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Antiretroviral Drug Resistance

Sponsor

The Fogarty International Center, National Institutes of Health (NIH)

Staff

Dr. Paul Shekelle

Antiretroviral drugs (ARVs) are among the most effective agents for the treatment of HIV/AIDS. However, they do not destroy the virus completely. The survival and emergence of drug resistant strains is one of the primary causes for treatment failure and the further spread of the infection. The Southern CA Evidence-Based Practice Center was asked to conduct a literature search and to synthesize the available evidence on antiretroviral drug resistance. In particular, they were asked to address the following key questions:

1. What is the prevalence of resistance? Does the prevalence of resistance differ between adults and children? Between men and women? Between groups with differing modes of transmission?
2. What are the factors associated with the development of resistance? How do the factors different among varying population groups?
3. a. Viral factors (e.g., viral subtype — MTCT data indicate major differences in risk of NVP resistance after single dose nevaripine (SD NVP) between subtypes C>D>A; superinfection)
   
   

   b. Host factors (e.g., could put prior MTCT intervention here maybe, gender, mode transmission, other host factors like immune status, genetics?)

   c. ARVs (e.g., specific ARV or ARV class, fixed dose combinations, drug interactions)

   d. Resistance assay (e.g., standard bulk testing vs. ultrasensitive testing)

   e. "Health service associated" (e.g., stock-out, inability to pay, access, delivery, availability of drug outside of health system).

   
   
   
4. What are effective strategies to prevent or reduce the development of resistance in different population groups (e.g. HIV-positive or HIV-exposed women who have recently given birth after interventions intended to prevent mother-to-child transmission [PMTCT]; people receiving ARV, etc.)?
5. What is the likely impact of low level or partial resistance on subsequent therapy? What is the impact on response to subsequent PMTCT interventions?

A final report is expected in late 2006.