Comparative potency of three antiretroviral therapy regimes in primary HIV infection.

BACKGROUND: Virally mediated destruction of HIV-specific CD4+ T-cells in primary HIV infection (PHI) may be abrogated by potent antiretroviral therapy (ART) started in acute infection. To best achieve the most rapid reduction in primary viraemia we compared three different ART regimens in PHI. STUDY DESIGN AND METHODS: A sequential, unblinded, non-randomized prospective cohort study. The primary endpoint was time to achieve plasma viral load (pVL) < 50 copies HIV RNA/ml. One hundred and five patients identified with PHI according to the definition: HIV antibody negative with positive HIV DNA (n = 22), HIV antibody positive with a documented negative test within the previous 6 months (n = 53), low-level incident 'detuned' assay (n = 10) or an evolving HIV-antibody test (n = 20) were recruited. Ninety of 105 individuals chose to take a short course of ART at PHI whereas 15 of 105 declined therapy. Seventy-nine of 90 were included for analysis and were allocated sequentially to either three (29 of 79) or four-drug (33 of 79) or protease inhibitor-containing ART (17 of 79). RESULTS: A mathematical model-based analysis of viral decay indicated significantly faster viral load decline in patients receiving the four-drug regimen (P = 0.01). This conclusion was supported by a non-significant on-treatment analysis of the time taken to reach pVL <50 copies HIV RNA/ml (P = 0.07) but not by the corresponding intend-to-treat analysis. This discordance was caused by greater toxicities associated with the four-drug regimen, although the differences were not significant. CONCLUSION: Of the three treatment regimens compared, the four-drug arm enhanced the rate of decline of primary viraemia but at the cost of toxicity.

CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater.

OBJECTIVE: CD4 cell count changes in therapy-naive patients were investigated during 7 years of highly active antiretroviral therapy (HAART) in an observational cohort. METHODS: Three endpoints were studied: (1) time to >or=800 CD4 cells/mm in 5299 therapy-naive patients starting HAART, (2) CD4 cell count changes during 7 years of uninterrupted HAART in a subset of 544 patients, and (3) reaching a plateau in CD4 cell restoration after 5 years of HAART in 366 virologically suppressed patients. RESULTS: Among patients with <50, 50 to 200, 200 to 350, 350 to 500, and >or=500 CD4 cells/mm at baseline, respectively, 20%, 26%, 46%, 73%, and 87% reached >or=800 CD4 cells/mm within 7 years of starting HAART. Periods with HIV RNA levels >500 copies/mL and age >or=50 years were associated with lesser increases in CD4 cell counts between 6 months and 7 years. Having reached >or=800 CD4 cells/mm at 5 years, age >or=50 years, and >or=1 HIV RNA measurement >1000 copies/mL between 5 and 7 years were associated with a plateau in CD4 cell restoration. CONCLUSIONS: Restoration to CD4 cell counts >or=800 cells/mm is feasible within 7 years of HAART in most HIV-infected patients starting with >or=350 cells/mm and achieving sufficient suppression of viral replication. Particularly in patients >or=50 years of age, it may be beneficial to start earlier than current guidelines recommend.

The effect on treatment comparisons of different measurement frequencies in human immunodeficiency virus observational databases.

Data collected in a routine clinical setting are frequently used to compare antiretroviral treatments for human immunodeficiency virus (HIV). Differences in the frequency of measurement of HIV RNA levels and CD4-positive T-lymphocyte cell counts introduce a possible source of bias into estimates of the difference in effectiveness between treatments. The authors investigated the size of this bias when survival analysis methods are used to compare the initial efficacy of antiretroviral regimens. Data sets of clinical markers were simulated by use of differential equations that model the interaction between HIV and human T-cells. Cox proportional hazards and parametric models were fitted to the simulated data sets to evaluate the bias and coverage of 95% confidence intervals for the difference between regimens. The authors' results demonstrate that differences in the frequency of follow-up can substantially bias estimated treatment differences if methods do not correctly account for the intervals between measurements and if the statistical model chosen does not fit the data well. Analyses using methods applicable to interval-censored data reduce the bias. In the Athena cohort of HIV-infected individuals in the Netherlands from 1999 to 2003, there are differences in measurement frequency between current regimens that are of sufficient magnitude to conclude incorrectly that some regimens are more effective than others.