A randomized, dose-finding study with didanosine plus stavudine versus didanosine alone in antiviral-naive, HIV-infected Thai patients.
OBJECTIVE
To evaluate the safety and efficacy of four different regimens of didanosine (ddI) + stavudine (d4T) in HIV-infected Thais.


METHODS
Prospective, open-label, randomized study.


METHODS
Patients were randomized to four regimens of high and low doses of ddI and d4T or to ddI alone. D4T was added to the ddI-alone arm after week 24. The duration of study was 48 weeks.


RESULTS
Seventy-eight patients were randomized (mean CD4 cell count, 255 x 10(6)/l; mean plasma HIV-1 RNA; 4.3 log10 copies/ml). In the intent-to-treat analysis, 78% of patients in the pooled combination arms and 20% of the patients in the ddI alone arm (to which d4T was added after 24 weeks) showed plasma HIV-1 RNA < 500 copies/ml at week 24 (P < 0.001), and 59% versus 53% at week 48, respectively. In addition, the proportion of patients with < 50 HIV-1 RNA copies/ml was 13% versus 7% at week 24 (P = 0.5) and 17% versus 20% at week 48 respectively. At week 24, median CD4 cell count increases from baseline were 101 x 10(6)/l in the pooled combination versus 76 x 10(6)/l in the ddI alone arm (P = 0.78). Logistic regression modeling suggested a correlation between receiving high dose ddI and achieving HIV-1 RNA < 500 copies/ml at week 48 (P = 0.07).


CONCLUSIONS
The d4T/ddI combination was superior to ddI alone in producing HIV-1 viral suppression. At week 48, > 60% of patients treated with this combination reached HIV-1 RNA levels < 500 copies/ml. Receiving high dose ddI but not d4T may correlate with a better viral suppression.
Ruxrungtham
K
K
Thai Red Cross AIDS Research Centre, the Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok.
Kroon
E D
ED
Ungsedhapand
C
C
Teeratakulpisarn
S
S
Ubolyam
S
S
Buranapraditkun
S
S
van Leeuwen
R
R
Weverling
G J
GJ
Kunanusont
C
C
Lange
J M
JM
Cooper
D A
DA
Phanuphak
P
P
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012449:Safety; D018119:Stavudine / Q000008:administration & dosage* / Q000009:adverse effects; D013785:Thailand
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018119:Stavudine; D016049:Didanosine