ART reduces neurocognitive impairment risk

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Initiating antiretroviral therapy (ART) may reduce the risk for neurocognitive impairment in patients living with HIV, according to study results.

The study included participants from the AIDS Clinical Trials Group (ACTG) 5199 (International Neurological Study [INS]). Participants were from 7 resource-limited countries and HIV-positive. Participants in the study were ART-naïve with CD4+ cell counts <300 and were randomly assigned to start 1 of 3 World Health Organisation-recommend first-line ART regimens.

The researchers applied normative data from the International Neuro-cognitive Normative Study (INNS) to INS. INNS included normative comparison data on high-risk HIV-negative participants from 10 voluntary counselling and testing sites. The researchers used generalised estimating equations to estimate associations.

Of the 860 HIV+ participants from ACTG 5199, 55% had no neuro-cognitive impairment at baseline, 25% had mild neuro-cognitive impairment, 17% had moderate impairment, and 3% had severe impairment.

After ART initiation, the rate of neuro-cognitive impairment dropped substantially, with 37% of participants impaired at week 24, 36% at week 48, 31% at week 72, 27% at week 96, 26% at week 120, 29% at week 144, 26% at week 168, and 20% at week 192.

ART also decreased the rates of moderate and severe impairment, with the number of participants with moderate impairment decreased to 6% and participants with severe impairment decreased to 0.6% at week 168.

The researchers calculated that the initiation of ART reduced the estimated odds of neuro-cognitive impairment by 12% for every 24 weeks on ART (P <.0001).

“These improvements in neuro-cognitive performance would likely lead to sustained improvements in productivity and quality of life in those living with HIV in (resource limited settings),” the researchers wrote.

Background: Neurocognitive impairment remains a common complication of HIV despite effective antiretroviral therapy (ART). We previously reported improved neurocognitive functioning with ART initiation in seven resource limited settings (RLS) countries for HIV+ participants from AIDS Clinical Trials Group (ACTG) 5199 (International Neurological Study (INS)). Here we apply normative data from the International Neurocognitive Normative Study (INNS) to INS, to provide previously unknown rates of neurocognitive impairment.
Methods: A5199, INS assessed neurocognitive and neurological performance within a randomized clinical trial with 3 arms, containing WHO first line recommended ART regimens (ACTG 5175; PEARLS). ACTG 5271, INNS collected normative comparison data on 2400 high-risk HIV negatives from 10 voluntary counseling and testing (VCT) sites aligned with INS. Normative comparison data were used to create impairment ratings for HIV+ participants in INS; associations were estimated using generalized estimating equations.
Results: Among 860 HIV+ adults enrolled in ACTG 5199, 55% had no neurocognitive impairment at baseline. Mild neurocognitive impairment was found in 25%, moderate in 17% and severe in 3% of participants. With the initiation of ART, the estimated odds of impairment was reduced 12% (95% CI: 9%, 14%) for every 24 weeks (p<.0001) on ART. Mild impairment dropped slightly, and then remained at about 18% out to week 168.
Conclusions: Almost half of HIV+ participants had neurocognitive impairment at baseline before ART, based on local norms. With ART initiation, there were significant overall reductions in neurocognitive impairment over time, especially in those with moderate and severe impairments.

Kevin R Robertson, Hongyu Jiang, Johnstone Kumwenda, Khuanchai Supparatpinyo, Christina M Marra, Baiba Berzins, James Hakim, Ned Sacktor, Thomas B Campbell, Jeff Schouten, Katie Mollan, Srikanth Tripathy, Nagalingeswaran Kumarasamy, Alberto La Rosa, Breno Santos, Marcus T Silva, Cecilia Kanyama, Cindy Firhnhaber, Robert Murphy, Colin Hall, Cheryl Marcus, Linda Naini, Reena Masih, Mina C Hosseinipour, Rosie Mngqibisa, Sharlaa Badal-Faesen, Sarah Yosief, Alyssa Vecchio, Apsara Nair

Infectious Disease Advisor material
Clinical Infectious Diseases Journal abstract

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