Adherence Support Approaches in Biomedical HIV Prevention Trials: Experiences, Insights and Future Directions from Four Multisite Prevention Trials

Amico, K. Rivet; Mansoor, Leila E.; Corneli, Amy; Torjesen, Kristine; Straten, Ariane van der

doi:10.1007/s10461-013-0429-9

Cited by 122 publications

(104 citation statements)

References 23 publications

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“…7,23,38 An evaluation of interventions to promote adherence to PrEP recommended participant-centered approaches, including addressing the specific context in which an individual incorporates and negotiates PrEP use. 41 While complex, resource-intensive interventions are most effective for improving adherence to medical interventions in general, a systematic review also found evidence to support low-cost, low-intensity interventions that provided education or telephone calls. 38 CDC guidelines recommend that clinicians incorporate motivational interviewing into their visits for prescribing PrEP with 4 simple items: (1) When you have taken medications previously?…”

Section: Supporting Adherence To Prepmentioning

confidence: 99%

Preexposure Prophylaxis (PrEP) for HIV Prevention: The Primary Care Perspective

Conniff

Evensen

2016

The Journal of the American Board of Family Medicine

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Section: Supporting Adherence To Prepmentioning

confidence: 99%

Preexposure Prophylaxis (PrEP) for HIV Prevention: The Primary Care Perspective

Conniff

Evensen

2016

The Journal of the American Board of Family Medicine

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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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“…Multiple HIV PrEP clinical trials have demonstrated that vaginal and oral ARV regimens based on the nucleoside reverse transcriptase inhibitor (NRTI) tenofovir (TFV) can be effective in susceptible men, women, and partners of HIV-infected individuals (3)(4)(5)(6)(7)(8)(9), but other studies based on analogous drug regimens were unsuccessful at reducing the rates of HIV acquisition (10)(11)(12). A critical factor driving success in these trials appears to involve sustaining high adherence to frequent dosing (13).…”

mentioning

confidence: 99%

Combination Pod-Intravaginal Ring Delivers Antiretroviral Agents for HIV Prophylaxis: Pharmacokinetic Evaluation in an Ovine Model

Moss

Butkyavichene

Churchman

et al. 2016

Antimicrob Agents Chemother

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P reexposure prophylaxis (PrEP) using FDA-approved antiretroviral (ARV) drugs holds significant promise as a strategy in the prevention of HIV infection. By analogy to highly active antiretroviral therapy (HAART), a combination of ARV agents likely is essential for optimally effective HIV PrEP (1, 2). Multiple HIV PrEP clinical trials have demonstrated that vaginal and oral ARV regimens based on the nucleoside reverse transcriptase inhibitor (NRTI) tenofovir (TFV) can be effective in susceptible men, women, and partners of HIV-infected individuals (3-9), but other studies based on analogous drug regimens were unsuccessful at reducing the rates of HIV acquisition (10-12). A critical factor driving success in these trials appears to involve sustaining high adherence to frequent dosing (13).Adherence to therapy was found to be inversely related to dosing periods across different delivery methods (14-17). Topical delivery of ARV drugs using intravaginal rings (IVRs) is believed to improve adherence (18) while maintaining sustained mucosal microbicide levels independently of coitus and daily dosing (19). A recent phase 3, randomized, double-blind, placebo-controlled trial involving 2,629 African women evaluating a monthly IVR delivering the nonnucleoside HIV-1 reverse transcriptase inhibitor dapivirine (DPV) showed that this dosing modality can be effective at preventing HIV-1 infection (20). Overall, the incidence of HIV-1 infection in the DPV group was lower by 37% than that in the placebo group, following the exclusion of data from two sites that exhibited lower-than-expected protocol and product adherence. The efficacy of HIV-1 prevention was as high as 61% among women 25 years of age or older. However, the delivery of two or more ARV drugs by the use of conventional IVR designs, such as the DPV IVR, involves significant technological and manufacturing hurdles. To meet these challenges, we have developed a novel IVR technology, the pod-IVR (19,21), that enables rapid development of devices capable of delivering multiple agents over a wide range of target delivery rates and levels of aqueous solubility (22)(23)(24)(25).Here, we report on the pharmacokinetics (PK) and preliminary local safety in an ovine model of a pod-IVR delivering the prodrug TFV disoproxil fumarate (TDF) in combination with maraviroc (MVC), an entry inhibitor/antagonist of chemokine receptor CCR5. Steady-state drug levels for both ARV agents in cervicovaginal fluids (CVFs) were sustained over the 28-day study with corresponding vaginal tissue (VT) concentrations above the levels required for putative efficacy in preventing HIV infection.

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Adherence Support Approaches in Biomedical HIV Prevention Trials: Experiences, Insights and Future Directions from Four Multisite Prevention Trials

Cited by 122 publications

References 23 publications

Preexposure Prophylaxis (PrEP) for HIV Prevention: The Primary Care Perspective

Preexposure Prophylaxis (PrEP) for HIV Prevention: The Primary Care Perspective

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

Combination Pod-Intravaginal Ring Delivers Antiretroviral Agents for HIV Prophylaxis: Pharmacokinetic Evaluation in an Ovine Model

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