To date, the most effective treatment of HIV-1 is a combination antiretroviral therapy (cART), which reduces viral replication and reverses pathology. We investigated the effect of cART (RT and protease inhibitors) on the content of extracellular vesicles (EVs) released from HIV-1-infected cells. We have previously shown that EVs contain non-coding HIV-1 RNA, which can elicit responses in recipient cells. In this manuscript, we show that TAR RNA levels demonstrate little change with the addition of cART treatment in cell lines, primary macrophages, and patient biofluids. We determined possible mechanisms involved in the selective packaging of HIV-1 RNA into EVs, specifically an increase in EV-associated hnRNP A2/B1. More recent experiments have shown that several other FDA-approved drugs have the ability to alter the content of exosomes released from HIV-1-infected cells. These findings on cART-altered EV content can also be applied to general viral inhibitors (interferons) which are used to treat other chronic infections. Additionally, we describe unique mechanisms of ESCRT pathway manipulation by antivirals, specifically the targeting of VPS4. Collectively, these data imply that, despite antiretroviral therapy, EVs containing viral products are continually released and may cause neurocognitive and immunological dysfunction.

The potential role of gender in the occurrence of HIV-related neurocognitive impairment (NCI) and associations with markers of HIV-related immune activity has not been previously examined. In this study 149 antiretroviral-naïve seropositive subjects in Nigeria (SP, 92 women and 57 men) and 58 seronegative (SN, 38 women and 20 men) were administered neuropsychological testing that assessed 7 ability domains. From the neuropsychological test scores was calculated a global deficit score (GDS), a measure of overall NCI. Percentages of circulating monocytes and plasma HIV RNA, soluble CD163 and soluble CD14 levels were also assessed. HIV SP women were found to be younger, more educated and had higher CD4+ T cell counts and borderline higher viral load measures than SP men. On the neuropsychological testing, SP women were more impaired in speed of information processing and verbal fluency and had a higher mean GDS than SN women. Compared to SP men, SP women were also more impaired in speed of information processing and verbal fluency as well as on tests of learning and memory. Numbers of circulating monocytes and plasma sCD14 and sCD163 levels were significantly higher for all SP versus all SN individuals and were also higher for SP women and for SP men versus their SN counterparts. Among SP women, soluble CD14 levels were slightly higher than for SP men, and SP women had higher viral load measurements and were more likely to have detectable virus than SP men. Higher sCD14 levels among SP women correlated with more severe global impairment, and higher viral load measurements correlated with higher monocyte numbers and sCD14 and sCD14 levels, associations that were not observed for SP men. These studies suggest that the risk of developing NCI differ for HIV infected women and men in Nigeria and, for women, may be linked to effects from higher plasma levels of HIV driving activation of circulating monocytes.

Background:Stroke is the second leading cause of death and the leading cause of adult disability worldwide. A better understanding of stroke risk factors and outcome may help guide efforts at reducing the community burden of stroke. This study aimed to understand stroke risk factors, imaging subtypes, and 30-day outcomes among adult Nigerians.Materials and Methods:We prospectively recruited all patients presenting with acute stroke at the National Hospital Abuja between January 2010 and June 2012. We assessed clinical and laboratory variables, as well as brain computerized tomography, magnetic resonance imaging, and carotid Doppler ultrasound scans. We also assessed case fatality and functional outcome at 30 days after stroke.Results:Of 272 patients studied, 168 (61.8%) were males. Age at presentation (mean ± standard deviation) was 56.4 ± 12.7 years in males and 52.9 ± 14.8 years in females (P = 0.039). Neuroimaging was obtained in 96.7% patients, revealing cerebral infarction (61.8%), intracerebral hemorrhage (ICH) (34.8%), and subarachnoid hemorrhage (SAH) (3.4%). Carotid plaques or stenosis ≥50% were detected in 53.2% patients with cerebral infarction. Stroke risk factors included hypertension (82.7%), obesity (32.6%), diabetes (23.5%), hyperlipidemia (18.4%), atrial fibrillation (9.2%), and cigarette smoking (7.7%). At 30 days after stroke, case-fatality rate was 18.8%, whereas modified Rankin Scale (mRS) scores for cerebral infarction, ICH, and SAH were 3.71, 4.21, and 4.56, respectively. Atrial fibrillation, a previous stroke, and age older than 50 years were all associated with worse mRS scores at 30 days.Conclusion:Although hypertension, obesity, diabetes mellitus, and atrial fibrillation were important stroke risk factors, in many patients, these were detected only after a stroke. While the commonest stroke subtype was cerebral infarction, observed in almost two-third of patients, SAH was associated with the highest case-fatality rate at 30 days of 44.4%. Larger population-based studies may provide additional data on stroke incidence and outcome among Nigerians.

The case records of 53 consecutive Nigerian inpatients with stroke in the University of Maiduguri Teaching Hospital, Maiduguri were retrospectively reviewed. The mean age at presentation was 55 years and the male to female ratio was 2.5:1. The mean duration of symptoms before presentation was 11.1 weeks and the average duration of stay in hospital was 3 weeks. Thirty-three (63%) of the lesions were infarctive and 19 (37%) were haemorrhagic. Only 3 (6%) patients gave a history of prior transient ischaemic attacks (TIAs). Forty-two (79%) patients were hypertensive at presentation out of which 27 (64%) had the hypertension diagnosed for the first time. Four (8%) patients were non-insulin dependent diabetics. There were 11 hospital deaths (21%). Thus hypertension, more than half undiagnosed at admission, was the most common risk factor for stroke in the hospital population studied.

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