***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 : The contribution of immune activation to accelerated HIV-disease progression in older individuals has not been delineated . Methods : Prospect i ve multicenter cohort of older ( ≥45 years ) and younger ( 18–30 years ) HIV-infected adults initiating 192 weeks of antiretroviral therapy ( ART ) .  Longitudinal models of CD4 cell restoration examined associations with age-group , thymic volume , immune activation , and viral load . Results : Forty-five older and 45 younger adults ( median age 50 and 26 years , respectively ) were studied . Older patients had fewer naive CD4 cells ( P < 0.001 ) and higher HLA-DR/CD38 expression on CD4 ( P = 0.05 ) and CD8 cells ( P = 0.07 ) than younger patients at any time on ART . The rate of naive and total CD4 cell increase was similar between age groups , but older patients had a faster mean rate of B-cell increase ( by + 0.7 cells/week ; P = 0.01 ) , to higher counts than healthy controls after 192 weeks ( P = 0.003 ) . Naive CD4 increases from baseline were associated with immune activation reductions ( as declines from baseline of % CD8 cells expressing HLA-DR/CD38 ; P < 0.0001 ) , but these increases were attenuated in older patients , or in those with small thymuses . A 15 % reduction in activation was associated with naive gains of 29.9 and 6.2 cells/&mgr;l in younger , versus older patients , or with gains of 25.7 , 23.4 , and 2.1 cells/&mgr;l in patients with the largest , intermediate , and smallest thymuses , respectively ( P < 0.01 for interactions between activation reduction and age-group or thymic volume ) . Conclusion : Older patients had significant B-cell expansion , higher levels of immune activation markers , and significantly attenuated naive CD4 cell gains associated with activation reduction Objective : To prospect ively examine differences in baseline characteristics and study outcomes between HIV‐infected women and men during a clinical trial of  nucleoside analogue therapy .  Methods : ACTG 175 r and omized HIV‐infected patients with CD4 + counts between 200 and 500 cells/mm3 to one of four nucleoside analogue regimens : zidovudine ( ZDV ) , didanosine ( ddl ) , ZDV + ddI , or ZDV + zalcitabine ( ddC ) . Differences in time to first dose modification , voluntary withdrawal , development of toxicity and symptomatology , and AIDS progression were compared by gender . Results : The study included 438 women and 2029 men . Baseline values of HIV RNA plasma concentrations were significantly lower for women ( 0.3 log10 ) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4 + count . Women reported reducing dosage and discontinue ddI‐containing regimens more frequently than men did ; adjustment for weight did not completely explain this difference . Women were at lower risk than men for progression to a study endpoint ( 19 % of women versus 24 % of men ; p < .0001 ) . Among those antiretroviral‐naive study subjects receiving ZDV , men were four times more likely to progress to a study endpoint than women . Conclusions : Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial . The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral‐naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication , CD4 + decline , and responses to nucleoside analogue therapy Objective : To determine the impact of age and initial HAART regimen class on virologic and immunologic response within 24 months after initiation . Design : Pooled analysis of data from 19 prospect i ve cohort studies in the North American AIDS Cohort Collaboration on Research and Design ( NA-ACCORD ) . Methods : Twelve thous and , one hundred and ninety-six antiretroviral-naive adults who initiated HAART between 1998 and 2008 using a boosted protease inhibitor-based regimen or a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen were included in our study . Discrete time-to-event models estimated adjusted hazard odds ratios ( aHOR ) and 95 % confidence intervals ( CIs ) for suppressed viral load ( ≤500 copies/ml ) and , separately , at least 100 cells/μl increase in CD4 cell count . Truncated , stabilized inverse probability weights accounted for selection biases from discontinuation of initial regimen class . Results : Among 12 196 eligible participants ( mean age = 42 years ) , 50 % changed regimen classes after initiation ( 57 and 48 % of whom initiated protease inhibitor and NNRTI-based regimens , respectively ) . Mean CD4 cell count at initiation was similar by age . Virologic response to treatment was less likely in those initiating using a boosted protease inhibitor [ aHOR = 0.77 ( 0.73 , 0.82 ) ] , regardless of age . Immunologic response decreased with increasing age [ 18–<30 : ref ; 30–<40 : aHOR = 0.92 ( 0.85 , 1.00 ) ; 40–<50 : aHOR = 0.85 ( 0.78 , 0.92 ) ; 50–<60 : aHOR = 0.82 ( 0.74 , 0.90 ) ; ≥60 : aHOR = 0.74 ( 0.65 , 0.85 ) ] , regardless of initial regimen . Conclusion : We found no evidence of an interaction between age and initial antiretroviral regimen on virologic or immunologic response to HAART ; however , decreased immunologic response with increasing age may have implication s for age-specific when-to-start guidelines BACKGROUND Individuals infected with human immunodeficiency virus ( HIV ) have higher risk than HIV-negative individuals for diseases associated with aging . T-cell senescence , characterized by expansion of cells lacking the costimulatory molecule CD28 , has been hypothesized to mediate these risks . METHODS We measured the percentage of CD28(-)CD4(+ ) and CD8(+ ) T cells  from  HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group ( ACTG ) antiretroviral therapy ( ART ) studies and the ALLRT ( ACTG Longitudinal Linked R and omized Trials ) cohort , and from 48 HIV-negative adults . Pretreatment and 96-week posttreatment % CD28(- ) cells were assessed using linear regression for associations