AEGiS-12IAC: Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:13 (abstract no. 11156)

De Wolf F, Weverling GJ, Lukashov VV, Prins G, Jurriaans S, Goudsmit J, Lange JM
Dept. of Human Retrovirology, AMC, Univ. Amsterdam, The Netherlands.

BACKGROUND: 3-drug regimens with 2 nucleoside analogue HIV-RT inhibitors and 1 protease inhibitor has rapidly become standard of care for the treatment of HIV-infection. However, it is unlikely that this combination treatment exerts enough drug pressure on every single infected cell and thus may be limited in its anti-HIV efficacy. Effect after 84 days on HIV-RNA plasma levels of a 4 and a 5-drug regimen was compared to that of a 3-drug regimen.

MATERIAL AND METHODS: HIV-RNA plasma levels in 15 anti-HIV drug naïve patients on triple (ZDV + 3TC + RIT), 35 on quadruple (d4T + 3TC + NLV + SAQ) and 8 plus 1 experienced patient on quintuple (ZDV + 3TC + 1592U89 + NEV + IND) treatment, were determined using NucliSens (Organon Teknika, The Netherlands) with a lower detection limit of 50 copies/mL. A non-linear regression function was fitted for each patient by using the formula Vt = Cexp(-Bt)+A, where Vt represents log₁₀HIV-RNA c/ml at time t, C a constant, B the decline function (like the slope of decline in a linear regression), t the time (days) since the start of anti-HIV treatment and A an asymptote or the RNA level that would be reached if the number of days were infinite. Kaplan-Meier analysis was done for the time to RNA level < 500 and < 50 c/ml.

RESULTS: Time to < 500, as well as < 50 HIV-RNA c/ml was significantly shorter with the 5-drug regimen than the other two regimens (p = 0.04 and 0.003). The decline function (B) was 0.078 for the 3 and 0.068 for the 4-drug regimen. The 5-drug regimen showed the strongest decline (0. 152; p = 0.025). A higher asymptote (A) was found for the 3-drug regimen and for the 4 and 5-drug regimens A was less than 50 copies/ml. B did not differ between those with baseline HIV-RNA > 105 or < 105 c/ml, but A was significantly (p = 0.04) lower for the group with RNA < 105.

CONCLUSIONS: 1) Treatment with the 5-drug regimen led to a more rapid decline of serum HIV-RNA levels than treatment with the standard 3 and the 4-drug regimen; 2) The eventual level of viral suppression achieved with the 3-drug regimen appeared to be less good compared to the 5 and 4-drug regimen; 3) The baseline viral load affects the level of viral suppression eventually achieved.

Keywords: AEGIS, HIV-1, Zidovudine, Lamivudine, HIV Infections, Virus Replication, Dideoxynucleosides, Viral Load, Stavudine, Antiretroviral Therapy, Highly Active, HIV-1 Reverse Transcriptase, Drug Therapy, Combination, Netherlands, abacavir, Human, virology, therapy, drug therapy, ICA12
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