State of The Science of Adherence in Pre-Exposure Prophylaxis and Microbicide Trials

Muchomba, Felix M.; Gearing, Robin E.; Simoni, Jane M.; El‐Bassel, Nabila

doi:10.1097/qai.0b013e31826f9962

Cited by 49 publications

(38 citation statements)

References 45 publications

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“…13 The analysis of pharmacologic levels of antiretroviral drugs has emerged as an objective measure of study product use in PrEP trials 1–4 and may help identify groups at risk for non-adherence, who may benefit from adherence support, and help identify those most likely to adhere to the PrEP regimen.…”

Section: Introductionmentioning

confidence: 99%

Patterns and Correlates of PrEP Drug Detection Among MSM and Transgender Women in the Global iPrEx Study

Liu

Glidden

Anderson

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Adherence to pre-exposure prophylaxis (PrEP) is critical for efficacy. Antiretroviral concentrations are an objective measure of PrEP use and correlate with efficacy. Understanding patterns and correlates of drug detection can identify populations at risk for non-adherence and inform design of PrEP adherence interventions. Methods Blood antiretroviral concentrations were assessed among active-arm participants in iPrEx, a randomized, placebo-controlled trial of emtricitabine/tenofovir in men who have sex with men (MSM) and transgender women in 6 countries. We evaluated rates and correlates of drug detection among a random sample of 470 participants at week 8 and a longitudinal cohort of 303 participants through 72 weeks of follow-up. Results Overall, 55% (95% CI 49–60%) of participants tested at week 8 had drug detected. Drug detection was associated with older age and varied by study site. In longitudinal analysis, 31% never had drug detected, 30% always had drug detected, and 39% had an inconsistent pattern. Overall detection rates declined over time. Drug detection at some or all visits was associated with older age; indices of sexual risk, including condomless receptive anal sex; and responding "don't know" to a question about belief of PrEP efficacy (0–10 scale). Conclusions Distinct patterns of study-product use were identified, with a significant proportion demonstrating no drug detection at any visit. Research literacy may explain greater drug detection among populations having greater research experience, such as older MSM in the US. Greater drug detection among those reporting highest-risk sexual practices is expected to increase the impact and cost-effectiveness of PrEP.

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Section: Introductionmentioning

confidence: 99%

Patterns and Correlates of PrEP Drug Detection Among MSM and Transgender Women in the Global iPrEx Study

Liu

Glidden

Anderson

et al. 2014

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…However, the similarity of many of these findings to factors influencing adherence to other treatment and prevention regimens suggest their relevance. [21][22][23][24][25][26][27]52 We combined data from FG with those from IDI; combining these units of analysis may have resulted in both over-and underreporting of qualitative themes, as well as an increase in socially desirable responses. Finally, only a proportion of study volunteers in SF were interviewed, who may not be representative of the entire cohort.…”

Section: Limitationsmentioning

confidence: 99%

“…I would put it in the little pill box and put it in my book bag and sometimes I'd forget..I have some friends who's HIV positive that take 4 or 5 pills a day.so I asked them how they managed and they gave me tips on taking medication.I brush my teeth every morning, so I take mines before I brush my teeth, that way I know I took 'em. (Interview participant 6, age 41, African American, visit week 52) A few participants reported some initial discomfort disclosing missed pills to staff in the first few months of participation. These discussions included mention of coming to realize that missed pills would not affect their participation and with positive rapport with staff, concerns with disclosing episodic missed pills were alleviated.…”

mentioning

confidence: 99%

Participant Experiences and Facilitators and Barriers to Pill Use Among Men Who Have Sex with Men in the iPrEx Pre-Exposure Prophylaxis Trial in San Francisco

Gilmore

Liu

Koester

et al. 2013

AIDS Patient Care and STDs

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In 2010, the iPrEx study demonstrated efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) in reducing HIV acquisition among men who have sex with men. Adherence to study product was critical for PrEP efficacy, and varied considerably, with FTC/TDF detection rates highest in the United States. We conducted a qualitative study to gain insights into the experiences of iPrEx participants in San Francisco (SF) where there was high confirmed adherence, to understand individual and contextual factors influencing study product use in this community. In 2009 and 2011, we conducted focus groups and in-depth interviews in 36 and 16 SF iPrEx participants, respectively. Qualitative analyses indicate that participants joined the study out of altruism. They had a clear understanding of study product use, and pill taking was facilitated by establishing or building on an existing routine. Participants valued healthcare provided by the study and relationships with staff, whom they perceived as nonjudgmental, and found client-centered counseling to be an important part of the PrEP package. This facilitated pill taking and accurate reporting of missed doses. Adherence barriers included changes in routine, side effects/intercurrent illnesses, and stress. Future PrEP adherence interventions should leverage existing routines and establish client-centered relationships/ environments to support pill taking and promote accurate reporting.

