Reports on advances in antiretroviral therapy played a prominent role at the Vancouver Conference. Throughout the week, optimism was generated by the developments of the past year. As discussed in the opening plenary session, this progress includes proof of the clinical benefit of combination therapy, a demonstrated survival benefit from treatment of asymptomatic patients with CD4 counts between 200 - 500/mm3, the development of new agents, the beginning of the protease-inhibitor era, and the benefits of treating primary infection. Selected studies highlighting these developments are described here.
Combinations of Nucleoside Reverse Transcriptase Inhibitors:
NUCA 3001/3002: AZT/3TC was compared to AZT or 3TC monotherapy in
AZT-naive patients and to AZT/ddC in AZT-experienced patients. Patients on
AZT/3TC had greater declines in viral RNA and greater increases in CD4 counts
than other groups. In addition, a clinical benefit to AZT/3TC combination
therapy was demonstrated. This is the first report of a clinical benefit from
Combinations Including Non-Nucleoside Reverse Transcriptase Inhibitors :
INCAS Trial: Combinations of AZT, ddI, and nevirapine were evaluated
in antiretroviral-naive, asymptomatic patients with CD4 counts 200 - 600/mm3.
Triple therapy (AZT/ddI/nevirapine) had a greater effect on viral RNA and CD4
count than either AZT/ddI or AZT/nevirapine: 60% of patients on the triple
combination had undetectable viral RNA (<200 copies/ml) at 1 year.
Rash was common: 7 of 98 patients taking nevirapine had to discontinue therapy because of this side effect. (Note: nevirapine was approved by the FDA in June and should only be used as part of combination therapy with nucleoside analogs.)
Ongoing Delavirdine Trials:
Pharmacia and Upjohn Protocol 0021: Dose-ranging combinations of
delavirdine (200, 300, or 400 mg bid) and AZT were compared to AZT monotherapy
in patients with CD4 counts of 200 - 500/mm3. On delavirdine doses of 300 - 400
mg bid (in combination with AZT), CD4 counts showed a sustained increase of
20-30/mm3 (35-70 cells higher than AZT monotherapy), and viral load remained
suppressed by .5 -.6 log at 60 weeks. Rashes occurred frequently but rarely led
to medication discontinuation.
Combinations Including Protease Inhibitors:
NV14256: AZT-experienced patients with CD4 counts of 50 - 300/mm3
received ddC, saquinavir, or the combination of these agents. The combination
reduced the risk of disease progression or death by 53% and the risk of death by
72% compared with ddC alone. (There were no differences between the two
Therapy in Early Infection: Dr. Martin Markowitz presented information on 12 patients with early (within 90 days of seroconversion) HIV infection who were treated with AZT, 3TC, and ritonavir. Of the eight patients who have continued therapy (for up to 10 months to date), HIV RNA is undetectable, and cultures for HIV are negative. The CD4/CD8 ratio has normalized in all these patients, and CD4 counts have increased by about 200 cells.
This article was provided by Johns Hopkins AIDS Service. It is a part of the publication Hopkins HIV Report.