Inexpensive HIV Resistance Testing

HIV resistance to antiretroviral medications can be transmitted between individuals and is called transmitted drug resistance (TDR). TDR can spread in a population, rendering first-line antiretroviral medications obsolete.

As the prevalence of TDR and general antiretroviral resistance increases in resource-limited settings, inexpensive laboratory assays are needed to detect resistant virus to guide clinicians and their prescribing practices;

1. Durable suppression of HIV replication is critical to 1) Improving the health of infected individuals

2. Reducing HIV transmission to sexual partners and from mothers to their infants, and

3. Maintaining the effectiveness of the current 1st line non-nucleoside reverse transcriptase inhibitors (NNRTI) –based antiretroviral therapy (ART).

TREE is collaborating with Dr. Lisa Frenkel at Seattle Children’s Hospital to examine HIV resistance, TDR, and the use of Oligonucleotide Ligation Assay (OLA) as an inexpensive test to detect drug resistance in Nairobi, Kenya.  The OLA test includes a chain reaction (PCR) followed by an enzyme-linked assay (EIA). OLA can detect resistance at 4 pol codons conferring high-level resistance to NNRTI and Lamivudine (3TC)-(K103N, Y181C, G190A and M184V).

Previous studies have verified the efficacy of OLA to detect baseline TDR and predict virologic failure among antiretroviral-naïve patients and women who have been exposed to perinatal Nevirapine, when compared to pyrosequencing and consensus sequencing.

TREE is implementing an R01-funded randomized clinical trial at Coptic Hope Center to determine the effect of OLA testing prior to initiation of antiretroviral therapy to prevent virologic failure. This trial is enrolling over 900 men, women, and children in Kenya and randomizing them to receive OLA vs. no OLA testing and following them over 18 months. The implementation of the OLA test prior to initiating treatment will allow the Kenyan clinicians to appropriately target protease inhibitor (PI) based ART treatment. In addition, TREE is assessing the cost effectiveness of OLA guided therapy versus empiric use of NNRTI-ART as initial treatment.