|Authors: Heaton R, Franklin D, Ellis R, Letendre S, LeBlanc S, Woods S, Clifford D,Rivera Mindt M, Taylor M, Marcotte T, Atkinson JH, Collier A, Marra C, Gelman B, McArthur J, Morgello S,Simpson D, McCutchan JA, Grant I
for the CHARTER and HNRC Groups|
|Abstract:Introduction: Combination antiretroviral therapy (CART) has greatly reduced the incidence of opportunistic infections as well as mortality in HIV-infected individuals, but studies of its effect on the prevalence of NCI have been mixed. This study examined the prevalence of NCI in the pre- and post-CART eras in persons at various stages of HIV infection.
Methods: 857 individuals (HIV-, n=179; non-AIDS, n=516; AIDS, n=162) from the pre-CART era (1990-1995) were compared to 937 individuals (HIV-, n=94; non-AIDS, n=336; AIDS, n=506) from the post-CART era (2000-2007) on the basis of having received comparable comprehensive neuromedical and neuropsychological (NP) evaluations; participants were also selected to have similar exclusion criteria for non-HIV CNS comobidities. NP analyses employed age-education-gender-ethnicity adjusted scores.
Results: Overall, 40% of HIV-infected individuals had NCI in the post-CART era vs. 33% of HIV-infected individuals in the pre-CART era (p=.004). Analysis by CDC Stages showed significantly higher NCI in CDC A only (36% post-CART vs 25% pre-CART, p =.001).There was no difference in NCI in HIV- controls between eras (post-CART = 16% vs pre-CART = 19%) or in people with more advanced HIV disease (CDC B: 40% post-CART vs 42% pre-CART; CDC C: 48% post-CART vs 52% pre-CART). Post-CART individuals were more likely to be on ARVs (70% vs. 47%; p<.0001) and more likely to have an undetectable plasma viral load (65% vs. 5%; p<.0001). The estimated duration of infection was longer in post-CART than pre-CART (9.9 vs 2.8 yrs, p < .0001). The effect of duration of infection was only significant pre-CART (NCI = 3.4 yrs vs NP-normal = 2.5 yrs; p=.0005)
Conclusions: NCI remains prevalent despite CART. Of interest, more post-CART non-AIDS cases have NCI than pre-CART. This suggests the negative CNS effects of longer survival in a pre-AIDS state during which the brain remains exposed to repeated fluxes in HIV and/or chronic immune stimulation.|