in the analysis. Multivariate logistic regression model with backward selection was used to assess the relationship between parameters at baseline (gender, age, body mass index (BMI), alcohol use, drug use) and the odds of a positive IFN-g ELISPOT, defined as>38 spot forming cells/ml and>4 fold mean background.
Results: 284 volunteers receiving at least one vaccine dose were included in the analysis. Of these, 44% were female, 54%≤age 26, mean BMI 23.1 (range 14–48). 13% reported weekly or daily alcohol use. Self-reported drug use was rare. Overweight BMI (≥30) correlated with 78% decreased odds of a positive ELISPOT response, p<0.005 When analyzed as a continuous variable, one unit increase in BMI correlated to a 8% decrease in the odds of a positive ELISPOT response, p<0.001. Daily or weekly alcohol use, compared to no alcohol use correlated with 3-fold increase in the odds of positive ELISPOT responses (p<0.05). Age, gender, and any drug use were not associated with ELISPOT responses.
Conclusions: Overweight BMI appears to be associated with decreased immune response to certain HIV vaccine candidates when measured by IFN-g ELISPOT in healthy, HIV low-risk populations. This effect may impact interpretation of phase I trials which typically have small group sizes. The positive association with alcohol use deserves further analysis.
No preview · Article · Oct 2014 · AIDS Research and Human Retroviruses
[Show abstract][Hide abstract] ABSTRACT: Background: Participation in HIV prevention trials may have important positive or negative social impacts for the volunteer. We assessed self-reported social impact in 3 phase 1 HIV vaccine clinical trials in 5 African countries.
Methods: Three phase 1 HIV vaccine clinical trials in Kenya, Uganda, Rwanda, Zambia and South Africa enrolled volunteers at low-risk for HIV, who received 2-4 injections and were followed for up to 16 months with repeated HIV testing and counseling, plus mucosal sampling at the Kenyan sites. At the final study visit, self-reported data on potential social impact of trial participation was collected using a standardized questionnaire. Volunteers rated whether the impact was harmful or not, and graded harmful impacts as mild, moderate, major. Comparisons of categorical factors were conducted using the Fisher's exact test. A two-sided p<0.05 was considered statistically significant.
Results: Social impact data was collected on 383 trial volunteers. 42% (162/383) reported one or more (256 total) social impacts. The majority (175/256, 68%) were reported as positive impacts, with the most common being ‘affecting your feelings on the AIDS epidemic' 58% (101/175), and ‘affecting feelings about yourself' 14% (24/175). The most common negative impacts were ‘affecting health' 33% (27/81) and ‘affecting relationship with friends’ 17% (14/81). Negative social impacts were not more common in women (12%) than men (17%) (p=0.15), but varied by country (Uganda 28%, Kenya 22%, Zambia 8%, Rwanda 6%, South Africa 0%, p<0.0001). A total of 7 negative impacts were rated as major: low libido (4), falling sick frequently (1), believed infected by HIV (1) and dental problems (1); and 24 were rated as moderate.
Conclusions: Trial volunteers reported largely positive social impacts and few major negative impacts after participation in phase 1 HIV vaccine trials. These data will inform appropriate counseling messages in future phase 1 and larger vaccine efficacy trials in Africa.
Preview · Article · Oct 2014 · AIDS Research and Human Retroviruses
[Show abstract][Hide abstract] ABSTRACT: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV acquisition has been evaluated using a daily regimen. However, adherence to long term daily medication is rarely perfect. Intermittent regimen may be a feasible alternative. Preclinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals. However, little is known about intermittent PrEP regimens.
Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Uganda were randomly assigned to receive daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were blinded to drug assignment, but not to regimen assignment.
Volunteers were followed for 4 months after randomization, with monthly clinical and laboratory safety assessments and comprehensive HIV risk reduction services. Adherence was monitored using medication event monitoring system (MEMS) and self-report. Sexual activity data were collected via daily short text message (SMS) and self-report. HIV-specific immune responses were assessed by IFN-γ ELISPOT.
Both daily and intermittent oral TDF/FTC regimens were well tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for post-coital dosing. SMS response rate was 74%, but increased to 80% after excluding server outages; results may have been affected by the novelty of this measure. The majority of volunteers expressed willingness with no particular preference for either regimen.
Both daily and intermittent oral PrEP dosing regimens were safe. Adherence was high for daily and fixed intermittent dosing; post-coital dosing was associated with poor adherence. Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing.
Clinicaltrials.gov number NCT00931346.
[Show abstract][Hide abstract] ABSTRACT: This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.
No preview · Article · Oct 2012 · AIDS and Behavior
[Show abstract][Hide abstract] ABSTRACT: This mixed methods study reports on product acceptance from a Phase I clinical trial of a candidate non-nucleoside reverse transcriptase inhibitor (NNRTI) vaginal microbicide product (UC781). The product was evaluated in the context of a Phase I clinical trial in an area characterized by high HIV prevalence among minority women. The findings will inform the development of an acceptable microbicide that will address the needs of diverse women and their partners.
This is a mixed methods study of 34 racially and ethnically diverse female participants and 10 male partners in Atlanta, Georgia. Chi-square tests for marginal homogeneity and kappa statistics were calculated to analyze differences between groups on product attributes and use intention. ANOVA was used to examine difference between the treatment groups. Qualitative data were analyzed via constant comparative methodology.
Thirty-four out of the original female cohort of 36 completed the questionnaire. Approval of future microbicide development was high at 91.2% (n=31) despite a lack of enthusiasm for the placebo and UC781 formulations. Overall female acceptability was correlated with personal protection motivation (r=1.00, p<0.001). African American women indicated greater likelihood of post-licensure microbicide use (X(2) (3)=7.9, p=0.048) and ascribed greater importance to its potential protection against HIV (X(2) (4)=18.7, p=0.001) and its potential for dual protection (protective against STIs and/or pregnancy) compared to white women (X(2) (4)=11.3, p=0.024). Men and women supported development in the form of an intravaginal ring or suppository. Men were more likely to encourage female adoption of the method if it afforded HIV protection (r=0.935, p=0.001).
Although most women agreed that the development of a microbicide was an important endeavor, quantitative and qualitative data indicated they would not use placebo or UC781 due to the objectionable viscosity, odor, and color. Male partners felt the potential protective benefit of a future microbicide product was its most important feature.
Full-text · Article · Jul 2012 · Journal of AIDS & Clinical Research
[Show abstract][Hide abstract] ABSTRACT: Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW).
MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen.
Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens.