Dataset Information

Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study

ABSTRACT:

Background

Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use.

Methods

All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Residual dapivirine remaining in the last ring returned by each participant was used to estimate drug released from the ring, which was then adjusted for time participants had the ring to calculate probable use categorized into three levels (low/intermittent/high). Product use was connected to PEA attendance using participant identification numbers. We used multivariate Poisson regression with robust standard errors to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs.

Results

2312 of 2629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (RR = 1.40) than those who never attended an event. There was a stronger correlation between a last returned ring showing use and participant attendance at multiple events (RR = 1.52).

Conclusions

Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

SUBMITTER: Garcia M

PROVIDER: S-EPMC8576984 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionA potential concern with the use of dapivirine (DPV) for HIV prevention is the selection of a drug-resistant virus that could spread and reduce the effectiveness of non-nucleoside reverse transcriptase (NNRTI)-based first-line antiretroviral therapy. We evaluated HIV-1 seroconversions in MTN-020/ASPIRE for selection of drug resistance and evaluated the genetic basis for observed reductions in susceptibility to DPV.MethodsMTN-020/ASPIRE was a placebo-controlled, Phase III safety and effectiveness study of DPV ring for HIV-1 prevention conducted at 15 sites in South Africa, Zimbabwe, Malawi and Uganda between 2012 and 2015. Plasma from individuals who seroconverted in ASPIRE was analysed for HIV-1 drug resistance using both population Sanger sequencing and next-generation sequencing (NGS) with unique molecular identifiers to report mutations at ≥1% frequency. DPV susceptibility of plasma-derived recombinant HIV-1 containing bulk-cloned full-length reverse transcriptase sequences from MTN-020/ASPIRE seroconversions was determined in TZM-bl cells. Statistical significance was calculated using the Fisher's exact test.ResultsPlasma from all 168 HIV seroconversions were successfully tested by Sanger sequencing; 57 of 71 DPV arm and 82 of 97 placebo (PLB) arm participants had NGS results at 1% sensitivity. Overall, 18/168 (11%) had NNRTI mutations including K101E, K103N/S, V106M, V108I, E138A/G, V179D/I/T and H221Y. Five samples from both arms had low-frequency NNRTI mutations that were not detected by Sanger sequencing. The frequency of NNRTI mutations from the DPV arm (11%) was not different from the PLB arm (10%; p = 0.80). The E138A mutation was detected in both the DPV (3 of 71 [4.2%]) and PLB arm (5 of 97 [5.2%]) and conferred modest reductions in DPV susceptibility in some reverse transcriptase backgrounds but not others.ConclusionsHIV-1 drug resistance including NNRTI resistance did not differ between the DPV and placebo arms of the MTN-020/ASPIRE study, indicating that drug resistance was not preferentially acquired or selected by the DPV ring and that the preventive benefit of DPV ring outweighs resistance risk.

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