***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: Objective : To investigate HIV incidence during a trial of two voluntary counselling and testing ( VCT ) strategies . Counselling may promote beneficial behavioural change , although knowledge of negative status does not appear to contribute further benefit . Design : The parent cluster-r and omized trial demonstrated much greater uptake of VCT when counselling and rapid testing were available on-site ( intensive VCT ) than through pre-paid vouchers to an external provider ( st and ard VCT ) . Anonymous HIV tests had been requested from all employees at enrolment and after 2 years intervention . Methods : The study setting was 22 businesses in Harare , Zimbabwe . Participants were 3146 HIV-negative individuals remaining in employment at the end of intervention , of whom 2966 ( 94.3 % ) consented to repeat testing . VCT linked to basic HIV care was provided and the main outcome measures were HIV incidence under each study arm , as a retrospective secondary analysis . Results : Mean VCT uptake in this cohort was 70.7 and 5.2 % , respectively , in the intensive and st and ard arms . Crude HIV incidence was 1.21 per 100 person-years , with non-significantly higher rates in the intensive VCT arm [ mean site incidence 1.37 and 0.95 per 100 person-years , respectively ; adjusted rate ratio 1.49 ( 95 % confidence interval 0.79–2.80 ) . Conclusions : Highly acceptable VCT did not reduce HIV incidence in this predominantly male cohort .  HIV incidence was highest in the high uptake VCT arm , lending support to a US trial in which rapid testing appeared to have adverse behavioural consequences in some HIV-negative clients . Careful comparison of outcomes under different counselling and testing strategies is needed to maximize HIV prevention from global scale-up of VCT Objective The objective of this trial was to determine the effectiveness of 1.0 % C31 G ( SAVVY ) in preventing male-to-female vaginal transmission of HIV infection among women at high risk . Methodology /Principal Findings This was a Phase 3 , double-blind , r and omized , placebo-controlled trial . Participants made up to 12 monthly visits for HIV testing , adverse event reporting , and study product supply . The study was conducted between March 2004 and February 2006 in Accra and Kumasi , Ghana . We enrolled 2142 HIV-negative women at high risk of HIV infection , and r and omized them to SAVVY or placebo gel . Main outcome measures were the incidence of HIV-1 and HIV-2 infection as determined by detection of HIV antibodies from oral mucosal transu date specimens and adverse events . We accrued 790 person-years of follow-up in the SAVVY group and 772 person-years in the placebo group . No clinical ly significant differences in the overall frequency of adverse events , abnormal pelvic examination findings , or abnormal laboratory results were seen between treatment groups . However , more participants in the SAVVY group reported reproductive tract adverse events than in the placebo group ( 13.0 % versus 9.4 % ) . Seventeen HIV seroconversions occurred ; eight in participants r and omized to SAVVY and nine in participants receiving placebo . The Kaplan-Meier estimates of the cumulative probability of HIV infection through 12 months were 0.010 in the SAVVY group and 0.011 in the placebo group ( p = 0.731 ) , with a hazard ratio ( SAVVY versus placebo ) of 0.88 ( 95 % confidence interval 0.33 , 2.27 ) . Because of a lower-than-expected HIV incidence , we were unable to achieve the required number of HIV infections ( 66 ) to obtain the desired study power . Conclusions / Significance SAVVY was not associated with increased adverse events overall , but was associated with higher reporting of reproductive adverse events . Our data are insufficient to conclude whether SAVVY is effective at preventing HIV infection relative to placebo . Trial Registration Clinical Trials.gov BACKGROUND Female-initiated HIV-prevention options , such as microbicides , are urgently needed . We assessed Carraguard , a carrageenan-based compound developed by the Population Council , for its efficacy and long-term safety in prevention of HIV infection in women . METHODS We undertook a r and omised , placebo-controlled , double-blind trial in three South African sites in sexually-active , HIV-negative women , aged 16 years and older . 6202 participants , who were r and omly assigned by a block r and omisation scheme to Carraguard ( n=3103 ) or placebo ( methylcellulose [ n=3099 ] ) , were instructed to use one applicator of gel plus a condom during each vaginal sex act . Participants were followed up for up to 2 years . Visits every 3 months included testing for HIV presence and pregnancy , pelvic examinations , risk reduction counselling , and treatment for curable sexually transmitted infections and symptomatic vaginal infections . The primary outcome was time to HIV seroconversion . Analysis was in the efficacy population ( a subset of the intention-to-treat population , excluding participants for whom efficacy could not be assessed ) . This study is registered with Clinical Trials.gov , number NCT00213083 . FINDINGS For the primary outcome ( time to HIV seroconversion ) we analysed 3011 women in the Carraguard group and 2994 in the placebo group .  HIV incidence was 3.3 per 100 woman-years ( 95 % CI 2.8 - 3.9 ) in the Carraguard group ( 134 events ) and 3.8 per 100 woman-years ( 95 % CI 3.2 - 4.4 ) in the placebo group ( 151 events ) , with no significant difference in the distribution of time to seroconversion ( p=0.30 ) . The covariate-adjusted hazard ratio was 0.87 ( 95 % CI 0.69 - 1.09 ) . Rates of self-reported gel use ( 96.2 % Carraguard , 95.9 % placebo ) and condom use ( 64.1 % in both groups ) at last sex acts were similar in both groups . On the basis of applicator testing , however , gel was estimated to have been used in only 42.1 % of sex acts , on average ( 41.1 % Carraguard , 43.1 % placebo ) . 1420 ( 23 % ) women in the intention-to-treat population had adverse events ( 713 Carraguard , 707 placebo ) , and 95 ( 2 % ) women had adverse events that were related to gel use ( 48 Carraguard , 47 placebo ) . Serious adverse events occurred in 72 ( 2 % ) women in the Carraguard group and 78 ( 3 % ) in the placebo group , only one of which was considered possibly related to gel use ( placebo group ) . INTERPRETATION This study did not show Carraguard 's efficacy in prevention of vaginal transmission of HIV . No safety concerns were recorded A r and omised trial was done to evaluate the impact of improved sexually transmitted disease ( STD ) case management at primary health care level on the  incidence of HIV infection in the rural Mwanza region of Tanzania .  HIV incidence was compared in six intervention communities and six pair-matched comparison communities . A r and om cohort of about 1000 adults aged 15 - 54 years from each community was surveyed at baseline and at follow-up 2 years later . Intervention consisted of establishment of an STD reference clinic , staff training , regular supply of drugs , regular supervisory visits to health facilities , and health education about STDs .  12,537 individuals were recruited .  Baseline HIV prevalences were 3.8 % and 4.4 % in the intervention and comparison communities , respectively . At follow-up , 8845 ( 71 % ) of the cohort were seen . Of those initially seronegative , the proportions seroconverting over 2 years were 48 of 4149 ( 1.2 % ) in the intervention communities and 82 of 4400 ( 1.9 % ) in the comparison communities . HIV incidence was consistently lower in the intervention communities in all six matched pairs . Allowing for the community-r and omised design and the effects of confounding factors , the estimated risk ratio was 0.58 ( 95 % CI 0.42 - 0.79 , p = 0.007 ) . No change in reported sexual behaviour was observed in either group . We conclude that improved STD treatment reduced HIV incidence by about 40 % in this rural population . This is the first r and omised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population BACKGROUND Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication . The Step Study directly assessed the efficacy of a cell-mediated immunity vaccine to protect against  HIV-1 infection or change in early plasma HIV-1 levels . METHODS We undertook a double-blind , phase II , test-of-concept study at 34 sites in North America , the Caribbean , South America , and Australia . We r and omly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine  ( n=1494 ) or placebo  ( n=1506 ) . R and omisation was prestratified by sex , adenovirus type 5 ( Ad5 ) antibody titre at baseline , and study site . Primary objective was a reduction in HIV-1 acquisition rates ( tested every 6 months ) or a decrease in HIV-1 viral-load setpoint ( early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis ) . Analyses were per protocol and modified intention to treat . The study was stopped early because it unexpectedly met the prespecified futility boundaries at the first interim analysis . This study is registered with Clinical Trials.gov , number NCT00095576 . FINDINGS In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less , 24 ( 3 % ) of 741 vaccine recipients became HIV-1 infected versus 21 ( 3 % ) of 762 placebo recipients ( hazard ratio [ HR ] 1.2 [ 95 % CI 0.6 - 2.2 ] ) . All but one infection occurred in men . The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients ( 4.61 vs 4.41 log(10 ) copies per mL , one tailed p value for potential benefit 0.66 ) . The vaccine elicited interferon-gamma ELISPOT responses in 75 % ( 267 ) of the 25 % r and om sample of all vaccine recipients ( including both low and high Ad5 antibody titres ) on whose specimens this testing was done ( n=354 ) . In exploratory analyses of all study volunteers , irrespective of baseline Ad5 antibody titre , the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men ( HR 2.3 [ 95 % CI 1.2 - 4.3 ] ) and uncircumcised men ( 3.8 [ 1.5 - 9.3 ] ) , but was not increased in Ad5 seronegative ( 1.0 [ 0.5 - 1.9 ] ) or circumcised ( 1.0 [ 0.6 - 1.7 ] ) men . INTERPRETATION This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level . Mechanisms for insufficient efficacy of the vaccine and the increased HIV-1 infection rates in subgroups of vaccine recipients are being explored Background Only four out of 31 completed r and omized controlled trials ( RCTs ) of HIV prevention strategies against sexual transmission have shown significant efficacy . Poor adherence may have contributed to the lack of effect in some of these trials . In this paper we explore the impact of various levels of adherence on measured efficacy within an RCT . Analysis We used simple quantitative methods to illustrate the impact of various levels of adherence on measured efficacy by assuming a uniform population in terms of sexual behavior and the binomial model for the transmission probability per partnership . At 100 % adherence the measured efficacy within an RCT is a reasonable approximation of the true biological efficacy . However , as adherence levels fall , the efficacy measured within a trial substantially under-estimates the true biological efficacy . For example , at 60 % adherence , the measured efficacy can be less than half of the true biological efficacy . Conclusion Poor adherence during a trial can substantially reduce the power to detect an effect , and improved methods of achieving and maintaining high adherence within trials are needed . There are currently 12 ongoing HIV prevention trials , all but one of which require ongoing user-adherence . Attention must be given to methods of maximizing adherence when piloting and design ing RCTs and HIV prevention programmes BACKGROUND Effective interventions are needed to prevent acquisition of HIV infection in men who have sex with men . To date , no behavioural interventions specifically for this risk group have been tested with HIV infection as the primary outcome . METHODS This multisite two-group r and omised controlled phase IIb trial 
    Output:
    
Almost 90 % of HIV prevention trials had ' flat ' results , which may be attributable to trial design and /or implementation .