Table 3.

Randomized trials evaluating first-line regimens for HIV-infected infants and young children

Study	Location	Cohort	Randomization	Endpoints	Main Results
P1060 [69,70]	South Africa, Zimbabwe, Zambia, Malawi, Uganda, Tanzania, India	Cohort 1: N=164, previously exposed to sd-NVP	Randomized to A) nevirapine, zidovudine, lamivudine or B) LPV/r, zidovudine, lamivudine	Primary endpoint: treatment failure (permanent discontinuation of treatment, death, toxic effects, virological failure)	Cohort 1: more children in the nevirapine group reached the primary endpoint of treatment failure at 24 weeks than the LPV/r group (39.6% versus 21.7%, p=0.02)
		Cohort 2: N=288, not previously exposed to sd-NVP
		Age: 6-36 months in Cohort 1; 2-36 months in Cohort 2			Cohort 2: more children in the NVP group reached the primary endpoint of treatment failure at 24 weeks than the LPV/r group (40.1% versus 18.6% p<0.001)
PENPACT-1 [71]	North and South America and Europe	N=266	Factorial design, randomized to A) PI-based regimen or B) NNRTI-based regimen as well as to a viral load threshold to switch regimen at 1,000 or 30,000 cpm	Primary endpoint: change in log10 HIV-1 RNA viral load between baseline and 4 years	No significant difference was found between children starting NNRTI- or PI-based regimens in primary or secondary endpoints
		Age: 0.1 to 17.8 years, median 6.5 years		Secondary endpoints: regimen switch, change in CD4% from baseline, viral load <400 cpm at week 24 on first-line ART, viral load <400 cpm at 4 years, continued viral load suppression on first-line ART, failure of second-line ART, grade 3/4 adverse events, new CDC stage C events and resistance
ARROW [75]	Uganda, Zimbabwe	N=1206	Factorial design, randomized to A) three drugs - NNRTI, lamivudine, abacavir; B) four drugs - NNRTI, lamivudine, abacavir, zidovudine for 36 weeks then NNRTI, lamivudine, abacavir; or C) four drugs - NNRTI, lamivudine, abacavir, zidovudine for 36 weeks then lamivudine, abacavir, zidovudine, as well as to different monitoring strategies	Primary endpoint: new WHO stage 4 events or death for monitoring and change in CD4% at 72 and 144 weeks	Mean CD4% change did not differ between ART groups at 72 weeks (16.5% vs. 17.1% vs. 17.3%, p=0.33) or 144 weeks (p=0.69).
		Age: 3 months to 17 years		Co-primary toxicity endpoint: grade 3 or 4 adverse events	Four-drug groups (B, C) were superior to three-drug group A at 36 weeks (12.4% vs. 14.1% vs. 14.6%, p<0.0001).
					There were excess grade 3 or 4 events in groups B (hazard ratio 1.32, 95% CI: 1.07-1.63) and C (hazard ratio 1.58, 95% CI: 1.29-1.94) compared to A.

Abbreviations: PI = protease inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; LPV/r = ritonavir-boosted lopinavir