Human Immunodeficiency Virus Type 1 and Tuberculosis Coinfection in Multinational, Resource-limited Settings: Increased Neurological Dysfunction

Abstract

Background: AIDS Clinical Trial Group 5199 compared neurological and neuropsychological test performance of human immunodeficiency virus type 1 (HIV-1)-infected participants in resource-limited settings treated with 3 World Health Organization-recommended antiretroviral (ART) regimens. We investigated the impact of tuberculosis (TB) on neurological and neuropsychological outcomes.

Methods: Standardized neurological and neuropsychological examinations were administered every 24 weeks. Generalized estimating equation models assessed the association between TB and neurological/neuropsychological performance.

Results: Characteristics of the 860 participants at baseline were as follows: 53% female, 49% African; median age, 34 years; CD4 count, 173 cells/μL; and plasma HIV-1 RNA, 5.0 log copies/mL. At baseline, there were 36 cases of pulmonary, 9 cases of extrapulmonary, and 1 case of central nervous system (CNS) TB. Over the 192 weeks of follow-up, there were 55 observations of pulmonary TB in 52 persons, 26 observations of extrapulmonary TB in 25 persons, and 3 observations of CNS TB in 2 persons. Prevalence of TB decreased with ART initiation and follow-up. Those with TB coinfection had significantly poorer performance on grooved pegboard (P < .001) and fingertapping nondominant hand (P < .01). TB was associated with diffuse CNS disease (P < .05). Furthermore, those with TB had 9.27 times (P < .001) higher odds of reporting decreased quality of life, and had 8.02 times (P = .0005) higher odds of loss of productivity.

Conclusions: TB coinfection was associated with poorer neuropsychological functioning, particularly the fine motor skills, and had a substantial impact on functional ability and quality of life.

Clinical trials registration: NCT00096824.

Keywords: HIV; cognitive impairment; neuropsychological functioning; resource-limited; tuberculosis.

Figure 1.

Prevalence plot for TB before and after antiretroviral therapy (ART): the proportion of extrapulmonary TB to all cases of TB over weeks on study. The prevalence of TB dropped with the initiation of ART. Abbreviation: TB, tuberculosis.

Figure 2.

Estimated 95% confidence interval for association with grooved pedboard: poorer grooved pegboard with current tuberculosis for both dominant and nondominant hands, while baseline tuberculosis was significantly slower only for the nondominant hand. Other covariates in each GEE model include country, treatment arm, screening HIV-1 RNA strata, screening CD4 count, baseline neurologic function, age, sex years of education, and week. Abbreviations: GEE, generalized estimating equations; HIV-1, human immunodeficiency virus type 1; TB, tuberculosis.

Figure 3.

Estimated 95% confidence interval for odds ratio association between tuberculosis (TB) and neurological outcomes: diffuse central nervous system disease, usually associated with human immunodeficiency virus-associated neurocognitive disorders, was increased in those with current TB. Abbreviations: GEE, generalized estimating equations; MCMD, Minor Cognitive Motor Disorder.