Virologically suppressed patients with asymptomatic and symptomatic HIV-associated neurocognitive disorders do not display the same pattern of immune activation.

OBJECTIVES: Inversion of the CD4:CD8 ratio is a marker of immune activation and age-associated disease. We measured the CD4:CD8 ratio as a marker of cognitive impairment in HIV-infected patients and explored differences according to clinical severity. METHODS: Post hoc analysis of data from two prospective cohorts of HIV-infected patients randomly selected to undergo neuropsychological tests was performed. Test scores were adjusted for age, gender and education. Inclusion criteria were undetectable viral load and stable treatment for at least 6 months. Subjects with HIV-associated dementia were excluded. Patients were divided into an unimpaired group, a group with asymptomatic neurocognitive disorder (ANI) and a group with symptomatic HIV-associated neurocognitive disorder (sHAND), represented by mild neurocognitive disorder (MND). Demographic and background parameters, immune activation markers and the CD4:CD8 ratio were recorded. RESULTS: Two hundred patients were included in the study. The mean age was 52 years, 78% were male, the mean CD4 count was 624 cells/µL, the mean nadir CD4 count was 240 cells/µL, 27% were hepatitis C virus (HCV)-coinfected, the mean duration of HIV infection was 16 years, and the mean time on current combination antiretroviral therapy (cART) was 2.9 years. Twenty-nine per cent of subjects had HAND (21% had ANI and 8% had MND). In multivariate analysis, a CD4:CD8 ratio < 1 was associated with a nadir CD4 count < 200 cells/µL [odds ratio (OR) 3.68] and with the presence of CD4(+) CD38(+) HLA(+) cells (OR 1.23). Multinominal logistic regression showed that, in comparison with the unimpaired group, diagnosis of sHAND was associated with a CD4:CD8 ratio < 1 (OR 10.62), longer HIV infection (OR 1.15) and longer current cART (OR 1.34), while the ANI group differed from the unimpaired group only for education level. CONCLUSIONS: Aviraemic patients with sHAND did not display the same pattern of immune activation as subjects with ANI, suggesting that the underlying pathophysiological mechanisms could be different.

[Causes and characteristics of death among HIV-1 infected patients with immunovirologic response to antiretroviral treatment]. / Causes et caractéristiques des décès des patients infectés par le VIH-1, en succès immuno-virologique sous traitement antirétroviral.

INTRODUCTION: To analyse the causes of death among HIV-infected adults in France in the year 2000. METHODS: Based on data from a national survey, our study describes and analyses the causes and characteristics of patients with immunological and virological response (CD4>200/mm3, ARN-HIV<500 copies/mL), who died during antiretroviral treatment. RESULTS: Among a total of 964 deaths registered, data on 864 cases were available for analysis. One hundred forty-nine patients (17%)were immunovirological responders. The underlying causes of death were non AIDS-defining malignancies for 36 (24%), mainly due to lung cancer (16 cases), hepatocarcinoma (7) and ano-rectal carcinoma (3), AIDS for 22 (15%), mainly due to Non Hodgkin Lymphoma (10 cases) and uterine cancer (3), cardiovascular diseases for 22 (15%), post hepatitis C hepatic failure for 16 (11%), suicide for 16 (11%), and bacterial infections for 14(9%). When comparing characteristics of death in the 149 responders versus the 715 other patients, the responders were significantly more frequently: co-infected by HCV+ (45 vs. 33%), injected drug addicts (40 vs. 27%),alcoholics (38 vs. 28 %), and dyslipidemics (19 vs. 11%). In 2000,around 20% of registered deaths of HIV patients in France had occurred among good immunovirological responders. CONCLUSION: To further reduce mortality among such efficiently treated patients, attention must be focused on treatable conditions such as hepatitis C, dyslipidemia and on the prevention of malignancies such as lung cancer and cervical or ano-rectal carcinoma.