The Romanian cohort can provide valuable information about the effect of chronic HIV-infection and exposure to combined antiretroviral therapy (cART) on the developing brain, based on its unique characteristics: young adults infected parenterally with HIV clade F in the late 1980s and exposed to cART for a decade. We conducted a prospective study using a neuropsychological test battery validated in other international HIV cohorts, in order to evaluate the rate and severity of neurocognitive impairment in a group of young Romanian adults. The 49 HIV-infected (HIV+) participants and the 20 HIV negative (HIV−) controls were similar for age and gender, although the HIV− group tended to be more educated. We found higher cognitive impairment prevalence in the HIV+ group (59.1 %) versus the HIV− group (10 %), and the impairment rate remained significantly higher even when the groups were matched based on the educational level (38.7 % for the HIV+ group vs. 10.0 % for the HIV− controls; p=0.025). The nadir CD4 count was <200 in 71.4 % of patients, but at the time of neurocognitive assessment, 89.5 % of patients had normal immunological status and 81.8 % undetectable HIV load. Among the HIV-impaired group, 26 % of the participants had syndromic impairment while the other 74 % had asymptomatic neurocognitive impairment. We found a high prevalence of neurocognitive dysfunction in the Romanian young adults growing-up with HIV. The greatest HIV-related cognitive deficits were in the domains of executive and motor functioning, consistent with a frontosubcortical pattern.

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Despite less advanced disease in women, long-term HIV infection has an equally detrimental effect on cognitive performances of both sexes, in all cognitive domains, except the psychomotor domain where women are preferentially affected.

Objectives: 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.Methods: 144 HIV+ Romanian participants (51% women) without major confounders underwent standardized neurocognitive and medical evaluation in a cross-sectional study. IFN-γ, IL-1β, 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 to neurocognitive outcomes, and the influence of sex and HIV disease biomarkers were assessed. Results: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/mm 3 and 36.8% had detectable plasma viral load. Women had better HIV-associated overall status. In plasma,

To prevent acquisition of HIV through oral sex, drugs used for preexposure prophylaxis (Prep) need to diffuse in saliva. We measured tenofovir (TFV) and emtricitabine (FTC) concentrations simultaneously in the plasma and saliva of 41 HIV-infected patients under stable antiretroviral treatment. Mean ratios of saliva/ plasma concentration were 3% (؎4%) and 86.9% (؎124%) for TFV and FTC, respectively. Tenofovir disoproxil fumarate (TDF) should be used in combination with FTC to prevent oral acquisition of HIV.Thirty years into the HIV pandemic, a high incidence of new HIV infections persists, particularly in the subgroup of men having sex with men (MSM), where HIV transmission is sustained (16). Innovative approaches to prevent HIV transmission include the use of antiretrovirals as preventive tools, known as preexposure prophylaxis (Prep), either as oral pills or topical microbicides containing an active antiviral agent (13). Recent studies have shown a partial reduction in HIV acquisition in women using a vaginal tenofovir gel (1) and in MSM taking a daily oral tenofovir disoproxil fumarate (TDF)-emtricitabine (FTC) combination pill (11), the favored combination for Prep.While it is agreed that oral sex carries a much lower HIV infection risk than vaginal and anal sex, studies have convincingly demonstrated that both insertive and receptive oral sex are independent risk factors for transmission of HIV (6,19,20). The risk increases with frequency of activity, the presence of oral ulcers, oropharyngeal inflammation, or sexually transmitted infections in the oropharynx. This route of transmission should not be underestimated, in particular in MSM, where oral sex is rarely protected (8). In order for Prep to prevent HIV transmission through oral sex also, antiviral drugs should be taken orally, and their saliva concentrations should be sufficient to inhibit viral replication. Yet, no data are available on the penetration of tenofovir (TFV) and FTC in saliva. The aim of this work is to measure TFV and FTC saliva concentrations and saliva-to-plasma ratios in HIV-infected patients receiving either a TDF-or a TDF-FTC-based treatment.HIV-infected patients regularly followed in our HIV clinic were included if they were receiving a stable antiretroviral regimen, including 245 mg TDF daily and/or 200 mg FTC daily for at least 3 months, and gave informed consent. The study was approved by the Paris Saint-Louis Institutional Review Board. Blood and saliva samples were collected simultaneously during a routine follow-up evaluation of their HIV infection. Saliva samples were obtained by having participants spit 10 ml saliva in a sterile pot. To confirm that saliva had been sampled, samples were tested by validated colorimetric assays for total proteins (Biuret test) and saliva ␣-amylase (S type, enzymatic method) levels, using a Roche Modular analyzer (Roche Diagnostics France, Meylan, France). Both plasma and saliva TFV and FTC levels were measured by a validated high-performance liquid chromatography with tandem mass spectromet...