with age , sex , race/ethnicity , CD4 count , HIV RNA , ART regimen , and hepatitis C virus ( HCV ) infection . RESULTS In total , 1291 chronically HIV-infected adults were studied . Pretreatment , lower CD4 count was associated with higher % CD28(-)CD4(+ ) and % CD28(-)CD8(+ ) cells . For CD8(+ ) cells , younger age and HCV infection were associated with a lower % CD28(- ) . ART reduced % CD28(- ) levels at week 96 among virally suppressed individuals . Older age was strongly predictive of higher % CD28(-)CD8(+ ) . Compared to HIV-uninfected individuals , HIV-infected individuals maintained significantly higher % CD28(- ) . CONCLUSIONS Effective ART reduced the proportion of CD28(- ) T cells . However , levels remained abnormally high and closer to levels in older HIV-uninfected individuals . This finding may inform future research of increased rates of age-associated disease in HIV-infected adults Background Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals . The factors associated with D-dimer levels during HIV infection , however , remain poorly understood . Methods In this cross-sectional study , participants in three r and omized controlled trials with measured D-dimer levels were included ( N = 9,848 ) . Factors associated with D-dimer were identified by linear regression . Covariates investigated were : age , gender , race , body mass index , nadir and baseline CD4 + count , plasma HIV RNA levels , markers of inflammation ( C-reactive protein [ CRP ] , interleukin-6 [ IL-6 ] ) , antiretroviral therapy ( ART ) use , ART regimens , co-morbidities ( hepatitis B/C , diabetes mellitus , prior cardiovascular disease ) , smoking , renal function ( estimated glomerular filtration rate [ eGFR ] and cystatin C ) and cholesterol . Results Women from all age groups had higher D-dimer levels than men , though a steeper increase of D-dimer with age occurred in men . Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels . In this subgroup , the degree of hepatic fibrosis , as demonstrated by higher hyaluronic acid levels , but not viral load of hepatitis viruses , was positively correlated with D-dimer . Other factors independently associated with higher D-dimer levels were black race , higher plasma HIV RNA levels , being off ART at baseline , and increased levels of CRP , IL-6 and cystatin C. In contrast , higher baseline CD4 + counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels . Conclusions D-dimer levels increase with age in HIV+ men , but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases . In hepatitis B/C co-infected individuals , hepatic fibrosis , but not hepatitis viral load , was associated with higher D-dimer levels There is intense interest in developing curative interventions for HIV . How such a cure will be quantified and defined is not known . We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor . Sample s from blood , spinal fluid , lymph node , and gut were analyzed in multiple laboratories using different approaches . No HIV DNA or RNA was detected in peripheral blood mononuclear cells ( P BMC ) , spinal fluid , lymph node , or terminal ileum , and no replication-competent virus could be cultured from P BMC s. However , HIV RNA was detected in plasma ( 2 laboratories ) and HIV DNA was detected in the rectum ( 1 laboratory ) at levels considerably lower than those expected in ART-suppressed patients . It was not possible to obtain sequence data from plasma or gut , while an X4 sequence from P BMC did not match the pre-transplant sequence . HIV antibody levels were readily detectable but declined over time ; T cell responses were largely absent . The occasional , low-level PCR signals raise the possibility that some HIV nucleic acid might persist , although they could also be false positives . Since HIV levels in well-treated individuals are near the limits of detection of current assays , more sensitive assays need to be developed and vali date d. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure BACKGROUND Short-course antiretroviral therapy ( ART ) in primary human immunodeficiency virus ( HIV ) infection may delay disease progression but has not been adequately evaluated . METHODS We r and omly assigned adults with primary HIV infection to ART for 48 weeks  , ART for 12 weeks , or no ART ( st and ard of care ) , with treatment initiated within 6 months after seroconversion . The primary end point was a CD4 + count of less than 350 cells per cubic millimeter or long-term ART initiation . RESULTS A total of 366 participants ( 60 % men ) underwent r and omization to 48-week ART ( 123 participants ) , 12-week ART ( 120 ) , or st and ard care ( 123 ) , with an average follow-up of 4.2 years . The primary end point was reached in 50 % of the 48-week ART group , as compared with 61 % in each of the 12-week ART and st and ard-care groups . The average hazard ratio was 0.63 ( 95 % confidence interval [ CI ] , 0.45 to 0.90 ; P=0.01 ) for 48-week ART as compared with st and ard care and was 0.93 ( 95 % CI , 0.67 to 1.29 ; P=0.67 ) for 12-week ART as compared with st and ard care . The proportion of participants who had a CD4 + count of less than 350 cells per cubic millimeter was 28 % in the 48-week ART group , 40 % in the 12-week group , and 40 % in the st and ard-care group . Corresponding values for long-term ART initiation were 22 % , 21 % , and 22 % . The median time to the primary end point was 65 weeks ( 95 % CI , 17 to 114 ) longer with 48-week ART than with st and ard care . Post hoc analysis identified a trend toward 
    Output:
    
Participation of demographic subgroups differed by intervention type and study location .
Rates of participation of demographic groups of interest did not vary with time .
Limited data suggest efficacy , particularly of early therapy initiation followed by treatment interruption , may vary by demographic variables , in this case sex .