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Background:  A randomized clinical trial of ART-naïve subjects with HIV-1 infection was conducted to compare structured interrupted therapy and continuous therapy in terms of immunologic and virologic outcomes, severity of side-effects, and cost of therapy.

Methods:  Adult patients with CD4 counts of 50 to 350 cells/mm³, and plasma viral load of > 5000 copies/mL within 6 weeks of study entry were enrolled and placed on Indian-manufactured (CIPLA) generic HAART:  efavirenz (EFV) + zidovudine (AZT)/stavudine (d4T) + lamivudine (3TC). After 6 months of continuous therapy, subjects were randomized to structured treatment interruption (STI) of a week-on, a week-off cycle, or continuous therapy. Those who did not achieve a plasma viral load of < 400 or CD4 > 300 at the end of 6 months of continuous therapy were not randomized and were placed into a clinic comparison group. Primary end-point was the proportion of subjects maintaining CD4 > 200 at 12 months after randomization; secondary end-points were plasma viral load suppression, adverse effects, and cost. All analyses were done for intention-to-treat populations.

Results:  Of 40 patients enrolled in the study, 25 patients (64% men, median age 40), 13 on STI and 12 on continuous therapy, were followed for at least 12 months, 6 months pre- and 6 months post-randomization. Data from these 25 patients are reported here. Median baseline CD4 for STI and continuous therapy was 137 [IQR:  84 to 273] and 200 [IQR:  144 to 232], respectively (p = 0.65). Baseline median plasma viral load was 310,500 [IQR:  124,500 to 715,500] for STI and 203,500 [IQR:  107,000 to 732,250] for continuous therapy (p = 0.47). Median CD4 for STI just prior to randomization was 378 [IQR:  341to 463] and 365 [IQR:  327 to 396] for continuous therapy (p = 0.23). In both groups, 100% of patients had a plasma viral load of < 400. There was no significant difference between the 2 groups, 6 months post-randomization, median CD4 was 498 [IQR:  449 to 548] for STI and 416 [IQR:  375 to 426] for continuous therapy. For SIT and continuous therapy, 100% of patient had CD4 > 200 and all 13 patients on STI had a plasma viral load < 400. However, 1 patient on STI had 3 detectable plasma viral loads in the interim. Of 12 patients on continuous therapy, 11 had a plasma viral load of < 400. There were no serious adverse events or deaths. There was no difference in lipid profiles between the 2 groups. Cost of therapy of STI was less than half that of continuous therapy.

Conclusions:  STI was effective at maintaining CD4 above 200 cells/mm³ and successfully suppressing plasma viral load in all patients. Adverse events were comparable in both groups. Cost to patients would be lower with STI regimen. Though longer follow-up is needed, these results suggest that STI might be as effective as continuous therapy and is an option for patients in resource-constrained settings.

Keywords: Structured Interrupted Therapy; Generic HAART; Resource Limited Settings