Article

Correlation Between Pill Counts and Biologic Effects in an HIV-1 Prevention Clinical Trial: Implications for Measuring Adherence

Department of Global Health, University of Washington, Seattle, WA, USA, .
AIDS and Behavior (Impact Factor: 3.49). 08/2012; 17(2). DOI: 10.1007/s10461-012-0268-0
Source: PubMed

ABSTRACT Clinic-based pill counts of unused study medication are frequently used to measure adherence in HIV-1 prevention trials. Monthly pill count adherence data from the Partners in Prevention HSV/HIV Transmission Study, a double-blind, placebo controlled trial of twice-daily acyclovir suppression of herpes simplex virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes between 3,381 placebo and active arm participants in two objective biologic measures of acyclovir's drug activity: reduction in plasma HIV-1 RNA and HSV-2 genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data is strongly correlated with biological effects of adherence. However, when calculated adherence exceeded 102 % (i.e., fewer pills returned than expected) and when pill counts were missing because bottles were not returned, plasma HIV-1 RNA and GUD effects were diminished, likely indicating periods of non-adherence.

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    • "In both trials, although the biological markers of genital herpes reactivation were different (PCR confirmed GUD in HPTN 039 and HSV-2 shedding ascertained at 3 time points in Mwanza), we found that the effect of acyclovir on biologic measures of anti-HSV-2 activity was similar among participants with pill counts that suggested adherence >105 % and those with adherence <90 %, and lower than those with 90–105 % adherence. This is consistent with recently-reported findings from the Partners in Prevention HSV/HIV Transmission Study, in which low and apparent over-adherence to acyclovir in HIV/HSV-2 dually infected persons was associated with a reduced effect on HIV-1 plasma viral load and HSV-2 GUD [26]. Acyclovir suppression significantly but incompletely reduces symptomatic genital ulcers and HSV-2 shedding, so both are imperfect markers of adherence and drug exposure [27]. "
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    ABSTRACT: For trials of user-dependent HIV prevention products, accurate adherence measurements are essential to interpret and compare results across trials. We used pill count data from two recent HIV prevention trials of herpes simplex virus type 2 (HSV-2) suppression, to show that estimates of adherence vary substantially depending on assumptions that are made in analysing pill count data. We associate calculated adherence with biological markers of anti-HSV-2 activity. In both trials, calculated adherence varied considerably, depending on the summary measure used, and the handling of intervals with apparent 'over-adherence' (fewer pills returned than expected), and unreturned pills. Intervals of apparent over-adherence were associated with reduced antiviral effects on biological markers of herpes reactivation, indicating these are likely to represent periods of non-adherence. Our results demonstrate the clear need for standardisation in reporting of adherence data that are based on pill counts.
    AIDS and Behavior 06/2013; 17(9). DOI:10.1007/s10461-013-0542-9 · 3.49 Impact Factor
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