Virological response and resistances over 12 months among HIV‐infected children less than two years receiving first‐line lopinavir/ritonavir‐based antiretroviral therapy in Cote d’Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort

Abstract

Introduction: Lopinavir/ritonavir-based antiretroviral therapy (ART) is recommended for all HIV-infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12-month response to lopinavir/ritonavir-based antiretroviral therapy in a cohort of West African children treated before the age of two years.Methods: HIV-1-infected, ART-naive except for a prevention of mother-to-child transmission (PMTCT), tuberculosis-free, and less than two years of age children with parent’s consent were enrolled in a 12-month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed.Results: Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8–18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow-up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed-up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09–6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03–7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05–6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation.Conclusions: Twelve-month VS rate on lopinavir/ritonavir-based ART was high, comparable to those in Africa or high-income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy-to-identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.

High Levels of Dual-Class Drug Resistance in HIV-Infected Children Failing First-Line Antiretroviral Therapy in Southern Ethiopia

“…Our findings starkly contrast the only other report of drug resistance among children failing first-line cART in Ethiopia, undertaken on specimens collected from 13 participants only three years following cART rollout, where only one child harbored HIV-1 drug resistance [ 41 ]. Our findings are comparable to rates of overall drug resistance reported in pediatric first-line treatment failure in other African nations including Cote d’Ivoire and Burkina Faso (75%) [ 38 ], Mali (73%) [ 37 ] and slightly lower than those reported in Cameroon (90%) [ 39 ]. Dual-class resistance was most commonly observed in our cohort (69%), an observation consistent with reports from settings where similar pediatric first-line regimens are currently used (e.g., Mali and Cameroon) [ 37 , 39 , 94 , 95 ].…”

“…As a result, regimens are often changed without knowledge of HIV-1 drug resistance [ 27 , 28 ] and the contribution of drug resistance to treatment failure in these settings remains incompletely understood. Although studies of HIV-infected adults failing first-line cART in Africa [ 29 , 30 , 31 , 32 ], Asia [ 33 , 34 ] and Central America [ 35 ], as well as a meta-analysis across multiple global sites [ 36 ], suggest resistance mutation burden is substantial in these populations, studies investigating the burden of drug resistance among children failing first-line cART in resource limited-settings are scarcer [ 37 , 38 , 39 , 40 ], thus limiting our knowledge in this area.…”

Long-term virological outcome in children receiving first-line antiretroviral therapy

“…Various predictors of VF have been identified and reported in the literature, which include younger age [ 30 ], low CD4% at the time of ART initiation [ 30 ], type of ART [ 26 , 30 ], baseline NNRTI resistance [ 26 , 28 ], etc. Father as the main caregiver of the child and lack of access to tap water; have also been identified as risk factors for VF [ 32 ]. Njom et al [ 33 ] reported that being motherless children (motherless orphanhood) was associated with VF (aOR: 2.9, 95% CI 1.3–6.1).…”

Analytical performance of four molecular platforms used for HIV-1, HBV and HCV viral load determinations

“…In viral hepatitis, baseline and ontreatment VLs help guide therapeutic decisions [2,[9][10][11]. In the HIV-1-infected patient on combination antiretroviral therapy, a detectable VL signifies active viral replication and can trigger one of several possible interventions [12][13][14][15][16][17][18][19].…”