ABSTRACT
Eight-day inpatient directly observed therapy confirmed nonadherence as the major cause of virologic failure for 9 (45%) of 20 highly treatment-experienced persons with human immunodeficiency virus, extensive antiretroviral drug resistance, and high self-reported adherence rates, preventing unnecessary regimen changes.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Directly Observed Therapy , Drug Resistance, Viral , HIV Infections/drug therapy , Humans , Inpatients , Medication Adherence , Treatment Failure , Viral LoadABSTRACT
The integrase strand transfer inhibitor (INSTI) dolutegravir is commonly used in combination antiretroviral therapy regimens and retains strong potency even with primary resistance mutations to some other INSTIs. Acquisition of accessory mutations to primary mutations results in significant increases in dolutegravir resistance. Previously, we reported that addition of the secondary mutation T97A can result in rapid treatment failure in individuals with INSTI mutations at positions 140 and 148. Here, we conducted a detailed case study of one of these individuals and find that T97A-containing HIV emerged from a large replicating population from only a few (≤4) viral lineages. When combined with primary INSTI resistance mutations, T97A provides a strong selective advantage; the finding that T97A-containing variants spread by replication and recombination, and persisted for months after discontinuing dolutegravir, has important implications as dolutegravir is rolled out worldwide.
Subject(s)
HIV Infections , HIV Integrase Inhibitors , HIV Integrase , HIV-1 , Quinolones , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV Integrase/genetics , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , HIV-1/genetics , Heterocyclic Compounds, 3-Ring/pharmacology , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Mutation , Oxazines , Piperazines , Pyridones/therapeutic use , Quinolones/pharmacology , Recombination, Genetic , Salvage TherapyABSTRACT
Underrepresentation of HIV-infected Hispanics and African Americans in clinical trials seriously limits our understanding of the benefits and risks of treatment in these populations. This qualitative study examined factors that racial/ethnic minority patients consider when making decisions regarding research participation. A total of 35 HIV-infected Hispanic and African American patients enrolled in clinical research protocols at the National Institutes of Health were recruited to participate in focus groups and in-depth interviews. The sample included mostly male participants (n = 22), had a mean age of 45, had nearly equal representation of race/ethnicity, and were diagnosed 2 to 22 years earlier. Baseline questionnaires included demographics and measures of social support and acculturation. Interviewers had similar racial/ethnic, cultural, and linguistic backgrounds as the participants. Four major themes related to the decisions of participants to enroll in clinical trials emerged, which are as follows: enhancers, barriers, beliefs, and psychosocial context. Results may help researchers develop strategies to facilitate inclusion of HIV-infected Hispanics and African Americans into clinical trials.
Subject(s)
Black or African American/psychology , Clinical Trials as Topic , Decision Making , HIV Infections/psychology , Hispanic or Latino/psychology , Adult , Female , Focus Groups , Humans , Male , Middle Aged , Social Justice , United StatesABSTRACT
HIV infection occurs in disproportionately high rates among racial and ethnic minorities in the United States, making it imperative that individuals from these groups be included in research studies. However, it is often difficult to recruit HIV-infected Hispanics and African Americans in clinical trials, but a skilled interdisciplinary team that includes researchers with racial and ethnic diversity can help. This article describes a successful approach for building an interdisciplinary team that values the participation of racial and ethnic minorities in clinical trials and has the skills to work with these groups. The success of the Adelante (a Spanish word meaning forward) Team can be attributed to team members who actively participate in decision-making, are empowered, and function in a cohesive manner. Successful research teams build relationships with research participants to increase the probability that racial and ethnic minorities will enroll and participate fully in research.