Combined analysis of two-year follow-up from two open-label randomized trials comparing efficacy of three nucleoside reverse transcriptase inhibitor backbones for previously untreated HIV-1 infection: OzCombo 1 and 2.
OBJECTIVE
To compare inhibition of HIV replication, improvements in CD4+ T-cell counts, metabolic parameters, and body shape changes after 2 years of assigned therapy in OzCombo patients.


METHODS
Study participants were those who were recruited into the open-label OzCombo 1 (1996/1997) and OzCombo 2 (1997/1998) trials. Patients in OzCombo 1 were randomized to receive indinavir in combination with zidovudine+lamivudine (AZT+3TC; n = 35), stavudine (d4T)+3TC (n = 34), or d4T+didanosine (ddI) (n = 37). OzCombo 2 patients were randomized to the same nucleoside reverse transcriptase inhibitor (NRTI) backbones with nevirapine (n = 20, 22, 23, respectively). The mean time-weighted changes from baseline in CD4 T-cell count/mL, HIV RNA (log copies/mL plasma), and proportions with detectable viral load (<500 copies plasma HIV RNA/mL) between NRTI arms over 2 years were compared by formal meta-analysis. A cross-sectional study of metabolic and body shape complications was also undertaken.


RESULTS
For the comparison of d4T+3TC and d4T+ddI to AZT+3TC, mean differences in time-weighted change from baseline in CD4 T-cell count/microL and log copies HIV RNA/mL adjusted for baseline CD4+ T-cell and HIV RNA counts were: -44 (p =.08) and -14 (p =.56) cells/microL and -0.1 (p =.40) and -0.1 (p =.6) copies/mL. Odds ratios for detectable viral load in the last study quarter were 0.6 (p =.44) and 1.0 (p =.95). The mean percent leg fat was lower in the d4T+3TC and d4T+ddI than the AZT+3TC arm (mean difference 5.1% [p =.07] and 7.6% [p =.02], respectively).


CONCLUSIONS
For all regimens, virological control and immunological response were maintained over 2 years. Regimens containing d4T and particularly d4T+ddI were significantly associated with increased peripheral fat loss compared with AZT+3TC.
Amin
J
J
National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia. Jamin@nchecr.unsw.edu.au
Moore
A
A
Carr
A
A
French
M A
MA
Law
M
M
Emery
S
S
Cooper
D A
DA
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D010349:Patient Compliance; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D019380:Anti-HIV Agents; D012367:RNA, Viral