***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND It is well established that there is mutual interaction between the neuroendocrines and immune systems and that the disturbance in any one system could affect the function of the other . While there is a large body of evidence suggesting negative impact of human immunodeficiency virus type 1B ( HIV-1B ) infection on both immune and neuroendocrine systems , the consequence of HIV-1 clade C infection ( with structural differences from HIV-1B virus ) on these systems is not clearly understood . METHODS We carried out a 2-year longitudinal study on plasma profile of adrenocorticosteroids , including cortisol and DHEAS and their relationship with declining CD4 + cell counts in neurologically asymptomatic HIV-C infected individuals ( N=84 ) in order to underst and the impact of HIV-1 clade C infection on adrenocortical dysfunction and its relationship with the progressive decline in the cell mediated immunity . RESULTS We found that while plasma cortisol levels increased significantly at baseline in HIV-1C infected individuals compared to those in HIV-negative controls ( HIV-1C+ , 9.83+/-0.39 vs controls , 8.04+/-0.45 ; p<0.01 ) , there was a significant decrease in DHEAS in HIV-1C+ individuals , compared to that in HIV-negative controls ( 81.02+/-4.9 vs 185.1+/-12.03 , p<0.001 ) , and consequently a significant increase in cortisol : DHEAS ratio in HIV-1 clade C infected persons ( 0.19+/-0.002 vs control 0.058+/-0.006 ; p<0.001 ) . Moreover , in HIV-1C infected individuals , there was a strong positive correlation between DHEAS and CD4 cells ( r=0.2 ; p<0.05 ) , and a strong negative correlation between cortisol , as well as cortisol : DHEAS ratio and CD4 cells ( r=-0.25 ; p<0.01 ; and r=-0.31 ; p<0.001 , respectively ) . CONCLUSIONS These findings suggest the persistent and progressive adrenocortical dysfunction during the asymptomatic phase of HIV infection , and that the evaluation of increase in plasma cortisol , a decrease in DHEAS , and an increase in cortisol : DHEAS ratio may serve as important biomarkers preceding the impending down regulation of CD4 cell counts and progressive decline in the immune system function in HIV-1C infection . Furthermore , these findings may indicate the dysregulation of 3beta-hydroxysteroid dehydrogenase ( 3beta-HSD ) activity , the enzyme involved in the bio synthesis of cortisol and DHEA through the pregnenolone-progesterone pathway , and that it may offer an opportunity for drug discovery targeting re-regulation of 3beta-HSD activity for potential therapeutic application in HIV-1C infection Background : Women progress to death at the same rate as men despite lower plasma HIV RNA ( viral load ) . We investigated sex-specific differences in immune activation and inflammation as a potential explanation . Methods : Inflammatory and immune activation markers [ interferon & ggr ; , tumor necrosis factor ( TNF ) & agr ; , IL-6 , IL-18 , IFN-&ggr ;– induced protein 10 , C-reactive protein ( CRP ) , lipopolysaccharide , and sCD14 ] were measured at weeks 0 , 24 , and 48 after combination antiretroviral therapy ( cART ) in a r and om subcohort ( n = 215 ) who achieved virologic suppression in ACTG A5175 ( Prospect i ve Evaluation of Antiretrovirals in Re source -Limited Setting s ) . Association between sex and changes in markers post-cART was examined using r and om effects models . Average marker differences and 95 % confidence intervals were estimated using multivariable models . Results : At baseline , women had lower median log10 viral load ( 4.93 vs 5.18 copies per milliliter , P = 0.01 ) , CRP ( 2.32 vs 4.62 mg/L , P = 0.01 ) , detectable lipopolysaccharide ( 39 % vs 55 % , P = 0.04 ) , and sCD14 ( 1.9 vs 2.3 µg/mL , P = 0.06 ) vs men . By week 48 , women had higher interferon & ggr ; ( 22.4 vs 14.9 pg/mL , P = 0.05 ) , TNF-&agr ; ( 11.5 vs 9.5 pg/mL , P = 0.02 ) , and CD4 ( 373 vs 323 cells per cubic millimeter , P = 0.02 ) . In multivariate analysis , women had greater increases in CD4 and TNF-&agr ; but less of a decrease in CRP and sCD14 compared with men . Conclusions : With cART-induced viral suppression , women have less reduction in key markers of inflammation and immune activation compared with men . Future studies should investigate the impact of these sex-specific differences on morbidity and mortality Objective : Psychological risk factors ( PRFs ) are associated with impaired learning and memory in HIV-infected ( HIV+ ) women . We determined the dynamic nature of the effects of PRFs and HIV serostatus on learning and memory over time . Design : Multicenter , prospect i ve cohort study . Methods : Every 2 years between 2009 and 2013 ( three times ) , 646 HIV+ and 300 demographically similar HIV-uninfected ( HIV− ) women from the Women 's Interagency HIV Study completed neuropsychological testing and question naires measuring PRFs [ perceived stress , posttraumatic stress disorder ( PTSD ) symptoms , depressive symptoms ] . Using mixed-effects regressions , we examined separate and interactive associations between HIV-serostatus and PRFs on performance over time . Results : HIV+ and HIV− women had similar rates of PRFs . Fluency was the only domain in which performance over time depended on the combined influence of HIV-serostatus and stress or PTSD ( P < 0.05 ) , not depression . In HIV , higher stress and PTSD were associated with a greater cognitive decline in performance ( P < 0.05 ) vs. lower stress and PTSD . Irrespective of time , performance on learning and memory depended on the combined influence of HIV-serostatus and stress or PTSD ( P ⩽ 0.05 ) . In the context of HIV , stress and PTSD were negatively associated with performance . Effects were pronounced on learning among HIV+ women without effective treatment or viral suppression . Regardless of time or HIV-serostatus , all PRFs were associated with lower speed , global neuropsychological , and executive function . Conclusion : More than depression , perceived stress and PTSD