Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV

Abstract

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18–24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n=56); group 2 had CD4 >350 and were not initiating ART (n=66); group 3 initiated ART with CD4 <350 (n=59) per standard of care treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

Attention/Working Memory, Learning and Memory in Adult Cameroonians: Normative Data, Effects of HIV Infection and Viral Genotype

“…Our data showing no effect of ART or current CD4 T-cells levels on attention/WM, learning, or memory agree with other studies showing that HAND persists in the ART era, with no major effect of VL, ART use, or current CD4 T-cells levels on cognitive function. In fact, a 3-year longitudinal study of young adults starting ART found no major effect of ART on attention/WM, learning, or memory (Nichols et al, 2016). A recent 4-year longitudinal study of PLWH on ART and virologically suppressed found that NCI persisted and there were no significant differences in the proportion with NCI at baseline and at 4-years (K. Robertson et al, 2019).…”

Soluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living with HIV from healthy controls

“…CD4 T cell counts > 350 cells/μl who remained untreated until CD4 counts declined to <350 cells/μl; and 3. CD4 T cell counts <350 cells/μl who initiated ART at entry [16]. Plasma viral levels, CD4 counts, diagnoses, and medications were abstracted from clinic records at study visits.…”

“…YLWH were enrolled in the Adolescent Trials Network (ATN) for HIV/AIDS Interventions protocol 071/101, Assessment of Inflammatory Markers Associated with Neurocognitive Impairment in HIV-infected Adolescents , a sub-study of ATN 071, Neurocognitive Assessment in Youth Initiating ART , a 3-year longitudinal study, initiated in April 2008 with the last participant completing the study in 2013 (ClinicalTrials.gov Identifier NCT00683579) [16]. Enrollment was at 22 sites throughout the United States and Puerto Rico; procedures included routine monitoring of clinical HIV disease, neurocognitive assessments and self-reported substance use[16]. A single blood sample to assess biomarkers was obtained at week 144.…”

“…Identifier NCT00683579). 16 Enrollment was at 22 sites throughout the United States and Puerto Rico; procedures included routine monitoring of clinical HIV disease, neurocognitive assessments, and selfreported substance use. 16 A single blood sample to assess biomarkers cell counts < 350 cells/𝜇L who initiated ART at entry.…”

HIV Associated Neurocognitive Disorders Subsidence Through Citalopram Addition in Anti-retroviral Therapy (HANDS-CARE): A Concept Note

“…Some reports have also suggested that up to a quarter of PLWHA experience new neurocognitive impairments after initiation of HAART ( 26 ). Second, it remains unclear whether the use of antiretroviral agents with higher CPE scores confer actual and unique advantages or whether early introduction of HAART benefit HAND prospectively in the medium to longer term ( 27 ). Given these limitations, it would appear that HAART alone is an inadequate intervention for HAND.…”