Lopinavir/ritonavir (LPV/r) remains a key drug for therapy of pediatric HIV and proved efficacious as an infant prophylaxis in the ANRS 12274 trial. However, reports of growth retardation in LPV/r vs. Nevirapine based combinations in HIV-infected children prompt the need to assess whether this drug could impact infant growth during the first year of life.
In the ANRS 12174 trial, implemented in 4 African countries, 1273 HIV-uninfected breastfed children born from HIV-infected mothers were randomized at 7 days for either lamivudine or LPV/r until the end of breastfeeding (max 50 weeks) as pre-exposure prophylaxis. Each month, weight and height were measured using standardized high-quality assessments. For these analyses, children were censored when they stopped the study drugs or when they became infected with HIV (N=19). Z-scores were calculated and compared between arms using the least mean squares method at 26 and 50 weeks, linear mixed models and spline regression models.
Overall, 1266 children were included in the analyses, who accumulated 12443 visits. While the length for age score was not different between arms, the weight for age (WHA) score was consistently lower in the LPV/r arm than in the 3TC arm: difference of -0.18 (95%CI: -0.30;-0.5, p=0.006) at 26 weeks, and of -0.24 (95%CI : -0.44 ;-0.05, p=0.02) at 50 weeks. The weight for height (WHZ) score was similarly lower in the LPV/r arm, with differences of -0.22 (95%CI: -0.34;-0.09, p<0.001) at 26 weeks, and of -0.25 (95%CI: -0.46 ;-0.03, p=0.02) at 50 weeks. For both WHA and WHZ, the reduction over time was confirmed by linear mixed model (p=0.02 and p<0.001, respectively), while spline regression models suggest that this reduction occurs early and remain constant thereafter (p=0.02 with knot at 118 days for WHA, and p<0.001 with knot at 44 days for WHZ). Interestingly, the impact of LPV/r was much higher in girls than in boys, and in Burkina Faso and Uganda than in Zambia and South Africa.
This large randomized trial comparing LPV/r vs. 3TC administration in exposed-uninfected children provided a unique opportunity to evaluate the impact of LPV/r on growth. LPV/r initiated at 7 days of life induced a lower weight gain among HIV-uninfected children. These findings have implications for the early treatment of HIV-infected children and for further choice of prophylactic regimen.