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“…Adherence to frequent dosing is burdensome to the user and has emerged as a key factor in explaining the heterogeneous efficacy outcomes of HIV-1 preexposure prophylaxis (PrEP) clinical trials (4)(5)(6)(7). It is well established across different delivery methods that adherence to therapy is inversely related with the dosing period (8)(9)(10)(11).…”

mentioning

confidence: 99%

Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

Gunawardana

Remedios-Chan

Miller

et al. 2015

Antimicrob Agents Chemother

150

196

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e Oral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention. Adherence to the dosing regimen has emerged as a critical factor determining efficacy outcomes of clinical trials. Because adherence to therapy is inversely related to the dosing period, sustained release or long-acting ARV formulations hold significant promise for increasing the effectiveness of HIV-1 preexposure prophylaxis (PrEP) by reducing dosing frequency. A novel, subdermal implant delivering the potent prodrug tenofovir alafenamide (TAF) with controlled, sustained, zero-order (linear) release characteristics is described. A candidate device delivering TAF at 0.92 mg day ؊1 in vitro was evaluated in beagle dogs over 40 days for pharmacokinetics and preliminary safety. No adverse events related to treatment with the test article were noted during the course of the study, and no significant, unusual abnormalities were observed. The implant maintained a low systemic exposure to TAF (median, 0.85 ng ml ؊1 ; interquartile range [IQR], 0.60 to 1.50 ng ml ؊1 ) and tenofovir (TFV; median, 15.0 ng ml ؊1 ; IQR, 8.8 to 23.3 ng ml ؊1 ), the product of in vivo TAF hydrolysis. High concentrations (median, 512 fmol/10 6 cells over the first 35 days) of the pharmacologically active metabolite, TFV diphosphate, were observed in peripheral blood mononuclear cells at levels over 30 times higher than those associated with HIV-1 PrEP efficacy in humans. Our report on the first sustained-release nucleoside reverse transcriptase inhibitor (NRTI) for systemic delivery demonstrates a successful proof of principle and holds significant promise as a candidate for HIV-1 prophylaxis in vulnerable populations. O ral or topical daily administration of antiretroviral (ARV) drugs to HIV-1-negative individuals in vulnerable populations is a promising strategy for HIV-1 prevention, but clinical outcomes have varied widely (1-3). Adherence to frequent dosing is burdensome to the user and has emerged as a key factor in explaining the heterogeneous efficacy outcomes of HIV-1 preexposure prophylaxis (PrEP) clinical trials (4-7). It is well established across different delivery methods that adherence to therapy is inversely related with the dosing period (8-11). Sustained-release or long-acting ARV formulations hold significant promise as a means of reducing dosing frequency, thereby increasing the effectiveness of HIV-1 PrEP.Long-acting preexposure prophylaxis (LA-PrEP) is an alternative regimen to daily dosing designed to mitigate the abovedescribed adherence challenges (12, 13). LA-PrEP has been based primarily on ARV nanoparticles for parenteral administration as injections (12,14). Dosing intervals of 1 month or longer for injectable, long-acting, nanomilled formulations of the integrase strand-transfer inhibitor cabotegravir (GSK1265744) and the nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine are undergoing clinical evaluation as possible regimens for H...

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State of The Science of Adherence in Pre-Exposure Prophylaxis and Microbicide Trials

Cited by 49 publications

References 45 publications

Patterns and Correlates of PrEP Drug Detection Among MSM and Transgender Women in the Global iPrEx Study

Patterns and Correlates of PrEP Drug Detection Among MSM and Transgender Women in the Global iPrEx Study

Participant Experiences and Facilitators and Barriers to Pill Use Among Men Who Have Sex with Men in the iPrEx Pre-Exposure Prophylaxis Trial in San Francisco

Pharmacokinetics of Long-Acting Tenofovir Alafenamide (GS-7340) Subdermal Implant for HIV Prophylaxis

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