A randomized, double-blind trial of half versus standard dose of zidovudine plus zalcitabine in Thai HIV-1-infected patients (study HIV-NAT 001)

Background: Triple combination antiretroviral therapy, recommended as stand ard of care, is unaffordable for much of the developing world. Objectives: To establish whether half doses of zidovudine (AZT) and zalcita bine (ddC) are as effective as standard doses in a Thai population with low er body weight than Western populations and predominantly infected with HIV -1 subtype E. Methods: A group of 116 antiretroviral naive patients, with CD4 cell counts 100-500 x 10(6) cells/l, were randomized to: AZT 200 mg three times daily plus ddC 0.75 mg three times daily versus AZT 100 mg three times daily plus ddC 0.375 mg three times daily and followed-up regularly for 48 weeks. Results: The study enrolled 111 patients: 59 men and 52 women, body weight (mean +/- standard deviation) 56.4 +/- 12.3 kg, mean CD4 cell count 324 X 1 0(6) cells/l, mean HIV RNA 4.7 log(10) copies/ml. There were no significant differences between the two groups. Twelve patients discontinued, includin g two deaths that were unrelated to study medication. No significant differ ences in adverse events were seen. Week 48 data for the standard dose and h alf dose arms, respectively, were mean CD4 cell count increases of 52 and 7 8 x 10(6) cells/l (P = 0.34), mean plasma HIV-1 RNA reduction of 1.4 and 1. 1 log(10) copies/ml (P = 0.10), HIV RNA of < 400 copies/ml in 52 and 20% (P = 0.001). Participants with higher than mean baseline CD8 cell counts (mea n 1062 x 10(6) cells/l) showed greater decline in CD8 cells on standard dos es. Further analysis showed improved reduction in HIV RNA (P < 0.0001) and in the percentage with undetectable HIV RNA (P = 0.0137) in the standard do se arm, corrected for baseline HIV RNA, which if < 4.75 log(10) copies/ml s ignificantly correlated with HIV RNA < 400 copies/ml at week 48.