Correlation Between Pill Counts and Biologic Effects in an HIV-1 Prevention Clinical Trial: Implications for Measuring Adherence.
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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ABSTRACT: Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence. In a placebo-controlled PrEP efficacy trial of tenofovir disoproxil fumarate(TDF) and TDF with emtricitabine(FTC/TDF) among 4747 African women and men with an HIV-infected partner, we measured plasma tenofovir concentrations from participants in the active PrEP arms: 29 HIV seroconverters (cases) and 196 randomly-selected controls who remained uninfected. Among controls, 71% of visits had tenofovir concentrations >40 ng/mL, consistent with steady-state daily dosing, compared to 32% of cases at the visit HIV was first detected. Pill count data indicated 96% of controls and 65% of cases had >80% adherence for these same visits. The estimated protective effect of PrEP against HIV, based on concentrations >40 ng/mL, was 88% (95%CI 60-96,p<0.001) for individuals receiving TDF and 91% (95%CI 47-98,p=0.008) for FTC/TDF. Controls had consistent patterns of PrEP concentrations during follow-up; amongst the 89% with concentrations >40 ng/mL at month 1, 75% maintained this concentration at month 12. Only five of 29 seroconverters appeared to be consistently adherent to PrEP. Tenofovir concentrations >40 ng/mL were associated with older age and shorter time on study; concentrations ≤40 ng/mL occurred more commonly when participants reported no sex with their HIV-infected partner. Plasma concentrations of tenofovir consistent with daily dosing were highly predictive of protection from HIV acquisition. Most of those who took PrEP appeared to have high and consistent adherence.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2014; DOI:10.1097/QAI.0000000000000172 · 4.39 Impact Factor
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ABSTRACT: Abstract A pilot study was conducted to determine effects of an empowerment intervention on antiretroviral therapy (ART) adherence among Thai youth living with HIV/AIDS. It compared two groups of 23 young persons (15-24 years) who receive ART from AIDS clinics at 2 community hospitals. One hospital's patients served as the experimental group, and the other as a control group. The experimental groups attended five sessions that empowered them to take control of their own health. The control group received standard of care. The data were analyzed using descriptive statistics and Chi-square statistics. Before the empowerment, no one from the experimental group or the control group had ART adherence ≥95%. After the intervention, the 82.6% of the experimental group had ≥95% adherence compared to the control group, which had 21.7% adherence (p<.0001). The empowerment intervention resulted in a significant increase in ART adherence among Thai youth.Behavioral Medicine 04/2014; DOI:10.1080/08964289.2014.911717 · 1.14 Impact Factor
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ABSTRACT: For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities. In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1-serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1-uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation, but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing. For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7 and 10.0% incidence per year, respectively; P-value for difference in effect by PrEP use = 0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; P-value for difference = 0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence <1% per year in both arms). PrEP had no adverse impact on hormonal contraceptive effectiveness for pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception and PrEP provide effective prevention for pregnancy and HIV-1.AIDS (London, England) 04/2014; 28(12). DOI:10.1097/QAD.0000000000000290 · 6.56 Impact Factor