Prevalence and Outcomes of Recycling NNRTIs Despite Documented NNRTI Resistance in HIV-Infected Children and Youth

Abstract

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly used in pediatric patients; however, rapid development of resistance, due to non-adherence and cross-resistance, results in their discontinuation and limits their recycling. We evaluated the clinical experience of recycling NNRTIs despite documented NNRTI resistance (NNRTI-R), and examined virologic and CD4 cell count outcomes among participants enrolled in Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY), a national HIV-infected pediatric cohort. We conducted a retrospective analysis of LEGACY participants with major NNRTI-R. Using chisquare analyses and logistic regression, we examined demographic and clinical factors associated with prescription of NNRTIs despite documented NNRTI-R, and associated changes in plasma HIV RNA viral load and CD4 cell counts. Sixteen of 133 (12%) participants with documented NNRTI-R re-started NNRTIs for a median of 370 days (IQR 105-919) with a median 402 days (IQR 70-841) between documentation of NNRTI-R to NNRTI recycling. Participants recycling NNRTIs were less likely to have documented past non-adherence (40.0% vs. 69.2%; p = 0.02). Among twelve patients with virologic data at 24 ( -8) weeks; seven (58.3%) experienced virologic suppression while on the recycled NNRTI-based regimens. Of the five who failed to suppress, three with subsequent genotyping developed additional NNRTI-R mutations compromising higher generation NNRTIs. While NNRTI's were recycled in only a small fraction of LEGACY participants harboring NNRTI-R mutations, such recycling increased the risk of inducing further resistance mutations that compromised use of higher generation NNRTIs.

Perspectives and Practice of HIV Disclosure to Children and Adolescents by Health-Care Providers and Caregivers in sub-Saharan Africa: A Systematic Review

“…All studies in the final selection included various types of studies ranging from 13 qualitative study design, including interviews and focus groups ( 23 , 24 , 27 , 28 , 30 – 32 , 34 – 36 , 39 , 40 ), to 4 quantitative study design ( 21 , 26 , 33 , 37 ) and 2 mixed methods design ( 25 , 38 ). The 19 articles included studies conducted in 10 SSA countries.…”

“…Most studies utilized small samples, with the largest four studies including 40 HCPs ( 34 ), 394 caregivers ( 26 ), and 858 children and adolescents ( 38 ). Three studies included only HCPs ( 32 , 34 , 40 ), and five studies included only caregivers ( 29 – 31 , 37 , 39 ). One study included both HCPs and community members with focus on HIV disclosure and discussions about grief ( 21 ).…”

“…One study included both HCPs and community members with focus on HIV disclosure and discussions about grief ( 21 ). The three studies that included only HCPs-provided information on types of disclosure in practice and the most suitable person and setting to disclose ( 32 , 34 , 40 ). Some of the studies included caregivers living with HIV and others without HIV.…”

“…Two studies among caregivers in South Africa and Uganda reported high preference for the parent or caregiver to disclose rather than HCPs ( 29 , 30 ). A study in Uganda and Kenya indicated that HCPs support caregivers when they initiate disclosure ( 27 , 32 ), but adolescents preferred HCPs to disclose rather than their caregivers because they had an opportunity for more accurate information about their disease ( 27 ). A study in South Africa indicated that caregivers preferred that the HCP or family members, especially the paternal aunt and grandmother disclose rather than the mother ( 21 ).…”

“…A study in South Africa indicated that caregivers preferred that the HCP or family members, especially the paternal aunt and grandmother disclose rather than the mother ( 21 ). Although some caregivers preferred to disclose to infected children themselves, they expressed fears of competence in disclosure; acceptance by the child; stigma from accidental disclosure by the child to others; and need for support ( 29 , 31 , 32 , 34 , 39 ).…”