Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

SURVIVAL IN ZDV-EXPERIENCED PATIENTS: COMBINATION ANTIRETROVIRAL THERAPY VS. DDI/DDC MONOTHERAPY VS. CONTINUED ZDV MONOTHERAPY.

Graham NMH, Saah AJ, Park LP, Mellors JW, Detels R, Phair JP.
Multicenter AIDS Cohort Study (MACS), USA.

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 7.4
AIDS 1994, Vol. 8 (Suppl. 4);S6

PURPOSE: To determine, among men who start zidovudine with intermediate stage HIV infection, whether changing to combination antiretroviral therapy (CART), to other monotherapy with DDI or DDC 10MTI or continuing with zidovudine (ZMT) have differential effects on AIDS-free time and survival.

METHOD: 853 HIV seropositive men in the (MACS) a large observational cohort of gay or bisexual men) started ZDV prior to an AIDS-defining illness (mean CD4= 310 cell/μ. Men were seen semiannually with a median follow-up time of 2.7 years (Range 0.25-5.5 years) from 1987-1993. Intent-to- treat Cox proportional hazards models were used to compare risk of AIDS n = 334) and death n = 280) among men who changed from ZMT to CART (ZDV and DDI or DDC), to OMT (DDI or DDC) or who stayed on ZMT. Treatment groups (CART, OMT, ZMT) were modelled as time. dependent variables, as were important prognostic variables including CD4 count, platelets, hemoglobin, HIV symptoms, PCP prophylaxis and acyclovir use. Intent-to-treat paradigm assumes that once treatment is initiated in each group it remains constant for the remainder of follow-up. Time-dependent modelling of treatment group and other covariates adjusts for length of follow-up, eliminates survival bias, and minimizes disease stage selection bias.

RESULTS: Under the intent-to-treat paradigm, with continued ZMT as the reference group land controlling for all other time. dependent covariates above) no benefit for AIDS-free time was seen for those who changed to OMT (RR=1.05; p0.631. The group who changed to CART were 23% less likely to develop AIDS (RR=0.771 but this was not statistically significant p = 0.1 0). With survival as the outcome, compared to continuing ZMT, those who changed to OMT did no better (RR=1.03; p0.86). However, the survival advantage for those who changed to CART was 34% (RR=0.66; p0.007). Less conservative on-treatment time-dependent Cox models were also run and gave similar results.

CONCLUSIONS: For men with intermediate stage HIV infection who are zidovudine experienced, adding DDI or DDC as CART was associated with significantly better survival than switching to OMT with DDI or DDC or continuing with zidovudine monotherapy. Definitive clinical trials of CART are urgently needed in intermediate and early HIV infection to assess efficacy and toxicity.

Presenting author: Graham NMH

1994-11-18
7.4

Originally published in AIDS Volume 8, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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