***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 Mortality in people in Africa with HIV infection starting antiretroviral therapy ( ART ) is high , particularly in those with advanced disease . We assessed the effect of a short period of community support to supplement clinic-based services combined with serum cryptococcal antigen screening . METHODS We did an open-label , r and omised controlled trial in six urban clinics in Dar es Salaam , Tanzania , and Lusaka , Zambia . From February , 2012 , we enrolled eligible individuals with HIV infection ( age ≥18 years , CD4 count of < 200 cells per μL , ART naive ) and r and omly assigned them to either the st and ard clinic-based care supplemented with community support or st and ard clinic-based care alone , stratified by country and clinic , in permuted block sizes of ten . Clinic plus community support consisted of screening for serum cryptococcal antigen combined with antifungal therapy for patients testing antigen positive , weekly home visits for the first 4 weeks on ART by lay workers to provide support , and in Tanzania alone , re-screening for tuberculosis at 6 - 8 weeks after ART initiation . The primary endpoint was all-cause mortality at 12 months , analysed by intention to treat . This trial is registered with the International St and ard R and omised Controlled Trial Number registry , number ISCRTN 20410413 . FINDINGS Between Feb 9 , 2012 , and Sept 30 , 2013 , 1001 patients were r and omly assigned to clinic plus community support and 998 to st and ard care . 89 ( 9 % ) of 1001 participants in the clinic plus community support group did not receive their assigned intervention , and 11 ( 1 % ) of 998 participants in the st and ard care group received a home visit or a cryptococcal antigen screen rather than only st and ard care . At 12 months , 25 ( 2 % ) of 1001 participants in the clinic plus community support group and 24 ( 2 % ) of 998 participants in the st and ard care group had been lost to follow-up , and were censored at their last visit for the primary analysis . At 12 months , 134 ( 13 % ) of 1001 participants in the clinic plus community support group had died compared with 180 ( 18 % ) of 998 in the st and ard care group . Mortality was 28 % ( 95 % CI 10 - 43 ) lower in the clinic plus community support group than in st and ard care group ( p=0·004 ) . INTERPRETATION Screening and pre-emptive treatment for cryptococcal infection combined with a short initial period of adherence support after initiation of ART could substantially reduce mortality in HIV programmes in Africa . FUNDING European and Developing Countries Clinical Trials Partnership Background Cryptococcus is the most common cause of adult meningitis in Africa . We evaluated the activity of adjunctive sertraline , previously demonstrated to have in vitro and in vivo activity against Cryptococcus . Methods We enrolled 172 HIV-infected Ug and ans with cryptococcal meningitis from August 2013 through August 2014 into an open-label dose-finding study to assess safety and microbiologic efficacy . Sertraline 100–400mg/day was added to st and ard therapy of amphotericin + fluconazole 800mg/day . We evaluated early fungicidal activity via Cryptococcus cerebrospinal fluid ( CSF ) clearance rate , sertraline pharmacokinetics , and in vitro susceptibility . Findings Participants receiving any sertraline dose averaged a CSF clearance rate of −0·37 ( 95%CI : −0·41 , −0·33 ) colony forming units (CFU)/mL/day . Incidence of paradoxical immune reconstitution inflammatory syndrome ( IRIS ) was 5 % ( 2/43 ) and relapse was 0 % through 12-weeks . Sertraline  reached steady state concentrations in plasma by day 7 , with median steady-state concentrations of 201 ng/mL ( IQR , 90–300 ; n=49 ) with 200mg/day and 399 ng/mL ( IQR , 279–560 ; n=30 ) with 400mg/day . Plasma concentrations reached 83 % of steady state levels by day 3 . The median projected steady state brain tissue concentration at 200mg/day was 3·7 ( IQR , 2·0–5·7 ) mcg/mL and 6·8 ( IQR , 4·6–9·7 ) mcg/mL at 400mg/day . Minimum inhibitory concentrations were ≤2 mcg/mL for 27 % ( 35/128 ) , ≤4 mcg/mL for 84 % ( 108/128 ) , ≤6 mcg/mL for 91 % ( 117/128 ) , and ≤8 mcg/mL for 100 % of 128 Cryptococcus isolates . Interpretation Sertraline  had faster cryptococcal CSF clearance , decreased IRIS , and decreased relapse compared with historical experiences . Sertraline reaches therapeutic levels in a clinical setting . This inexpensive and off-patent oral medication is a promising adjunctive antifungal therapy . Funding National Institutes of Health , Gr and Challenges Canada BACKGROUND Cryptococcal disease remains an important cause of morbidity and mortality in HIV-infected individuals in sub-Saharan Africa , despite the introduction of antiretroviral therapy . We studied fluconazole as primary prophylaxis against cryptococcal disease in patients awaiting or starting antiretroviral therapy in Ug and a. METHODS In this prospect i ve , double-blind r and omised controlled trial , we enrolled HIV-positive adults with CD4 counts less than 200 cells per μL , cryptococcal antigen (CrAg)-negative , naive for antiretroviral therapy , and coming from five local AIDS organisations in Masaka district , Ug and a. Enrolment took place between Sept 14 , 2004 , and Feb 1 , 2008 . Participants were r and omly allocated to placebo or 200 mg fluconazole three times per week ( 1:1 ) in blocks of 40 . R and omisation was done with ralloc procedure in Stata . Participants were review ed after 4 weeks and referred for antiretroviral therapy , then seen every 8 weeks . Participants discontinued trial treatment when CD4 counts reached 200 cells per μL ( median 197 days ) . Primary endpoints were invasive cryptococcal disease and all-cause mortality . Secondary endpoints were time to first episode and incidence of oesophageal c and idosis , time to first episode and incidence of oropharyngeal or vaginal c and idosis , and time to first hospital admission or death . The primary safety endpoint was cessation of trial drug because of transaminase concentrations higher than five times the upper limit of normal ( ULN ) , or other major adverse events . Analyses were done by intention to treat and included all participants enrolled in the trial . Participants and research ers were masked to group assignment . This trial is registered with controlled-trials.com , number IS RCT N 76481529 . RESULTS Of 1519 individuals enrolled , 760 participants received fluconazole and 759 received placebo . 19 developed cryptococcal disease , one in the fluconazole group and 18 in the placebo group ( p=0·0001 ) ; adjusted HR ( aHR ) 18·7 ( 95 % CI 2·5 - 140·7 ) . One case of cryptococcal disease could be prevented by treating 44·6 patients with baseline CD4 counts lower than 200 cells per μL. Fluconazole was effective against cryptococcal disease both before ( aHR=11·0 [ 1·4 - 85·3 ] ) and after start of antiretroviral therapy ( no cases in fluconazole vs seven cases on placebo ) . Seven participants died from cryptococcal disease , none in the fluconazole group . All-cause mortality ( n=189 ) did not differ between the two groups ( p=0·46 ) . Fluconazole  reduced the time to first episode of oesophageal , and oropharyngeal and vaginal c and idosis , as well as the incidence of all c and idosis ( p<0·0001 ) , but had no effect on hospital admission or death . The frequency of elevated transaminases ( > 5 × ULN ) was similar between groups ( aHR=0·94 [ 0·65 - 1·35 ] ) . CONCLUSIONS Fluconazole was safe and effective as primary prophylaxis against cryptococcal disease , both before and during early antiretroviral treatment . Cryptococcal infection was less common than anticipated because of the rapid commencement of antiretroviral therapy and exclusion of those with positive CrAg . In patients with negative CrAg on screening , fluconazole prophylaxis can prevent cryptococcal disease while waiting for and in the early weeks of antiretroviral therapy , particularly in those with CD4 counts of less than 100 cells per μL. FUNDING Medical Research Council , UK , and Rockefeller Foundation The effect of fluconazole prophylaxis on the vaginal flora of 323 human immunodeficiency virus-infected women was evaluated in a multicenter , r and omized , double-blind , placebo-controlled trial . Women with CD4 cell counts of < or = 300/mm3 received either 200 mg of fluconazole per week or placebo .  Vaginal surveillance cultures were performed every 3 months . After a follow-up of 29 months , C and ida albicans was recovered from 53 % of patients receiving fluconazole and 68 % of patients assigned placebo . Fluconazole was associated with a 50 % reduction in the odds of being colonized with C. albicans but with higher rates for non-albicans C and ida species . C and ida glabrata was recovered from 40 women assigned fluconazole and 29 assigned placebo ( relative odds , 1.96 ; 95 % confidence interval , 0.98 - 3.94 ) . Fluconazole had an early and persistent effect on the vaginal mycoflora , with the emergence of C. glabrata vaginal colonization within the first 6 months . The effect of fluconazole prophylaxis can be attributed to the reduction in vaginal C. albicans colonization ; however , C. glabrata colonization rapidly supervened PURPOSE The effects of continuous or intermittent therapy with fluconazole on the recurrence of and the development of fluconazole resistance are not known . PATIENTS AND METHODS We studied human immunodeficiency virus (HIV)-positive patients with CD4 cell count < 350 x 10(6)/L and oropharyngeal c and idiasis in a prospect i ve , r and omized study . After initial treatment , 20 patients ( 16 of whom completed 3 months of follow-up ) received continuous fluconazole at 200 mg/day , and 48 patients ( 28 of whom completed follow-up ) received intermittent therapy at the time of symptomatic relapses . Oral sample s were obtained weekly during episodes of infection and quarterly as surveillance cultures . Development of resistance was defined as a fourfold rise in minimum inhibitory concentration ( MIC ) to at least 16 microg/mL from the initial culture in the same species , the emergence of new , resistant ( MIC > or = 16 microg/mL ) species , or a significant increase in the proportion of resistant isolates . RESULTS During a mean follow-up of 11 months , median annual relapse rates were lower in patients on continuous therapy ( 0 episodes/year ) than in patients on intermittent therapy ( 4.1 episodes/year ; P < 0.001 ) . Sterile cultures were seen in 6 of 16 ( 38 % ) patients on continuous therapy compared with 3 of 28 ( 11 % ) on intermittent therapy ( P = 0.04 ) . Microbiological resistance developed in 9 of 16 ( 56 % ) patients on continuous treatment , compared with 13 of 28 ( 46 % ) on intermittent treatment ( P = 0.75 ) . However , despite isolates with increased MICs , 42 of 44 patients responded to fluconazole in doses up to 800 mg/day . CONCLUSIONS In patients with frequent recurrences , continuous suppressive therapy significantly reduced relapses and colonization . Resistance occurred with both continuous and intermittent therapy ; however , therapeutic responses were excellent BACKGROUND In human immunodeficiency virus (HIV)-infected patients , fluconazole prophylaxis is associated with reductions in the rate of fungal infection . However , concerns exist with regard to the use of fluconazole prophylaxis and the risk of development of fluconazole treatment-refractory infections . METHODS We performed a r and omized , open-label trial that compared oral fluconazole given continuously ( 200 mg 3 times weekly ; the " continuous fluconazole arm " ) with fluconazole that was provided only for episodes of orophaynge 
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Authors ' conclusions Antifungal prophylaxis reduced the risk of developing and dying from cryptococcal disease .
Therefore , where CrAG screening is not available , antifungal prophylaxis may be used in patients with low CD4 counts at diagnosis and who are at risk of developing cryptococcal disease