A randomized study of the safety and antiretroviral activity of hydroxyurea combined with didanosine in persons infected with human immunodeficiency virus type 1. American Foundation for AIDS Research Community-Based Clinical Trials Network.

This randomized open-label trial of human immunodeficiency virus type 1-infected persons compared safety and efficacy for 38 patients receiving hydroxyurea/didanosine combination therapy with findings in 42 persons given didanosine monotherapy for 12 weeks, followed by 12 weeks of hydroxyurea/didanosine combination therapy for all patients. Week 12 on-treatment group comparisons showed a mean decrease in virus load between hydroxyurea/didanosine versus didanosine groups of -0.93 versus -0.74 log10 copies/mL (P=.20); a higher percentage of the hydroxyurea/didanosine group below the assay's detection limit (500 copies/mL), 29% versus 7% (P=.017); and median change in CD4 cells for the hydroxyurea/didanosine versus didanosine group of 0 versus 43 cells/mm3 (P=.045), although median change in CD4 percentage was similar (0.9% vs. 1.2%, P=.64). Week 24 virus load reductions and CD4 cell changes were similar in both groups. Intent-to-treat and on-treatment analyses showed similar results. The hydroxyurea/didanosine combination was well tolerated.

Efficacy of nelfinavir in patients switched from ritonavir/saquinavir combination antiretroviral therapy.

UNLABELLED: Based on available data and expert opinion, the IAS-USA treatment guidelines recommend "selective substitution" of the medication thought most likely to be causing a side effect for one that should have a different side effect profile. PURPOSE: This study evaluates the short-term virological efficacy of selective substitution with nelfinavir-nucleoside combination therapy in individuals with plasma viral RNA below 400 copies/mL. METHOD: This study involved a retrospective chart review at five large urban HIV Clinical practice settings and included 19 patients taking combination therapy including ritonavir with saquinavir. We performed selective substitution with a nelfinavir combination. Our main outcome measure was plasma HIV-1 RNA (Amplicor) obtained during the period between weeks 12 to 18. RESULTS: We identified 19 HIV-1-infected individuals with evidence of viral suppression as defined by a viral load below 400 copies/mL while taking dual nucleoside reverse transcriptase inhibitors with ritonavir/saquinavir. Reasons for switching included adverse effects (37%) or preference for nelfinavir due to the possibility of a better defined salvage regimen (63%). We defined a composite viral endpoint indicative of continued viral suppression using the first 12 to 18 weeks following the medication change. We found that 73% maintained undetectable viral loads (plasma HIV RNA below 400 copies/mL) during this period. CONCLUSION: These data suggest that any medication adjustment should be made cautiously, as there may be some potential risk in a substitution. Selective substitution of a medication that has undesirable side effects or other characteristics should be considered when the possible risks of the loss of viral suppression are outweighed by the potential benefits of that substitution.

Lack of effect of cimetidine on lymphocyte subsets in patients infected with human immunodeficiency virus type 1.

Cimetidine, widely used for peptic ulcer disease, blocks type 2 histamine receptors present on immune cells, including T cells, B cells, and monocytes. As an earlier published study showed evidence of increases in CD4 cell counts due to this drug, we conducted a randomized, placebo-controlled, 8-week trial of oral cimetidine (400 mg p.o. t.i.d.) in a study involving 182 patients infected with human immunodeficiency virus (HIV). Overall, cimetidine-treated patients had a decline in CD4+ cell counts that was no different from the decline for placebo-treated persons, neither during the first 8 weeks of the trial (mean drop, 7.1% [standard error, 12.1-1.8] vs. 6.7% [standard error, 11.6-1.5]) nor during the subsequent 8 weeks of open-label administration of cimetidine. No differences were evident between the treatment groups in terms of the percentage reactive to p24 antigen at baseline, and p24 antigen concentrations did not change from baseline to the end of week 8. In summary, cimetidine is well tolerated by HIV-infected individuals but alters neither CD4+ cell counts nor at least one quantitative measure of viral load, HIV p24 antigen levels.