Six months of d4T lead-in followed by AZT reduced anemia and enhanced CD4 count restoration in a 72-week randomized trial comparing d4T switched to AZT vs. AZT vs. TDF with 3TC or FTC and NVP in ART-naive Thais
Background: Due to superior long-term toxicity profile, AZT and TDF are preferred to d4T for first-line regimens. However, short-term d4T use could be beneficial in avoiding AZT-induced anemia.
Methods: Naive Thai HIV-infected adults were randomized (1:1:1) to arm1: 24-wk d4T30mg+3TC150mg+NVP200mg followed by 48-wk AZT250mg+3TC150mg+NVP200mg; arm2: 72-wk AZT250mg+3TC150mg+NVP200mg; or arm3: 72-wk TDF300mg+FTC200mg+NVP. During NVP lead-in, AZT was given at 200mg or 300mg BID for weight< 60kg or >60kg, respectively. Neuropathic signs, hemoglobin, creatinine, CD4, HIV-RNA, DEXA, and adherence were assessed.
Results: Among 150 randomized patients, 55% were female, mean (SD) age was 34.5 (7.8) years. Baseline mean CD4 was 161 (94) cells/mm3, HIV-RNA was log104.87 (0.65) copies/ml, hemoglobin was 12.5 (1.6) g/dL, weight was 58 (11) kg, and eGFR (MDRD formula) was 83 (16) ml/min/1.73m2.
From baseline-wk24, mean hemoglobin in arm2 decreased compared to arm1 (-0.19 vs. 0.68 g/dL, p=0.001) but changes in peripheral fat or neuropathic signs were similar among arms. At wk72, mean hemoglobin in arm3 increased compared to arm1 (0.90 vs. 0.17, p=0.006) while changes were similar between arms1&2. Arm1 had less peripheral neuropathic signs than arm2 (10% vs. 29%, p=0.02) but larger decrease in peripheral fat than arm3 (-358 vs. 399 g, p=0.04). Changes in eGFR, lean body mass, and weight were similar among arms.
CD4 increased more in arm1 than arms2&3 from baseline-wk24 (168 vs. 117 and 118 cells/mm3, p=0.01 and 0.02) but was similar among arms by wk 72. Changes in HIV-RNA and adherence were similar among arms.
Conclusions: Short-term d4T use before introducing AZT caused less anemia and peripheral neuropathic signs compared to initiating treatment with AZT. Initial rise in CD4 was greatest with d4T. However, peripheral fat reduction by DEXA could be observed at 1 year after d4T discontinuation. A 6-month d4T lead-in therapy could be considered in patients with anemia or low baseline CD4.
N. Phanuphak1,2, J. Ananworanich1,3,4, N. Teeratakulpisarn2, T. Jadwattanakul5, S.J. Kerr6, J.L.K. Fletcher1, N. Chomchey1, P. Hongchookiat2, P. Mathajittiphun5, P. Rungrojrat1, P. Praihirunyakit1, M. Gerschenson4, P. Phanuphak1,2,3, V. Valcour7, J.H. Kim8, C. Shikuma4, on behalf of the SEARCH 003 Study Group
1South East Asia Research Collaboration with Hawaii, Bangkok, Thailand, 2The Thai Red Cross AIDS Research Centre, Bangkok, Thailand, 3Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 4University of Hawaii at Manoa, Honolulu, United States, 5Queen Savang Vadhana Memorial Hospital, Chonburi, Thailand, 6HIV Netherlands Australia Thailand Research Collaboration, Bangkok, Thailand, 7University of California - San Francisco, San Francisco, United States, 8US Military HIV Research Program, Rockville, Thailand