This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DESIGN: A5173 is a limited-site, single-arm pilot study to measure the clearance of replication-competent HIV-1 in resting memory CD4+ cells in treatment-naive HIV-1-infected subjects who then have HIV-1 RNA levels suppressed while receiving a fusion inhibitor (enfuvirtide, formerly T-20) + inhibitors of reverse transcriptase and protease. DURATION: 96 weeks SAMPLE SIZE: 40 subjects POPULATION: HIV-1-infected individuals with plasma HIV-1 RNA levels ?1000 copies/mL and CD4+ cell counts ?100 cells/mm3, and who have had ?7 days of any other antiretroviral therapy. Subjects will be ineligible if there is evidence of recent HIV-1 seroconversion, or if the screening genotype shows the existence of a primary resistance mutation in reverse transcriptase or protease. REGIMEN: Enfuvirtide 90 mg sq BID + tenofovir 300 mg po QD + emtricitabine 200 mg po QD + saquinavir hard gel capsules 1000 mg po BID + ritonavir 100 mg po BID. Subjects and their health care providers may choose another protease inhibitor for the regimen; however, only saquinavir and ritonavir will be provided by the study. Subjects who entered under Version 1.0 may continue to take lamivudine or may switch to the study-provided emtricitabine. All subjects will have their latent cell reservoir sampled at week 24 except those who have permanently discontinued enfuvirtide or all study medications. Subjects who achieve a plasma HIV-1 RNA of 50 copies/mL at week 24 will have their latent cell reservoir sampled at weeks 48, 72, and 96. Subjects who do not achieve a plasma HIV-1 RNA of 50 copies/mL at week 24 will be followed but will not undergo additional evaluation of the latent cell reservoir. These subjects may continue to receive study medications, including enfuvirtide, and will have safety monitoring as outlined in the protocol. They will be allowed to modify their regimen at their provider?s discretion in consultation with the study team. Subjects who have a plasma HIV-1 RNA 50 copies/mL at week 24 and throughout the duration of the study, or who have single measurements ?50 copies/mL but who are 50 copies/mL when retested, will be the primary focus of this study. Subjects who have a confirmed plasma HIV-1 RNA ?50 copies/mL after week 24 that is not confirmed to be ?200 copies/mL will have the option of undergoing treatment intensification at their provider?s discretion in consultation with the study team, and they will continue to have samples obtained for latent reservoir assays. Subjects who have two consecutive viral loads ?200 copies/mL after week 24 will have met the protocol definition of virologic failure and will no longer contribute samples for the latent reservoir analysis. These subjects may continue to receive study medications, including enfuvirtide, and will have safety monitoring as outlined in the protocol. They will be allowed to modify their regimen at their provider?s discretion in consultation with the study team. Within-class drug substitutions will be allowed for toxicity, tolerability, and/or adherence difficulty. Note: For the purposes of this study, nucleoside and nucleotide analogues will be considered to be in the same class.
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