***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: Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies .  Recombinant growth hormone ( rGH ) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells , so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals . To test this concept , we administered rGH to a clinical ly defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines ( hepatitis A , hepatitis B or tetanus toxoid ) . Of the original 278 HIV-1-infected patients entering the trial , only 20 conformed to these immunological criteria and were r and omized into three groups : Group A ( n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B ( n = 5 ) and C ( n = 7 ) who received either rGH or vaccination alone , respectively . Of the eight subjects in Group A , five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies . In the controls , three of the five in group B recovered cellular responses with two producing antibodies , whereas three of the seven in Group C recovered CD4 responses , with only two producing antibodies . Significantly , whereas seven of ten patients receiving rGH treatment in Group A ( six patients ) and B ( one patient ) recovered T-cell responses to HIVp24 , only two of six in Group C responded similarly . In conclusion , reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses OBJECTIVES To characterize viro-immunological outcomes following long-term combined antiretroviral therapy ( cART ) initiated during primary HIV infection ( PHI ) or chronic HIV infection ( CHI ) and to identify factors predictive of optimal viro-immunological responder ( OVIR ) status . METHODS This was a prospect i ve , single-centre cohort study of HIV-1-infected patients on effective cART .  Total  cell-associated HIV DNA levels and T cell counts  before and during treatment were used to identify factors predictive of OVIR status { i.e. low HIV DNA level [ < 2.3 log10 copies/10(6 ) peripheral blood mononuclear cells ( P BMC s ) ] , together with normalization of the absolute/relative CD4 + T cell counts and CD4+/CD8 + ratio}. RESULTS A total of 307 patients were enrolled , of whom 35 started cART during PHI ( < 4 months post-infection ) and 272 during CHI .  HIV DNA decay was modelled with a non-linear mixed-effects model that showed two phases of HIV DNA decay , both of which were significantly more pronounced in the PHI group . At the end of follow-up , after a median of 4 years of viral suppression ( < 50 copies/mL ) , HIV DNA levels were lower in the PHI group than in the CHI group ( median = 2.15 versus 2.84 log10 copies/10(6 ) P BMC s ; P < 0.0001 ) . Immune reconstitution was more rapid and sustained in the PHI group ( median = 883 versus 619 CD4 + cells/mm(3 ) ; 41 % versus 31 % CD4 + ; CD4+/CD8 + 1.31 versus 0.77 ; all P < 0.0001 ) . Finally , OVIR status was obtained in 19/35 ( 54 % ) and 7/272 ( 3 % ) patients in the PHI and CHI groups ( P < 0.0001 ) , respectively . In a logistic regression analysis , cART initiation during PHI ( OR = 16 , 95 % CI = 3.5 - 72.3 ) and HIV DNA level < 3.3 log10 before treatment ( OR = 4.8 , 95 % CI = 1.2 - 19.3 ) were independently predictive of OVIR status . CONCLUSIONS Initiating cART during PHI represents a major opportunity to reduce HIV reservoirs and achieve optimal immune reconstitution Background : Poor CD4 lymphocyte recovery on antiretroviral therapy ( ART ) is associated with reduced function of the thymus . Palifermin ( keratinocyte growth factor ) , by providing support to the thymic epithelium , promotes lymphopoiesis in animal models of bone marrow transplantation and graft-versus-host disease . Methods : In AIDS Clinical Trials Group A5212 , a r and omized , double-blind , placebo-controlled study , 99 HIV-infected patients on ART with plasma HIV-1 RNA levels ⩽200 copies per milliliter for ≥6 months and CD4 lymphocyte counts < 200 cells per cubic milliliter were r and omized 1:1:1:1 to receive once daily intravenous administration of placebo or 20 , 40 , or 60 & mgr;g/kg of palifermin on 3 consecutive days . Results : The median change in the CD4 + T-cell count from baseline to week 12 was not significantly different between the placebo arm [ 15 ( −16 , 23 ) cells/mm3 ] and the 20-&mgr;g/kg dose [ 11 ( 2 , 32 ) cells/mm3 ] , the 40-&mgr;g/kg dose [ 12 ( −2 , 25 ) cells/mm3 ] , or the 60-&mgr;g/kg dose arm [ 8 ( −13 , 35 ) cells/mm3 ] of palifermin . No significant changes were observed in thymus size or in the number of naive T cells or recent thymic emigrants . Conclusions : Palifermin in the doses studied was not effective in improving thymic function and did not raise CD4 lymphocyte counts in HIV-infected patients with low CD4 cell counts despite virologically effective ART BACKGROUND Human immunodeficiency virus ( HIV ) is associated with increased systemic inflammation and immune activation that persist despite suppressive antiretroviral therapy ( ART ) . Herpes simplex virus type 2 ( HSV-2 ) is a common coinfection that may contribute to this inflammation . METHODS Sixty HIV type 1 (HIV-1)/HSV-2-coinfected adults on suppressive ART were r and omized 1:1:1 to 12 weeks of placebo , low-dose valacyclovir ( 500 mg twice daily ) , or high-dose valacyclovir ( 1 g twice daily ) in this 18-week trial . Co- primary outcome measures were the percentage of activated ( CD38(+)HLA-DR(+ ) ) CD8 T cells in blood , and highly sensitive C-reactive protein , interleukin 6 , and soluble intercellular adhesion molecule 1 in plasma . Secondary outcomes included additional immune , inflammatory cytokine , and endothelial activation markers . The impact of valacyclovir ( both groups combined ) on each outcome was estimated using treatment × time interaction terms in generalized estimating equation regression models . RESULTS Participants were mostly white ( 75 % ) men who have sex with men ( 80 % ) . Median age was 51 ( interquartile range [ IQR ] , 47 - 56 ) years , median duration of HIV infection was 15 ( IQR , 8 - 21 ) years , median CD4 count at enrollment was 520 ( IQR , 392 - 719 ) cells/µL , and median nadir CD4 count was 142 ( IQR , 42 - 240 ) cells/µL.  Valacyclovir was not associated with significant changes in any primary or secondary immunological outcomes in bivariate or multivariable models . Medication adherence was 97 % by self-report , 96 % by pill count , and 84 % by urine monitoring . Eight patients had adverse events deemed possibly related to the study drug ( 5 placebo , 1 low-dose , 2 high-dose ) , and 6 patients reported at least 1 HSV outbreak ( 3 placebo , 3 low-dose , 0 high-dose ) . CONCLUSIONS Valacyclovir did not decrease systemic immune activation or inflammatory biomarkers in HIV-1/HSV-2-coinfected adults on suppressive ART . CLINICAL TRIALS REGISTRATION NCT01176409 Objectives : To assess whether T-cell activation independently predicts the extent of CD4 + T-cell recovery and mortality in HIV-infected Ug and ans initiating antiretroviral therapy ( ART ) . Design : Prospect i ve cohort study . Methods : HIV-infected adults starting ART and achieving a plasma HIV RNA level ( VL ) less than 400 copies/ml by month 6 were sample d from the Ug and a AIDS Rural Treatment Outcomes ( UARTO ) cohort in Mbarara , Ug and a.  CD4 count , VL , and the percentage-activated ( CD38+HLA-DR+ ) T cells  were measured every 3 months . Results : Of 451 HIV-infected Ug and ans starting ART , most were women ( 70 % ) with median pre-ART values : age , 34 years ; CD4 count , 135 cells/&mgr;l ; and VL , 5.1 log10 copies/ml . Of these , 93 % achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months , with 8 % lost to follow-up at 3 years . Higher pre-ART CD8 + T-cell activation was associated with diminished CD4 recovery after year 1 , after adjustment for pre-ART CD4 count , VL , and sex ( P = 0.017 ) . Thirty-four participants died , 15 after month 6 . Each 10 % point increase in activated CD8 + T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count ( P = 0.048 ) . Conclusions : Higher pre-ART CD8 + T-cell activation independently predicts slower CD4 + T-cell recovery and higher persistent CD8 + T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ug and ans . Novel therapeutic strategies aim ed at preventing or reversing immune activation during ART are needed in this setting BACKGROUND In sub-Saharan Africa , the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high . We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy ( ART ) , 6-month isoniazid preventive therapy ( IPT ) , or both among HIV-infected adults with high CD4 + cell counts in Ivory Coast . METHODS We included participants who had HIV type 1 infection and a CD4 + count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization ( WHO ) guidelines . Participants were r and omly assigned to one of four treatment groups : deferred ART ( ART initiation according to WHO criteria ) , deferred ART plus IPT , early ART ( immediate ART initiation ) , or early ART plus IPT . The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome ( AIDS ) , non-AIDS-defining cancer , non-AIDS-defining invasive bacterial disease , or death from any cause at 30 months . We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies . RESULTS A total of 2056 patients ( 41 % with a baseline CD4 + count of ≥500 cells per cubic millimeter ) were followed for 4757 patient-years . A total of 204 primary end-point events were observed ( 3.8 events per 100 person-years ; 95 % confidence interval [ CI ] , 3.3 to 4.4 ) , including 68 in patients with a baseline CD4 + count of at least 500 cells per cubic millimeter ( 3.2 events per 100 person-years ; 95 % CI , 2.4 to 4.0 ) . Tuberculosis and invasive bacterial diseases accounted for 42 % and 27 % of primary end-point events , respectively . The risk of death or severe HIV-related illness was lower with early ART than with deferred ART ( adjusted hazard ratio , 0.56 ; 95 % CI , 0.41 to 0.76 ; adjusted hazard ratio among patients with a baseline CD4 + count of ≥500 cells per cubic millimeter , 0.56 ; 95 % CI , 0.33 to 0.94 ) and lower with IPT than with no IPT ( adjusted hazard ratio , 0.65 ; 95 % CI , 0.48 to 0.88 ; adjusted hazard ratio among patients with a baseline CD4 + count of ≥500 cells per cubic millimeter , 0.61 ; 95 % CI , 0.36 to 1.01 ) . The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies . CONCLUSIONS In 
    Output:
    
DIR is associated with a marked increase in mortality in most studies but definitions vary widely .