symptoms are treatment targets to potentially improve fluency , learning , and memory in women living with HIV particularly when HIV treatment is not optimal Objective : Inflammatory biomarkers associated with cardiovascular disease are elevated in HIV-infected persons . These biomarkers improve with antiretroviral therapy ( ART ) but do not normalize to values observed in HIV-uninfected adults . Little is known regarding biomarkers of inflammation in HIV-infected Peruvians , in whom an increased burden of infectious diseases may exacerbate inflammation , and women , in whom sex difference may alter inflammation compared with men . Methods : Peruvians initiating first-line ART were enrolled in a prospect i ve observational study . Individuals with suppression of HIV RNA plasma loads to less than 30 copies/ml when determined quarterly over 24 months of ART  , had biomarkers of inflammation and cellular activation measured pre-ART and at 24-months of ART , and evaluated for associations with sex and clinical parameters . Results : Pre-ART high-sensitivity C-reactive protein ( hsCRP ) values of men were in the high-risk cardiovascular disease category ( > 3.0 mg/l ) more frequently compared with women ( P = 0.02 ) ; most women 's values were in the low/average-risk categories . At 24 months of suppressive ART , hsCRP concentrations decreased in men ( P = 0.03 ) , but tended to increase in women , such that the proportion with high-risk hsCRP did not differ by sex . Pre-ART , soluble CD163 concentrations were higher in women compared with men ( P = 0.02 ) , and remained higher after 24 months of suppressive ART ( P = 0.02 ) . All other inflammatory biomarkers ( P < 0.03 ) decreased across sexes . Biomarker concentrations were not associated with BMI or coinfections . Conclusion : Elevated inflammatory biomarkers persisted despite 24 months of suppressive ART in a subset of Peruvians , and to a greater extent in women compared with men . These findings suggest that lifestyle or pharmacologic interventions may be required to optimize the health of HIV-infected Peruvians , particularly women Background Levels of high-sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , and D-dimer predict mortality in HIV patients on antiretroviral therapy ( ART ) with relatively preserved CD4 + T cell counts . We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART . Methods  Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP , IL-6 and D-dimer .  Using a nested case-control study design , the biomarkers were measured for 187 deaths and two controls matched on age , sex , clinical site , follow-up time and CD4 + cell counts . Odds ratios were estimated using conditional logistic regression . In addition , for a r and om sample of 100 patients , biomarkers were measured at baseline and 6 months following r and omization to determine whether ART altered their levels . Results Median baseline biomarkers levels for cases and controls , respectively , were 11.25 vs. 3.6 mg/L for hsCRP , 1.41 vs. 0.98 mg/L for D-dimer , and 9.02 vs. 4.20 pg/mL for IL-6 ( all p<0.0001 ) . Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 ( 95 % CI : 1.9–6.7 ) for hsCRP , 2.6 ( 95%CI 1.4–4.9 ) for D-dimer , and 3.8 ( 95 % CI : 1.8–7.8 ) for IL-6 . These associations were stronger for deaths that occurred more proximal to the biomarker measurements . Levels of D-dimer and IL-6 , but not hsCRP , were significantly lower at month 6 after commencing ART compared to baseline ( p<0.0001 ) . Conclusions Among patients with advanced HIV disease , elevated pre-ART levels of hsCRP , IL-6 and D-dimer are strongly associated with early mortality after commencing ART . Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART . Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted . Trial Registration Parent Study : Clinical Trials.gov Background In the Strategies for Management of Anti-Retroviral Therapy trial , all-cause mortality was higher for participants r and omized to intermittent , CD4-guided antiretroviral treatment ( ART ) ( drug conservation [ DC ] ) than continuous ART ( viral suppression [ VS ] ) . We hypothesized that increased HIV-RNA levels following ART interruption induced activation of tissue factor pathways , thrombosis , and fibrinolysis . Methods and Findings Stored sample s were used to measure six biomarkers : high sensitivity C-reactive protein ( hsCRP ) , interleukin-6 ( IL-6 ) , amyloid A , amyloid P , D-dimer , and prothrombin fragment 1 + 2 . Two studies were conducted : ( 1 ) a nested case – control study for study ing biomarker associations with mortality , and ( 2 ) a study to compare DC and VS participants for biomarker changes . For ( 1 ) , markers were determined at study entry and before death ( latest level ) for 85 deaths and for two controls ( n = 170 ) matched on country , age , sex , and date of r and omization .  Odds ratios ( ORs ) were estimated with logistic regression . For each biomarker , each of the three upper quartiles was compared to the lowest quartile . For ( 2 ) , the biomarkers were assessed for 249 DC and 250 VS participants at study entry and 1 mo following r and omization . Higher levels of hsCRP , IL-6 , and D-dimer at study entry were significantly associated with an increased risk of all-cause mortality . Unadjusted ORs ( highest versus lowest quartile ) were 2.0 ( 95 % confidence interval [ CI ] , 1.0–4.1 ; p = 0.05 ) , 8.3 ( 95 % CI , 3.3–20.8 ; p < 0.0001 ) , and 12.4 ( 95 % CI , 4.2–37.0 ; p < 0 
    Output:
    
A power analysis showed that few HIV studies have sufficient power to address male/female differences in NCI but studies with adequate power find evidence of greater NCI in WLWH , particularly in the domains of memory , speed of information processing , and motor function .
Sex is an important determinant of NCI in HIV , and may relate to male/female differences in cognitive reserve , comorbidities ( mental health and substance use disorders ) , and biological factors ( e.g. , inflammation , hormonal , genetic )