HIV Treatment Reduces but Does Not Abolish CNS Inflammation in Past Substance Users

Antiretroviral therapy (ART) reduced systemic and central nervous system (CNS) inflammation in past substance users compared with nonusers, according to the results of an 80-person comparison presented at IDWeek 2016. But after ART began, CNS inflammation remained significantly higher in past substance users than in people who never used harmful substances.

Yale University researchers and collaborators who conducted this study noted that substance use and HIV infection are interlinked epidemics and that drugs of abuse foster a proinflammatory environment in the CNS. But how substance use affects CNS inflammation and neurocognitive impairment over time in people with HIV remained unknown until this study.

To address these issues, the researchers recruited men infected with HIV within 12 months of enrollment and still naive to ART. Participants began ART during the study period. The investigators divided these men into three groups: no history of substance use, occasional use (fewer than two to three times monthly) and dependent use (more than two to three times monthly for more than one year). The researchers gauged CNS inflammation by measuring neopterin in cerebrospinal fluid (CSF) and plasma, and participants completed neuropsychological testing in five domains. The investigators calculated neuropsychological test results as total z score, which is normalized for age and education. Measurements were made at a baseline visit, after six weeks, then every six months for up to four years.

The study had 80 male participants: 16 nonusers, 24 occasional users and 40 dependent users. Marijuana and methamphetamine were the most popular drugs among dependent users. The groups did not differ significantly in age (around 36 years), education (around 15 years) or baseline CD4 count, plasma viral load or CSF viral load.

Mixed-model analysis determined that, compared with nonuse, a history of dependent substance use was associated with higher pre-ART baseline levels of plasma neopterin (β = +7.2, P = .041) and CSF neopterin (β = +6.9, P = .027). These results mean that dependent substance use was associated with a 7.2-unit higher plasma neopterin and a 6.9-unit higher CSF neopterin. Starting ART attenuated these associations, but the analysis still found a trend toward an association between dependent substance use and plasma neopterin (β = +3.6, P = .094) and a significant association with CSF neopterin (β = +4.3, P = .022).

Analysis of neuropsychological test results determined that a history of substance dependence, compared with nonuse, was not associated with neurocognitive impairment at the pre-ART baseline (β = -0.19, P = .24) but was associated with declining neurocognitive performance after ART began (β = -0.58, P = .008).

The Yale team concluded that a substance dependence history is associated with greater pre-ART CNS inflammation and with ongoing inflammation after ART begins. Despite effective ART, past substance use was linked to worse neuropsychological test results. The researchers recommended actively considering drug use history when interpreting HIV-related CNS research.