Neurocognitive Function at the First-Line Failure and on the Second-Line Antiretroviral Therapy in Africa

Abstract

Objective: To assess neurocognitive function at the first-line antiretroviral therapy failure and change on the second-line therapy. Design: Randomized controlled trial was conducted in 5 sub-Saharan African countries. Methods: Patients failing the first-line therapy according to WHO criteria after .12 months on non-nucleoside reverse transcriptase inhibitors-based regimens were randomized to the second-line therapy (open-label) with lopinavir/ritonavir (400 mg/100 mg twice daily) plus either 2–3 clinician-selected nucleoside reverse transcriptase inhibitors, raltegravir, or as monotherapy after 12-week induction with raltegra vir. Neurocognitive function was tested at baseline, weeks 48 and 96 using color trails tests 1 and 2, and the Grooved Pegboard test. Test results were converted to an average of the 3 individual test z-scores. Results: A total of 1036 patients (90% of those .18 years enrolled at 13 evaluable sites) had valid baseline tests (58% women, median: 38 years, viral load: 65,000 copies per milliliter, CD4 count: 73 cells per cubic millimeter). Mean (SD) baseline z-score was 22.96 (1.74); lower baseline z-scores were independently associated with older age, lower body weight, higher viral load, lower hemoglobin, less education, fewer weekly working hours, previous central nervous system disease, and taking fluconazole (P , 0.05 in multivariable model). Z-score was increased by mean (SE) of +1.23 (0.04) after 96 weeks on the second-line therapy (P , 0.001; n = 915 evaluable), with no evidence of difference between the treatment arms (P = 0.35). Conclusions: Patients in sub-Saharan Africa failing the first-line therapy had low neurocognitive function test scores, but performance improved on the second-line therapy. Regimens with more central nervous system-penetrating drugs did not enhance neurocognitive recovery indicating this need not be a primary consideration in choosing a second-line regimen.

Description

Keywords

Neurocognitive function, Antiretroviral therapy, Failure, Second line, Africa, Trial

Citation

Kambugu, A., Thompson, J., Hakim, J., Tumukunde, D., van Oosterhout, J.J., Mwebaze, R., Hoppe, A., Abach, J., Kwobah, C., Arenas-Pinto, A. and Walker, S.A., 2016. Neurocognitive function at the first-line failure and on the second-line antiretroviral therapy in Africa: analyses from the EARNEST trial. JAIDS Journal of Acquired Immune Deficiency Syndromes, 71(5), pp.506-513.