Know Your Enemy—amfAR Grantees Study HIV Mutation and Drug Resistance
By Jeffrey Laurence, M.D.
March 2008—One factor that makes HIV such an elusive pathogen is its extremely high rate of change. Such mutations are major impediments to drug development and vaccine design. In the February issue of AIDS Research and Human Retroviruses, amfAR grantee Dr. Jayanta Bhattacharya and colleagues report novel instances of such genetic change in India.
Bhattacharya’s group at the National AIDS Research Institute in Pune, India, describes the mixing of genes from two subtypes of HIV-1. Such mixing, known as recombination, may create strains differing in transmission rates, response to drugs, or disease-causing potential. It certainly complicates attempts to define country-specific AIDS vaccines.
HIV recombination had been known for many years. What was unique about this report was the origin of the two HIV types involved: type C, predominant in India, and type B, which—though characteristically found in the U.S. and western Europe— resembled a form in this instance that had established a foothold in Thailand.
Dr. Bhattacharya and colleagues reasoned that this was an example of the impact of globalization. “Different genetic subtypes of HIV-1 that were geographically isolated in the past are being introduced in the same population probably due to augmented intercontinental and intracontinental population migration, tourism, and conglomerate enterprises,” they wrote. These movements will only increase—yet another reason to emphasize HIV prevention strategies.
Writing in the same issue of AIDS Research and Human Retroviruses, amfAR fellow Dr. Ryan Troyer of Case Western Reserve University studied another aspect of viral change: drug resistance. Using a highly sensitive method to detect mutations among virus variants that represent only a small fraction of virus present in a patient, Dr. Troyer and associates studied HIV-positive mothers and their infants in Uganda who were either untreated or received short courses of AZT or nevirapine in an attempt to block mother-to-infant transmission of HIV.
It is known that use of nevirapine in this manner is associated with development of drug resistance mutations. Dr. Troyer found that the two major gene changes responsible for such resistance were also present in a significant portion of HIV-positive mothers who had never taken an anti-HIV drug. This suggests that the effectiveness of nevirapine in treatment, or in prevention of mother-to-infant transmission of HIV in subsequent pregnancies, may be compromised in this region of the world and deserves further study.
The urgency of concern over the extent of preexisting AZT and/or nevirapine mutations was highlighted in a March 9 New York Times story concerning the failure of single drug regiments to prevent mother-to-child transmission and the South African government’s failure to provide the highly effective AZT/nevirapine combination.
Dr. Jeffrey Laurence is amfAR’s senior scientific consultant.