Immune restoration in HIV-positive, antiretroviral-naive patients after 1 year of zidovudine/lamivudine plus nelfinavir or nevirapine.

OBJECTIVES: To evaluate the immunological response in HIV-1-infected, antiretroviral-naive patients receiving highly active antiretroviral therapy regimen of two nucleosides plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor. DESIGN AND METHODS: Of 142 patients included in a randomized, open, multicentre trial comparing zidovudine/lamivudine plus nelfinavir (NFV) or nevirapine (NVP), 36 patients (16 NFV, 20 NVP) were enrolled in an immunological substudy. Mean baseline CD4 T-cell counts was 360/mm3 (range: 11-679) and mean baseline plasma viral load >50000 copies/ml (range: 2240-1468210). Viral load (VL), T-cell subsets and T-cell functions were analysed at baseline and after 1 year of treatment. RESULTS: After 12 months of follow-up, plasma viral load was reduced similarly in both groups, with 78% (NFV) and 83% (NVP) of patients achieving a VL <200 copies/ml. A significant increase in CD4 T cells was observed in both groups (mean: +182 cells, P=0.001). Both regimens were similarly effective in reducing activated T cells (CD38 and DR). A significant increase of both CD4 and CD8 CD28 T cells occurred in both arms of treatment. Patients of both regimens showed a significant decrease of activated memory (CD45RA-CD45RO+) CD8 T cells and a clear increase of naive (CD45RA+CD45RO-) CD8 T cells. Peripheral blood mononuclear cell proliferative responses to polyclonal stimuli (CD3 and CD3 +CD28) as well as to ubiquitous cytomegalovirus antigen increased significantly in both groups after 12 months of follow-up. Nevertheless, neither at baseline nor after 1 year of treatment, these patients showed any significant T-cell responsiveness to HIV-1 recombinant proteins gp160 or p24. CONCLUSIONS: Our data indicate that immune restoration achieved after 1 year of therapy with either NFV or NVP was similar. This reinforces the role of NVP-containing regimens as a valid option for initiating antiretroviral therapy. Nevertheless, additional therapeutic approaches should be envisaged to restore HIV-1-specific T-cell responses.

A comparison of the effects of nevirapine and nelfinavir on metabolism and body habitus in antiretroviral-naive human immunodeficiency virus-infected patients: a randomized controlled study.

New HIV therapies have significantly increased survival, but are associated with multiple metabolic changes, most of them related to the protease inhibitors (PIs). The objective of this study was to elucidate and compare morphological and metabolic alterations in HIV-infected antiretroviral-naive patients receiving two nucleosides plus the PI nelfinavir (NFV) or the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP). Forty-three patients (NFV, n = 20; NVP, n = 23) receiving 6-12 months of treatment were analyzed. Morphological changes were evaluated by bioelectrical impedance analysis, standard anthropometrics, and clinical examination. Serum total cholesterol (TC), low-density and high- density (HDL-c) lipoprotein cholesterol, triglycerides, glucose, and insulin were determined, among other metabolic parameters. No baseline differences were observed between groups. TC increased in both arms (NVP, 11%; NFV, 17%). HDL-c also increased in both groups, although more markedly in those receiving NVP (44% vs. 20%); on-treatment levels were also elevated (1.57 vs. 1.28 mmol/liter). As a consequence of these changes, the TC/HDL-c ratio dropped by 22% in the NVP arm and remained stable in the NFV group. With the use of NFV, the TC/HDL-c ratio and attendant cardiovascular risk did not change. In contrast, NVP offered benefits regarding lipid status, as manifested by enhanced HDL-c concentrations and decreased TC/HDL-c ratios. Inclusion of NVP should be considered when deciding upon antiretroviral regimens for patients at high coronary risk.

Genotype and phenotype at baseline and at failure in human immunodeficiency virus-infected antiretroviral-naive patients in a randomized trial comparing zidovudine and lamivudine plus nelfinavir or nevirapine.

For the 127 Spanish patients enrolled in the Combine Study, a resistance substudy was performed with 100 (79%) plasma samples obtained at baseline and with 18 samples obtained from 19 patients at the time they experienced treatment failure. At baseline, primary mutations to nonnucleoside reverse-transcriptase inhibitors and protease inhibitors were not detected, whereas mutations to nucleoside reverse-transcriptase inhibitors were observed in 10% of patients. At failure, mutations were detected in 7 of 16 patients. An agreement in the results of virtual and real phenotypes was observed in the 93 samples in which both tests were performed.