Oral Abstract Submission
Understanding drug resistance in perinatally HIV-infected children (PHIC) when viral load (VL) monitoring is limited is critical for life-long antiretroviral use. Resistance data in PHIC in sub-Saharan Africa are limited. Though guidelines recommend PI-based 1st-line regimens in PHIC, many worldwide remain on NNRTI-based regimens. We examined treatment failure, resistance and outcomes in Kenyan PHIC on 1st-line NNRTI-based therapy.
PHIC were enrolled in 2010-13 at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, a large program caring for > 160,000 HIV patients; > 15,000 PHIC. VL testing, not routinely available then, was done for all, and resistance testing was done in viremic PHIC. Clinical data were derived from medical records. Subtype and resistance interpretation were with Stanford Database tools. Associations between failure ( > 1000 copies/mL) or resistance, and demographic, clinical or lab variables were evaluated with Fisher Exact and Wilcoxon Rank Sum tests.
Of 482 PHIC enrolled, 52% were female, median age 8.4 years (range 1-15), median CD4% 28 (range 0-53), 79% on zidovudine (AZT)/abacavir (ABC)+lamivudine(3TC)+efavirenz (EFV)/nevirapine (NVP) for median 2.3 years. Treatment failure was seen in 31%, associated with low CD4% and count. Genotypes were available in 124, 47% female, median age 8.3 years (range 2-15), median CD4% 22 (range 0-45), 81% on AZT/ABC+3TC+EFV/NVP for median 2.5 years, median VL 7,515 copies/mL. Subtypes were A-76%, C-3%, D-15%, recombinants-6%. Reverse transcriptase mutations were in 93%; 93%-NNRTIs, median 2/patient, most common Y181C (44%); 89%-NRTIs, median 3/patient, most common M184V (85%); 89%-dual class, median 5/patient. Intermediate-high resistance to potential 2nd-line drugs included 62%-etravirine, 66%-rilpivirine and 19%-tenofovir. Of 92/124 (74%) PHIC with follow-up data, 27% remained on NNRTI-based 1st-line (median CD4 count 461), of who 24% had suppressed VL and 48% died; and 73% switched to PI-based 2nd-line (median CD4 count 591), of who 72% had suppressed VL and 6% died (P < 0.05 for both).
PHIC in western Kenya on NNRTI-based 1st-line regimens had high treatment failure rates and extensive drug resistance with poor clinical outcomes, demanding urgent interventions.