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Short Communication: Practical Experience with Analysis and Design of Repeat Low-Dose SHIVSF162P3 Exposure Studies in Female Pigtail Macaques with Varying Susceptibility During Menstrual Cycling.

Abstract：

:Vaginal SHIVSF162P3 acquisition in pigtail macaques (Macaca nemestrina) is dependent on time point during the menstrual cycle. Susceptibility is higher around menstruation and lower at ovulation in mid cycle. This complicates the design of repeat low-dose (RLD) SHIV exposure studies because virus challenges given during low susceptibility periods have lower chances to infect. To account for fluctuating susceptibility, we analyzed menstrual cycles rather than exposures until infection following virus challenges. We first reanalyzed infection data of 41 macaques receiving placebo or no treatment during once (n=18) or twice (n=23) weekly virus exposures. The same number of cycles was required for infection with either challenge frequency, while it took a median four or six challenges for once or twice weekly exposures, respectively. More virus challenges to infection likely reflect frequent unsuccessful exposures in frequently exposed animals. When reanalyzing two previously reported biomedical HIV intervention studies, we found 1% tenofovir gel was 74% or 86% efficacious based on cycles or exposures (p=0.019 or p=0.003, respectively, Fisher's exact test), while 1% raltegravir gel was 84% or 89 % efficacious, respectively (p=0.047 or p=0.031). Evaluating the number of menstrual cycles rather than exposures until infection can account for varying susceptibility during the menstrual cycle. Our observations have implications for future study designs such as planning the frequency of virus exposures. Menstrual cycle analysis may also avoid potential overestimation of efficacy against vaginal challenges during low susceptibility periods in the cycle that are unlikely to cause infection.

journal_name

AIDS Res Hum Retroviruses

journal_title

AIDS research and human retroviruses

authors

Kersh EN,Henning TR,Dobard C,Heneine W,McNicholl JM

doi

10.1089/AID.2014.0373

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1166-9

issue

eissn

0889-2229

issn

1931-8405

journal_volume

pub_type

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Short Communication: Practical Experience with Analysis and Design of Repeat Low-Dose SHIVSF162P3 Exposure Studies in Female Pigtail Macaques with Varying Susceptibility During Menstrual Cycling.