Los Angeles, Calif. – Investigators from the AIDS Clinical Trials Group (ACTG), the world’s
largest and longest-established HIV research network, today announced that the Journal of
Clinical Investigation published new findings from the ACTG HIV Reservoirs Cohort Study
(A5321). The study found that HIV DNA remained in the cerebrospinal fluid of half of
participants with well-managed HIV (virologic suppression in the plasma), confirming that the
central nervous system (CNS) is a major reservoir for latent HIV. Individuals who harbored HIV
DNA in the cerebrospinal fluid were more likely than other study participants to experience
cognitive deficits on neurocognitive testing.
“The persistence of HIV in sanctuary sites in the human body, even in the presence of long-term
therapy, is a challenge to HIV remission and cure that the ACTG is actively working to address,”
said ACTG Chair Judith Currier, M.D., MSc, University of California Los Angeles. “Because
neurocognitive function can be compromised even in individuals whose HIV is well treated, it is
very important that we understand HIV persistence in the CNS so that we can develop
strategies to treat it. This study provides preliminary insights into these challenges.”
This substudy in the ACTG HIV Reservoirs Cohort Study (A5321) was led by Serena Spudich,
M.D., Yale University, the late Kevin Robertson, Ph.D., University of North Carolina at Chapel
Hill, and John Mellors, M.D., University of Pittsburgh. The study included 69 participants with
well-treated HIV who had their cerebrospinal fluid and blood collected and underwent
neurocognitive assessments, which included tests of memory, learning, motor function, and
more. Participants were mostly male (97 percent) and had been on HIV treatment for a median
of almost nine years, with a good response to medications (HIV viral loads in the plasma were
all <100 copies/mL and median CD4 counts were in the normal range). Using highly sensitive
methods to detect HIV, researchers found that almost half of these participants harbored viral
DNA in cells found in the cerebrospinal fluid. Of those, 30 percent met the criteria for cognitive
impairment.
While the study established an association between HIV DNA in cerebrospinal fluid with poorer
performance on cognitive tests, researchers stressed that it did not establish a causal
relationship, noting that there could be several explanations for the findings. Further studies will
help determine strategies to reverse this persistence and improve neurological functioning in
individuals with long-standing HIV.