Session 68
Antiretroviral Therapy in Treatment-Naïve Patients

• Poster 510: Preliminary Results of a Randomized Multicenter Study Comparing Combivir (ZDV/3TC) plus Nelfinavir or Nevirapine in HIV-Infected Naive Patients (COMBINE Study) (Authored by D. Podzamczer, E. Ferrer, E. Consiglio, J.M. Gatell, J. Perez, J.L. Perez, L. Lozano, A. Gonzalez, R. Sole, C. Azuaje, J.M. Libre, A. Gonzalez, A. Casiro, M. Aranda, P. Barrufet, J.M. Lacasa, X. Badia, P. Cahn, and S. Lupo. Spain and Argentina)
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• Poster 515: ABT-378/ritonavir (ABT-378/r) in Antiretroviral-Naïve HIV-Positive Patients: 72 Weeks (Authored by R. Gulick, M. King, S. Brun, K. Real, R. Murphy, C. Hicks, J. Eron, J. Thommes, M. Thompson, C. White, C. Benson, M. Albrecht, H. Kessler, A. Hsu, R. Bertz, D. Kempf, E. Sun, and A. Japour for the M97-720 Study Group. Cornell; Northwestern; Duke; Univ. of North Carolina; Pacific Oaks Res.; AIDS Res. Consortium of Atlanta; Baylor; Univ. of Colorado; Harvard; Rush; and Abbott Labs)
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• Poster 518: A Pilot Study of FTC + ddI + Efavirenz in Treatment-Naïve HIV-Infected Adult: A Potent and Convenient Once-a-Day HAART (ANRS 091 Trial) (Authored by J.M. Molina, F. Ferchal, C. Rancinan, F. Raffi, W. Rozenbaum, D. Sereni, P. Morlat, V. Journot, J.M. Decazes, and G. Chene. Hosp. of Paris, Nantes, Bordeaux, and ANRS, France)
  Click here to view the original abstract

Thirteen posters were presented which reviewed trials of HAART in people with no prior therapy (treatment-naïve). A few of the most important ones are reviewed below.

Poster 510: Preliminary Results of a Randomized Multicenter Study Comparing Combivir (ZDV/3TC) plus Nelfinavir or Nevirapine in HIV-Infected Naive Patients (COMBINE Study)

This was one of the more provocative of the treatment-naïve posters. Researchers from Spain and Argentina compared a regimen of zidovudine (ZDV) and 3TC (Epivir); plus either nevirapine (Viramune), a NNRTI; or nelfinavir (Viracept, 1,250 mg twice a day), a protease inhibitor. The people had an average HIV RNA of 100,000 before therapy, and an average of 347 T-helper (CD4) cells.

After six months, the people treated with the NNRTI (nevirapine) had better virologic suppression to HIV RNA <200, 74% versus 60%, when all patients who began the study were examined. If one looked only at the patients who did not drop out of the study, either due to side effects, or other reasons, the nevirapine group had 91% with HIV RNA <200, versus 82% for the nelfinavir group. Like prior studies, which compared another NNRTI, efavirenz (Sustiva), to a protease inhibitor, indinavir (Crixivan), this study confirms the potential equivalency, or even superiority, of an NNRTI, compared to a protease inhibitor, in people without prior therapy. There is some concern that in people with high viral loads, i.e., those who have viral loads above 100,000, an NNRTI might not provide as good viral suppression, but this poster did not report on the results based on baseline HIV RNA. (Although no differences were seen in the studies of Sustiva of the high versus low HIV RNA groups.)

Poster 515: ABT-378/ritonavir (ABT-378/r) in Antiretroviral-Naive HIV-Positive Patients: 72 Weeks

Trip Gulick, from Cornell in New York, reported results of a dosing trial of ABT-378, a new HIV protease inhibitor. ABT-378 contains a small amount of ritonavir which provides for high levels of ABT-3787 in the blood, providing a potentially very high pharmacologic barrier to drug resistance.

Two groups of antiretroviral-naïve patients received d4T/3TC with a randomly assigned, blinded ABT-378/ritonavir dose: 200/100 mg (Group I), or 400/100 mg (Group II), twice a day. At week 48, 83%-86% of patients on treatment had viral load <50 copies/ml. After 72 weeks, 25/27 patients (93%) on treatment in Group I, and 45/45 patients (100%) had HIV RNA <400 copies/ml. All doses have been well tolerated to date, with only one discontinuation for adverse events related to ABT-378/r through 72 weeks. As other studies have reported though, even low doses of ritonavir cause elevations in cholesterol and triglycerides. Certainly, ABT-378 is a potent protease inhibitor, and whether it will be used as first line, or second line therapy remains to be seen.

Poster 518: A Pilot Study of FTC + ddI + Efavirenz in Treatment-Naive HIV-Infected Adult: A Potent and Convenient Once-a-Day HAART (ANRS 091 Trial)

A study from France reported on a 24-week trial of the above once-a-day regimen, which included a new NRTI, FTC, in 40 people. This was a 24-week pilot study in 40 antiretroviral-naïve HIV-1 infected adults. Eligible patients had to have a CD4 cell count of >100/mm³ and a plasma HIV-RNA >5000 copies/ml at baseline. All three drugs were taken once a day, at bedtime: FTC (200 mg), ddI (400 mg if >60 kg; 250 mg if >60Kg) and EFZ (Sustiva) (600 mg). At week 12, of all patients who started treatment (39/40) had a viral load below 400 copies/ml, and 20/40 (50%) had a viral load less than 20 copies/ml. The average increase in CD4 count at week 12 was 120 cells/mm³. At week 24, a sustained decrease in viral load was noted, with 24/28 patients achieving <20 copies/ml. 24 patients (60%) experienced transient central nervous system adverse events, and only 3 (7.5%) experienced a rash. Mild diarrhea was also reported in 10 patients (25%). This preliminary report showed that FTC+ddI+EFV is a potent and well tolerated once-a-day HAART regimen that will worthwhile to study further.