Durable suppression of HIV replication is critical to (1) improving the health of infected individuals, (2) to reducing HIV transmission to sexual partners and from mothers to their infants, and (3) to maintaining the effectiveness of the current 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)- based ART. Across multiple trials, individuals with NNRTI-resistance, even at low-concentrations, have substantially greater virologic failure when treated with NVP vs. PI-ART. A cost-effective strategy is needed to detect and manage ARV-resistant HIV infections. A simple low-cost innovative assay we developed and successfully transferred to Asian and African countries (oligonucleotide ligation assay (OLA)) can detect NNRTI+lamivudine (3TC) resistant HIV using reagents that costs <$7.00/person. Furthermore, detection of NNRTI-resistance by OLA is highly (P<0.001) associated with virologic failure of nevirapine (NVP)-ART in two retrospective studies;one of Thai women who had been previously randomized to single-dose NVP and the second of ARV-na?ve Kenyan adults. Implementation of OLA into routine care we hypothesize will allow Kenyan clinicians to appropriately target protease inhibitor (PI)-based ART and improve rates of durable suppression of viral replication, and thus improve CD4 cell gains and individuals'health, reduce the transmission of ARV-resistant HIV within the community, and maintain the utility of NNRTI-ART. In addition, we hypothesize that programmatically OLA-guided ART will be more cost-efficient compared to the current strategy of empiric use of NNRTI-ART as initial treatment. Here we propose to gauge improvements in the rate of durable suppression of viral replication by ART when OLA is used to guide clinical decisions at the PEPFAR Coptic Hope Center in Kenya, and to determine the cost-effectiveness of implementing this strategy at Coptic Hope Center.

Public Health Relevance

A "cocktail" of medicines can treat HIV infection, transforming it from a lethal to a chronic infection. HIV - resistance to these medicines appears to be increasing in Africa and can undermine treatment. An inexpensive simple assay to detect HIV drug-resistance will be implemented in Kenya. We will study the benefits conferred by this assay to improving infected individuals health, and compare the overall cost of using to not using this test.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI100037-01
Application #
8298850
Study Section
Special Emphasis Panel (ZAI1-BP-A (J2))
Program Officer
Fitzgibbon, Joseph E
Project Start
2012-06-13
Project End
2015-05-31
Budget Start
2012-06-13
Budget End
2013-05-31
Support Year
1
Fiscal Year
2012
Total Cost
$934,685
Indirect Cost
$238,956
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105