Lipid Profiles in Young HIV-Infected Children Initiating and Changing Antiretroviral Therapy

Abstract

Background Both HIV infection and antiretroviral therapy are associated with dyslipidemias in adults but there are fewer data on outcomes in young children. Here we examined lipid profile changes in a cohort of young children before and after suppression on an initial ritonavir-boosted lopinavir (LPV/r)-based regimen and after switch to a nevirapine (NVP)-based regimen. Methods 195 HIV-infected children who initiated LPV/r-based therapy when <24 months of age at one site in Johannesburg, South Africa, and who achieved viral suppression (<400copies/ml sustained for ≥ 3 months) were randomised to either continue on the LPV/r-based regimen (n=99) or to switch to a NVP-based regimen (n=96). Non-fasting concentrations of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TG) were measured pre-treatment, at randomization when suppressed, and at 9, 20 and 31 months post-randomization. Results Median age at treatment initiation was 9 months and the initial regimen was maintained for an average of 9 months before randomization. TC, LDL and HDL increased from pre-treatment to randomization (p<0.0001) and TC/HDL ratio and TG decreased (p<0.0001). After switching to NVP, HDL was significantly higher (p<0.02) and TC/HDL and TG significantly lower (p<0.0001) through 31 months post-switch relative to remaining on the LPV/r-based regimen. Conclusion Initiating antiretroviral therapy was associated with changes to a more favorable lipid profile in young children. Switching from a LPV/r-based regimen to a NVP-based regimen accentuated and continued these improvements. Investigation of safe and effective methods for managing dyslipidemias in children of different ages in resource-limited settings is warranted.

Endocrinopathies in Children Infected with Human Immunodeficiency Virus

“…Atazanavir has a more favorable lipid profile and a switch to atazanavir has been shown to reduce lipid levels in children. 93 Strehalau and colleagues 88 reported that with initiation of a lopinavir/ ritonavir-based regimen, children infected with HIV had increases in HDL, LDL, and total cholesterol, and decreases in total cholesterol/HDL ratio and triglyceride (TG) levels, a pattern that corresponds with prior descriptions. After switching to nevirapine, HDL was significantly higher and total cholesterol/HDL ratio and TG significantly lower compared with the group remaining on the PI-based regimen.…”

Association of Dyslipidemia and Glucose Abnormalities With Antiretroviral Treatment in a Cohort of HIV-Infected Latin American Children

“…The cumulative incidence results support the need for further investigation into the cause of these rather high rates of lipid abnormalities. In a clinical trial in South Africa, Strehlau et al, found that initiation of PI-based regimens resulted in significant increases in total cholesterol, LDL and HDL cholesterol and decreases in the total cholesterol: HDL ratio and TG [19]. To our knowledge, the largest longitudinal study that examined the association of PIs and other ART with lipid levels in HIV-infected children was the study of Tassiopoulos et al In contrast to our findings, this study, which focused only on hypercholesterolemia because fasting was not required, concluded that PI-based (boosted and nonboosted) regimens and use of NNRTIs were significant risk factors for hypercholesterolemia.…”

Nevirapine- Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy in HIV-Infected Infants and Young Children: Long-term Follow-up of the IMPAACT P1060 Randomized Trial

“…For consistency with prior publications on shorter-term outcomes, we used this protocol-defined composite outcome. While the primary focus of this trial was HIV-related outcomes, studies have shown unfavorable alterations in lipid profiles and body composition among infants on LPV/r [27,28]. Longitudinal data on such outcomes are needed as, with current treatment recommendations, the duration of LPV/rbased ART exposure will only increase for perinatally infected children.…”