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To determine the short-term effects of using genotypic antiretroviral resistance testing (GART) with expert advice in the management of patients failing on a protease inhibitor and two nucleoside reverse transcriptase inhibitors.Prospective randomized controlled trial.Multicenter community-based clinical trials network.One-hundred and fifty-three HIV-infected adults with a threefold or greater rise in plasma HIV-1 RNA on at least 16 weeks of combination antiretroviral therapy.Randomization was either to a GART group, where genotype interpretation and suggested regimens were provided to clinicians, or to a no-GART group, where treatment choices were made without such input.Plasma HIV-1 RNA levels and CD4 cell counts were measured at 4, 8, and 12 weeks following randomization. The primary endpoint was change in HIV-1 RNA levels from baseline to the average of the 4 and 8 week levels.The average baseline CD4 cell count was 230 x 10(6) cells/l and the median HIV-1 RNA was 28,085 copies/ml. At entry, 82 patients were failing on regimens containing indinavir, 51 on nelfinavir, 11 on ritonavir, and nine on saquinavir. HIV-1 RNA, averaged at 4 and 8 weeks, decreased by 1.19 log10 for the 78 GART patients and -0.61 log10 for the 75 no-GART patients (treatment difference: -0.53 log, 95% confidence interval, -0.77 to -0.29; P = 0.00001). Overall, the best virologic responses occurred in patients who received three or more drugs to which their HIV-1 appeared to be susceptible.In patients failing triple drug therapy, GART with expert advice was superior to no-GART as measured by short-term viral load responses.

Cytotoxic T-lymphocytes (CTL) appear to be an important defense mechanism against HIV infection. This study proposes to examine the major histocompatibility complex (MHC)-restricted HIV-1 Env-, Gag- and Pol-specific CTL activities in HIV-infected asymptomatic patients.CD4+ and CD8+ CTL were examined to establish whether the same HIV-1 protein (Env, Gag or Pol) was recognized by both CD4+ and CD8+ CTL with MHC antigen restriction.Peripheral blood mononuclear cells, CD4+ and CD8+ T-cells from 17 HIV-infected asymptomatic patients and 10 HIV-seronegative individuals were examined for HIV-1 Env-, Gag- and Pol-specific MHC-restricted cytotoxicity using autologous and heterologous B-lymphoblastoid cell lines infected with vaccinia recombinant expressing HIV-1 Env, Gag and Pol proteins as targets.CD4+ and CD8+ CTL specific for the HIV-1 Env, Gag and Pol were demonstrated in the peripheral blood. DR4 and DQw2 were possible sites of MHC class II restriction of CD4+ CTL. Possible MHC class I restriction sites of CD8+ CTL included A2 and B8 for Env, A1 and A2 for Gag, and A2 and B8 for Pol antigen.These observations should help to define more precisely the nature and elements of protective immunity and to evaluate AIDS vaccine strategies.