In 2014, UNAIDS introduced the ?90-90-90? targets for HIV control, including that 90% of those on ART are virologically suppressed. In order to reach these treatment goals, additional progress will need to be made in sub-Saharan Africa, where rates of 1st-line antiretroviral treatment (ART) failure are reportedly as high as 1 in 3 individuals and increasing rates of drug resistance are complicating efforts to effectively treat these patients. For patients experiencing virologic failure (VF) on 1st-line ART, there is currently uncertainty over which individuals should be maintained on their 1st-line ART regimen and who should be switched to a 2nd-line regimen. Multiple studies have indicated that traditional Sanger-based genotypic testing might not accurately predict clinical outcomes in these situations. VF commonly occurs in those taking regimens with a high genotypic susceptibility scores (GSS) as determined by standard Sanger sequencing techniques, and conversely, virologic suppression often occurs in patients on regimens with a low GSS. This study brings together an experienced team of clinical researchers, virologists, pharmacologists, and biostatisticians from the United States and Africa to determine the predictors of VF either with maintenance of 1st-line ART or after switch to 2nd-line ART. This study will leverage stored samples from existing clinical trials combined with innovative viral sequencing and pharmacologic technologies to assess the risk of VF with either approach. The proposed studies will directly address key knowledge gaps related to drug resistance and medication adherence, and are ultimately intended to improve the clinical management of patients with 1st-line ART failure in sub-Saharan Africa. Optimizing treatment strategies in this population is critical for preventing drug resistance, controlling the epidemic, and ensuring the long-term sustainability of HIV programs.

Public Health Relevance

To reach the UNAIDS ?90-90-90? treatment goals, improved rates of virologic suppression are needed in sub- Saharan Africa, where the majority of HIV-positive individuals live and where virologic failure (VF) on 1st-line antiretroviral treatment (ART) occurs in up to 1 in 3 individuals. This study brings together an experienced team of clinical researchers, virologists, pharmacologists, and biostatisticians from the United States and Africa to determine the predictors of VF either with maintenance of 1st-line ART or after switch to 2nd-line ART. Optimizing treatment strategies in sub-Saharan Africa for patients with VF on 1st-line ART regimens is critical for preventing drug resistance, controlling the epidemic, and ensuring the long-term sustainability of HIV programs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI138801-01A1
Application #
9623714
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Crawford, Keith W
Project Start
2018-07-06
Project End
2022-06-30
Budget Start
2018-07-06
Budget End
2019-06-30
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code