ABSTRACT
BACKGROUND: It is unclear whether therapy for human immunodeficiency virus type 1 (HIV-1) should be initiated with a four-drug or two sequential three-drug regimens. METHODS: In this multicenter trial we compared initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine with therapy involving two consecutive three-drug regimens the first of which contained either efavirenz or nelfinavir. RESULTS: A total of 980 subjects were followed for a median of 2.3 years. There was no significant difference in the occurrence of regimen failures between the group that received the four-drug regimen containing didanosine, stavudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with didanosine, stavudine, and nelfinavir (hazard ratio for regimen failure, 1.24) or didanosine, stavudine, and efavirenz (hazard ratio, 1.01). There was no significant difference between the group that received the four-drug regimen containing zidovudine, lamivudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with zidovudine, lamivudine, and nelfinavir (hazard ratio, 1.06) or zidovudine, lamivudine, and efavirenz (hazard ratio, 1.45). A four-drug regimen was associated with a longer time to the first regimen failure than the three-drug regimens containing didanosine, stavudine, and nelfinavir (hazard ratio for a first regimen failure, 0.55); didanosine, stavudine, and efavirenz (hazard ratio, 0.63); or zidovudine, lamivudine, and nelfinavir (hazard ratio, 0.49), but not the three-drug regimen containing zidovudine, lamivudine, and efavirenz (hazard ratio, 1.21). CONCLUSIONS: There was no significant difference in the duration of successful HIV-1 treatment between a single four-drug regimen and two consecutive three-drug regimens. Among these treatment strategies, initiating therapy with the three-drug regimen of zidovudine, lamivudine, and efavirenz is the optimal choice.
Subject(s)
Anti-Retroviral Agents/administration & dosage , HIV Infections/drug therapy , HIV-1 , Adult , Alkynes , Anti-Retroviral Agents/adverse effects , Anti-Retroviral Agents/therapeutic use , Benzoxazines , CD4 Lymphocyte Count , Cyclopropanes , Didanosine/administration & dosage , Double-Blind Method , Drug Resistance, Viral/genetics , Drug Therapy, Combination , Female , HIV-1/genetics , Humans , Lamivudine/administration & dosage , Male , Mutation , Nelfinavir/administration & dosage , Oxazines/administration & dosage , Stavudine/administration & dosage , Time Factors , Treatment Failure , Zidovudine/administration & dosageABSTRACT
OBJECTIVE(S): Depletion of thymus derived naive T-cells is a feature of HIV infection. Here the impact of HIV infection on the compartmentalization of recent thymic emigrants of (RTE) and naive T-cells was examined. METHODS: Peripheral blood mononuclear cells (PBMC) and lymphoid tissue (LT) from 43 HIV-infected patients and 12 controls were examined for RTE distribution by measuring coding joint T-cell receptor excisional circles (cjTREC) by PCR and naive and memory T-cell subsets and adhesion molecules (L-selection, LFA-1) by flow cytometry. RESULTS: In HIV-infected patients, the RTE as quantified by cjTRECs in CD4 LT cells were significantly higher than in PBMC. Their values, however, were less than in control subjects, in both the LT and PBMC compartments. This was associated with an increase in L-selectin and LFA-1 expression on LT derived T cells. In PBMC, a significant positive relationship between TREC and naive CD4 cells and an inverse relationship between TREC and cellular viral load (CVL) was observed. Whereas in LT, there was a positive relationship between cjTREC and both naive CD4 cell percentage and CVL. CONCLUSIONS: Collectively, the data suggests that LT is a significant reservoir for RTE. The RTE appeared to be entrapped in LT from HIV-infected subjects. Such entrapment is probably a response to the high viral load in these tissues. These observations may partially explain the decline in RTE observed in the peripheral blood of HIV-infected patients, and the delay in recovery of naive cells in blood after initiation of HAART.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Lymphoid Tissue/immunology , Thymus Gland/immunology , Adult , CD4 Lymphocyte Count , Female , Flow Cytometry , Humans , L-Selectin/metabolism , Lymphocyte Function-Associated Antigen-1/metabolism , Male , Middle Aged , RNA, Viral/metabolism , Receptors, Antigen, T-Cell/metabolism , Viral LoadABSTRACT
Cytomegalovirus (CMV) disease is a common complication of patients with advanced human immunodeficiency virus infection. The aim of the present study, based on a case-cohort design, was to determine the predictive value of follow-up and baseline qualitative plasma CMV polymerase chain reaction (PCR) values for CMV end-organ disease in 378 patients (158 who progressed to CMV end-organ disease and 220 who did not develop CMV disease). These patients are part of the full AIDS Clinical Trials Group 204 multinational study (1227 patients), a randomized, controlled trial that compared the effects of valacyclovir with those of acyclovir for CMV disease prevention. Baseline PCR positivity was a significant risk factor for CMV disease progression (relative risk [RR], 1.81; 95% confidence interval [CI], 1.09-3.00). In multivariate analyses, time-updated PCR positivity was strongly associated with progression to CMV end-organ disease (RR, 4.42; 95% CI, 2.87-6.81). Change in cumulative PCR status was informative for the risk of subsequent CMV disease.
