Plasma CXCL10 correlates with HAND in HIV-infected women.

HIV-associated neurocognitive disorder (HAND) is characterized by chronic immune activation. We aimed to identify biomarkers associated with HAND and to investigate their association with cognitive function and sex, in a homogenous cohort of HIV-infected (HIV+) young adults, parenterally infected during early childhood. One hundred forty-four HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1ß, IL-6, CCL2, CXCL8, CXCL10, and TNF-α were measured in plasma in all participants and in cerebrospinal fluid (CSF) in a subgroup of 56 study participants. Biomarkers were compared with neurocognitive outcomes, and the influence of sex and HIV disease biomarkers was assessed. In this cohort of young adults (median age of 24 years), the rate of neurocognitive impairment (NCI) was 36.1%. Median current CD4+ count was 479 cells/mm3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma, controlling for sex, higher levels of IL-6 and TNF-α were associated with NCI (p < 0.05). Plasma CXCL10 showed a significant interaction with sex (p = 0.02); higher values were associated with NCI in women only (p = 0.02). Individuals with undetectable viral load had significantly lower plasma CXCL10 (p < 0.001) and CCL2 (p = 0.02) levels, and CSF CXCL10 (p = 0.01), IL-6 (p = 0.04), and TNF-α (p = 0.04) levels. NCI in young men and women living with HIV was associated with higher IL-6 and TNF-α in plasma, but not in the CSF. CXCL10 was identified as a biomarker of NCI specifically in women with chronic HIV infection.

Latent toxoplasmosis is associated with neurocognitive impairment in young adults with and without chronic HIV infection.

We evaluated the impact of latent toxoplasmosis (LT) on neurocognitive (NC) and neurobehavioural functioning in young adults with and without chronic HIV infection, using a standardised NC test battery, self-reported Beck Depression Inventory, Frontal System Behavior Scale, MINI-International Neuropsychiatric Interview and risk-assessment battery. 194 young adults (median age 24years, 48.2% males) with chronic HIV infection (HIV+) since childhood and 51 HIV seronegative (HIV-) participants were included. HIV+ individuals had good current immunological status (median CD4: 479 cells/µl) despite a low CD4 nadir (median: 93 cells/µl). LT (positive anti-Toxoplasma IgG antibodies) was present in one third of participants. The impairment rates in the HIV- with and without Toxo were not significantly different (p=0.17). However, we observed an increasing trend (p<0.001) in impairment rates with HIV and LT status: HIV-/LT- (6.1%); HIV-/LT+ (22%), HIV+/LT- (31%), HIV+/LT+ (49%). In a multivariable analysis using the entire study group there were main effects on cognition for HIV and also for LT. Within the HIV+ group LT was associated with worse performance globally (p=0.006), in memory (p=0.009), speed of information processing (p=0.01), verbal (p=0.02) and learning (p=0.02) domains. LT was not associated with depressive symptoms, frontal systems dysfunction or risk behaviors in any of the groups. HIV participants with lower Toxoplasma antibody concentration had worse NC performance, with higher GDS values (p=0.03) and worse learning (p=0.002), memory (p=0.006), speed of information processing (p=0.01) T scores. Latent Toxoplasmosis may contribute to NC impairment in young adults, including those with and without chronic HIV infection.

Major HIV resistance mutations in untreated Romanian patients.

Drug resistance mutations are frequently detected in antiretroviral-naive HIV positive patients, however the data on transmitted resistance in non-B subtypes are limited. As HIV1 subtype F is prevalent in Romania, our goal is to analyze resistance mutations in the pol gene of HIV-1 isolates from drug-naive Romanian patients. HIV-1 pol gene from 12 untreated patients, newly diagnosed (n = 6) and chronically infected (n=6), with detectable HIV RNA viral load was genotyped and the viral subtype was determined by using the Stanford database algorithm. 8/12 strains belonged to the F subtype, 1/12 to the G subtype, and the rest of the studied strains appeared to be K/F, A/F and J/F inter-subtype recombinant forms. The prevalence of HIV-1 strains with at least one major drug resistance mutation in the studied group was unexpectedly high. Major mutations associated with NRTI, NNRTI and PI resistance were detected in 6/12 patients, 2/12 patients and 3/12 patients, respectively; in addition all viral strains had minor mutations in the protease gene. Newly diagnosed patients harbored resistant variants more often than chronically infected ones (4/6 vs. 2/6) did. These data support the use of genotypic resistance testing in treatment-naive HIV positive patients, in order to guide the selection of the first line of antiretrovirals, due to the fact that persons with transmitted drug resistance have a higher risk for both virologic failure and development of resistance at treatment initiation.