The Fitness Cost to Human Immunodeficiency Virus Type 1 of Escaping From a Small Molecule CCR5 Inhibitor

Replicative fitness of an HIV-1 isolate generally tracks to the region of the genome that is under the most selective pressure. During HIV-1 infection, significant selection pressure is applied by the immune system causing sequence changes in the env gene. The clinical use of entry inhibitors will add to this pressure. Drug selection pressure can often force the virus to compromise its fitness in favor of acquiring resistance. This loss of fitness may lead to lower viral loads in vivo despite high levels of drug resistance. If the virus has already undergone compromises to survive in the face of the immune response, the additional changes in env may cause a significant reduction in replicative capacity. This presentation will focus on in vitro evaluation of the replicative fitness of HIV-1 isolates resistant to entry inhibitors and possible implications of such findings.