Six-year follow-up of HIV-1-infected adults in a clinical trial of antiretroviral therapy with indinavir, zidovudine, and lamivudine.
OBJECTIVE
To assess virological and immunological responses and toxicity in subjects receiving combination antiretroviral therapy.


METHODS
Six-year follow-up of a single arm of a randomized study of combination antiretroviral therapy.


METHODS
HIV-infected, zidovudine-experienced patients originally randomized to receive indinavir, zidovudine, and lamivudine had HIV RNA levels and CD4 cell counts assessed over 6 years. Information was collected by questionnaire from subjects who discontinued the study regimen before 6 years. Both on-study and post-study responses were assessed.


RESULTS
Of 33 subjects, 16 (48%) discontinued before 6 years of follow-up. After 6 years, 16 (53%) and 14 (47%) of 30 contributing subjects had HIV RNA levels < 500 and < 50 copies/ml, respectively, and the median increase in CD4 cell count from baseline for 28 contributing subjects was 268 x 10(6) cells/l. Treatment-limiting nephrolithiasis occurred in four subjects. Of the 16 subjects who discontinued the study, 12 had post-study questionnaire data available and seven had HIV RNA < 500 copies/ml on a post-study regimen. In an exploratory analysis combining both on-study and post-study data at approximately 6 years, 26 (79%) and 19 (58%) of 33 had HIV RNA levels < 500 and < 50 copies/ml, respectively, and the median increase in CD4 cell count from baseline was 344 x 106 cells/l.


CONCLUSIONS
Antiretroviral therapy with indinavir, zidovudine, and lamivudine suppressed HIV viremia and produced continued CD4 cell increases in a majority of subjects for 6 years. Most subjects who discontinued study medications had HIV RNA levels suppressed on post-study therapy. Though based on a small group, this study demonstrates the durable effects of antiretroviral therapy.
Gulick
Roy M
RM
Weill Medical College of Cornell University, New York, USA.
Meibohm
Anne
A
Havlir
Diane
D
Eron
Joseph J
JJ
Mosley
Audrey
A
Chodakewitz
Jeffrey A
JA
Isaacs
Robin
R
Gonzalez
Charles
C
McMahon
Deborah
D
Richman
Douglas D
DD
Robertson
Michael
M
Mellors
John W
JW
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir