Knowledge, Attitudes, and Experiences of HIV Pre-Exposure Prophylaxis (PrEP) Trial Participants in Botswana

Recent clinical trials have shown that a daily dose of oral TDF/FTC pre-exposure prophylaxis (PrEP) is effective in reducing human immunodeficiency (HIV) risk. Understanding trial participants’ perspectives about retention and PrEP adherence is critical to inform future PrEP trials and the scale-up and implementation of PrEP programs. We analyzed 53 in-depth interviews conducted in April 2010 with participants in the TDF2 study, a Phase 3, randomized, double-blind, place-bo-controlled clinical trial of daily oral TDF/FTC with heterosexual men and women in Francistown and Gaborone, Botswana. We examined participants’ knowledge, attitudes, and experiences of the trial, identified facilitators and barriers to enrollment and retention, and compared participant responses by study site, sex, and study drug adherence. Our findings point to several factors to consider for participant retention and adherence in PrEP trials and programs, including conducting pre-enrollment education and myth reduction counseling, providing accurate estimates of participant obligations and side effect symptoms, ensuring participant understanding of the effects of non-adherence, gauging personal commitment and interest in study outcomes, and developing a strong external social support network for participants.

Pitfall of genome-wide association studies: Sources of inconsistency in genotypes and their effects

Personalized medicine will improve heath outcomes and patient satisfaction. However, implementing personalized medicine based on individuals’ biological information is far from simple, requiring genetic biomarkers that are mainly developed and used by the pharmaceutical companies for selecting those patients who benefit more, or have less risk of adverse drug reactions, from a particular drug. Genome-wide Association Studies (GWAS) aim to identify genetic variants across the human genome that might be utilized as genetic biomarkers for diagnosis and prognosis. During the last several years, high-density genotyping SNP arrays have facilitated GWAS that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the studied phenotypic trait. The replication studies demonstrated that only a small portion of associated loci in the initial GWAS can be replicated, even within the same populations. Given the complexity of GWAS, multiple sources of Type I (false positive) and Type II (false negative) errors exist. The inconsistency in genotypes that caused either by the genotypeing experiment or by genotype calling process is a major source of the false GWAS findings. Accurate and reproducible genotypes are paramount as inconsistency in genotypes can lead to an inflation of false associations. This article will review the sources of inconsistency in genotypes and discuss its effect in GWAS findings.