Adherence in the CAPRISA 004 Tenofovir Gel Microbicide Trial

Mansoor, Leila E.; Karim, Quarraisha Abdool; Yende‐Zuma, Nonhlanhla; MacQueen, Kathleen M.; Baxter, Cheryl; Madlala, Bernadette T.; Grobler, Anneke; Karim, Salim S. Abdool

doi:10.1007/s10461-014-0751-x

Cited by 23 publications

(27 citation statements)

References 27 publications

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“…In lieu of a vaccine, FDA-approved PrEP comprised of two NRTIs can reduce infections in high-risk populations (2)(3)(4)(5)7). However, the most significant barrier to PrEP efficacy is patient adherence, as Ͼ90% protection is observed in patients with consistently detectable plasma drug concentrations, whereas no protection is seen in participants showing undetectable drug concentrations (2,4,6,8,59,60). To improve adherence, long-acting injectable nanoparticle formulations of RPV have been developed and are currently being evaluated in clinical trials (13).…”

Section: Discussionmentioning

confidence: 99%

Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

Melody

McBeth

Kline

et al. 2015

Antimicrob Agents Chemother

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c Preexposure prophylaxis (PrEP) using antiretroviral drugs is effective in reducing the risk of human immunodeficiency virus type 1 (HIV-1) infection, but adherence to the PrEP regimen is needed. To improve adherence, a long-acting injectable formulation of the nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV LA) has been developed. However, there are concerns that PrEP may select for drug-resistant mutations during preexisting or breakthrough infections, which could promote the spread of drug resistance and limit options for antiretroviral therapy. To address this concern, we administered RPV LA to macaques infected with simian immunodeficiency virus containing HIV-1 RT (RT-SHIV). Peak plasma RPV levels were equivalent to those reported in human trials and waned over time after dosing. RPV LA resulted in a 2-log decrease in plasma viremia, and the therapeutic effect was maintained for 15 weeks, until plasma drug concentrations dropped below 25 ng/ml. RT mutations E138G and E138Q were detected in single clones from plasma virus in separate animals only at one time point, and no resistance mutations were detected in viral RNA isolated from tissues. Wild-type and E138Q RT-SHIV displayed similar RPV susceptibilities in vitro, whereas E138G conferred 2-fold resistance to RPV. Overall, selection of RPV-resistant variants was rare in an RT-SHIV macaque model despite prolonged exposure to slowly decreasing RPV concentrations following injection of RPV LA.

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Section: Discussionmentioning

confidence: 99%

Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

Melody

McBeth

Kline

et al. 2015

Antimicrob Agents Chemother

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“…Regarding PEP, the main concern is in ensuring a broad knowledge to assure its use in time, as well as is investing in adherence, which is also central for PrEP. For this second technology, it is also necessary to analyze which groups may benefit more of its use, because its effectiveness among women, for example, remains questionable, although it may become appropriate to their daily routines for topical use, as promising studies have been indicating 42 . In the case of treatment for PLHA, although the high level of protection offered may lead to the belief that its adoption outweighs the risks of behavioral aspects resulting in the increased of HIV incidence, once more adherence appears as the main challenge, because the achievement and sustaining of viral suppression depend on it 43 .…”

Section: Resultsmentioning

confidence: 99%

Sex, human rights and AIDS: an analysis of new technologies for HIV prevention in the Brazilian context

Ferraz

Paiva

2015

Rev. bras. epidemiol.

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Worldwide, HIV prevention is challenged to change because clinical trials show the protective effect of technologies such as circumcision, preexposure prophylaxis, and the suppression of viral load through antiretroviral treatment. In the face of demands for their implementation on population levels, the fear of stimulating risk compensation processes and of increasing riskier sexual practices has retarded their integration into prevention programs. In this article, following a narrative review of the literature on risk compensation using the PubMed database, we offer a critical reflection on the theme using a constructionist approach of social psychology integrated to the theoretical framework of vulnerability and human rights. The use of biomedical technologies for prevention does not consistently induce its users to the increase of riskier practices, and variations on the specificity of each method need to be carefully considered. Alternatives to the theories of sociocognitive studies, such as social constructionist approaches developed in the social sciences and humanities fields, indicate more comprehensive interpretations, valuing the notions of agency and rights. The critical analysis suggests priority actions to be taken in the implementation process: development of comprehensive programs, monitoring and fostering dialog on sexuality, and technical information. We highlight the need to implement a human rights-based approach and to prioritize dialog, stressing how complementary these technologies can be to meet different population needs. We conclude by stressing the need to prioritize sociopolitical changes to restore participation, dialog about sexuality, and emphasis on human rights such as core elements of the Brazilian AIDS policy.

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“…Notably, some adherence challenges to the BAT 24 peri-coital gel dosing used in CAPRISA are likely to be different than those for daily gel use. CAPRISA's adherence support program was denoted by a change in staff providing counseling as well as the introduction of several tools and aids during the counseling sessions [22]. In VOICE, adherence was already very low at the time VASP was implemented, no new tools or aids were introduced, the same counseling staff delivered the new intervention, and counselor-specific meetings and in-person debriefing varied in frequency.…”

Section: Discussionmentioning

confidence: 99%

Perceptions and Experiences with the VOICE Adherence Strengthening Program (VASP) in the MTN-003 Trial

et al. 2014

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The VOICE Adherence Strengthening Program (VASP) was implemented in May 2011 to improve adherence counseling in VOICE (MTN-003), a multisite placebo-controlled trial of daily oral or vaginal tenofovir-based Pre-Exposure Prophylaxis (PrEP). Anonymous baseline (N = 82) and final follow-up (N = 75) surveys were administered to counselors and pharmacists at 15 VOICE sites, and baseline (N = 18) and final (N = 26) qualitative in-depth interviews were conducted with purposively selected counseling staff at 13 VOICE sites. Qualitative interviews with VOICE participants (N = 38) were also analyzed for segments related to counseling. Behavioral and biological measures of product use collected in the 6 months prior to VASP implementation were compared to those collected during the 6 months following implementation. Results show that the majority of staff preferred VASP and thought that participants preferred VASP over the previous education and counseling strategy, although there was no evidence to suggest that participants noticed modifications in the counseling approach. No meaningful changes were observed in pre/post levels of reported use or drug detection. Interpretation of results is complicated by mid-trial implementation of VASP and its proximity to early closure of oral and vaginal tenofovir study arms because of futility.

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Adherence in the CAPRISA 004 Tenofovir Gel Microbicide Trial

Cited by 23 publications

References 27 publications

Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

Low Frequency of Drug-Resistant Variants Selected by Long-Acting Rilpivirine in Macaques Infected with Simian Immunodeficiency Virus Containing HIV-1 Reverse Transcriptase

Sex, human rights and AIDS: an analysis of new technologies for HIV prevention in the Brazilian context

Perceptions and Experiences with the VOICE Adherence Strengthening Program (VASP) in the MTN-003 Trial

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