***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 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 Introduction : We explored factors associated with differential HIV incidence among women participating in a HIV prevention trial in Harare , Durban , and Johannesburg . The trial had shown no effect of the intervention ( diaphragm and lubricant gel ) on HIV incidence . Methods : A prospect i ve cohort analysis was conducted of trial participants followed for 12 - 24 months . Sociodemographic , biological , and behavioral data were collected at baseline and at quarterly visits . Factors associated with HIV incidence were estimated using multivariable Cox regression models , stratified by study location . Attributable risk was calculated from the adjusted hazard ratios ( AHR ) . Results : There were 309 incident HIV infections among the 4948 women in the analysis .  HIV incidence was highest in Durban [ 6.75/100 person-years ; 95 % confidence interval ( CI ) : 5.74 to 7.93 ] , lower in Johannesburg ( 3.33/100 person-years ; 95 % CI : 2.51 to 4.44 ) , and lowest in Harare ( 2.72/100 person-years ; 95 % CI : 2.26 to 3.26 ) . Sexually transmitted infections were important risk factors in Harare [ prevalent herpes simplex virus type 2 ( HSV2 ) AHR = 2.56 , 95 % CI : 1.61 to 4.06 ; incident HSV2 AHR = 12.60 , 95 % CI : 2.13 to 21.87 ; Neisseria gonorrhoeae AHR = 6.82 , 95 % CI : 2.13 to 21.87 ] and in Durban ( prevalent HSV2 AHR = 1.64 , 95 % CI : 1.07 to 2.51 ; N. gonorrhoeae AHR = 4.40 , 95 % CI : 2.07 to 9.39 ) . In Durban , having multiple partners ( adjusted odds ratio ( AOR ) = 1.78 95 % CI : 1.11 to 2.85 ) and sex although a partner was under the influence of alcohol/drugs ( AOR = 1.51 95 % CI : 1.05 to 2.16 ) significantly increased risk , whereas in Johannesburg , sexual debut < 16 years ( AOR = 2.60 95 % CI : 1.30 to 5.17 ) was a strong predictor of HIV acquisition . Discussion : Important differences were seen in drivers of HIV incidence at the 3 study locations . Results from this analysis imply that targeted HIV programing could have a large impact on incident HIV infection in women , and that the most effective approach will likely vary based on knowledge of the local situation/epidemiology We examined  condom breakage rates and predictors of breakage in a prospect i ve telephone-based study of female sex workers ( FSWs ) in Bangalore , India . We obtained data on 3,257 condom-use sex acts , and breakage occurred in 2.1 % of these . Situational factors , especially those associated with male clients ’ behaviors , were the most important predictors of breakage , including sexual inexperience , roughness and violence . Breakage was also associated with having vaginal and anal sex at the same encounter and with poor-fitting condoms . Despite lower than expected breakage rates , the high client volume of FSWs means that there are many unprotected sex acts caused by breakage . Discussion s should be held around new education messages , and how programs can respond quickly when sex workers encounter clients who are inebriated , violent or unusually sexually charged . More work is urgently needed with police , and on FSW empowerment , the use of help lines , and counseling for the most vulnerable women HIV seroconversion outcomes in preexposure prophylaxis ( PrEP ) trials of oral tenofovir (TFV)-containing regimens are highly sensitive to drug concentration , yet less-than-daily dosing regimens are under study . Description of TFV and its active moiety , TFV diphosphate ( TFV-DP ) , in blood , vaginal tissue , and colon tissue may guide the design and interpretation of PrEP clinical trials . Six healthy women were administered a single oral dose of 300 mg tenofovir disoproxil fumarate ( TDF ) and 4.3 mg ( 12.31 MBq , 333 μCi ) (14)C-TDF slurry . Blood was collected every 4 h for the first 24 h , then at 4 , 8 , 11 , and 15 days postdosing . Colonic and vaginal sample s ( tissue , total and CD4(+ ) cells , luminal fluid and cells ) were collected 1 , 8 and 15 days postdose . Sample s were analyzed for TFV and TFV-DP . Plasma TFV demonstrated triphasic decay with terminal elimination half-life median [ interquartile range ( IQR ) ] 69 h ( 58 - 77 ) . Peripheral blood mononuclear cell ( P BMC ) TFV-DP demonstrated biphasic peaks ( median 12 h and 96 h ) followed by a terminal 48 h ( 38 - 76 ) half-life ; Cmax was 20 fmol/million cells ( 2 - 63 ) . One day postdose , the TFV-DP paired colon : vaginal tissue concentration ratio was 1 or greater in all subjects ' tissue homogenates , median 124 ( range 1 - 281 ) , but was not sustained . The ratio was lower and more variable in cells extracted from tissue . Among all sample types , TFV and TFV-DP half-life ranged from 23 to 139 h. P BMC TFV-DP rose slowly in the hours after dosing indicating that success with exposure-driven dosing regimens may be sensitive to timing of the dose prior to exposure . Colonic tissue homogenate TFV-DP concentrations were greater than in vaginal homogenate at 24 h , but not in cells extracted from tissue . These and the other pharmacokinetic findings will guide the interpretation and design of future PrEP trials BACKGROUND Reproductive-age women need effective interventions to prevent the acquisition of  human immunodeficiency virus type 1 ( HIV-1 ) infection . METHODS We conducted a r and omized , placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate ( TDF ) , oral tenofovir-emtricitabine ( TDF-FTC ) , or 1 % tenofovir ( TFV ) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa , Ug and a , and Zimbabwe .  HIV-1 testing was performed monthly , and plasma TFV levels were assessed quarterly . RESULTS Of 12,320 women who were screened , 5029 were enrolled in the study . The rate of retention in the study was 91 % during 5509 person-years of follow-up . A total of 312 HIV-1 infections occurred ; the incidence of HIV-1 infection was 5.7 per 100 person-years . In the modified intention-to-treat analysis , the effectiveness was -49.0 % with TDF ( hazard ratio for infection , 1.49 ; 95 % confidence interval [ CI ] , 0.97 to 2.29 ) , -4.4 % with TDF-FTC ( hazard ratio , 1.04 ; 95 % CI , 0.73 to 1.49 ) , and 14.5 % with TFV gel ( hazard ratio , 0.85 ; 95 % CI , 0.61 to 1.21 ) . In a r and om sample , TFV was detected in 30 % , 29 % , and 25 % of available plasma sample s from participants r and omly assigned to receive TDF , TDF-FTC , and TFV gel , respectively . Independent predictors of TFV detection included being married , being older than 25 years of age , and being multiparous . Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition . Elevations of serum creatinine levels were seen more frequently among participants r and omly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo ( 1.3 % vs. 0.2 % , P=0.004 ) . We observed no significant differences in the frequencies of other adverse events . CONCLUSIONS None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis . Adherence to study drugs was low . ( Funded by the National Institutes of Health ; VOICE Clinical Trials.gov number , NCT00705679 . ) Vaginal Gel Versus HIV HIV prevention technologies for women are urgently needed , especially in sub-Saharan Africa where young women bear the greatest burden of the HIV epidemic . Abdool Karim et al. ( p. 1168 ; published online 19 July ) present the results of the CAPRISA 004 r and omized control trial . The nearly 3-year-long trial , conducted in urban and rural South African women , tested the efficacy of a vaginal gel containing the antiretroviral drug tenofovir in preventing HIV infection . The dosing strategy required application of the gel both before and after coitus , and with this regime HIV infection was reduced by approximately 39 % overall , by 54 % in women with high adherence to the protocol , and with no increase in overall adverse event rates . Tenofovir in a vaginal gel formulation shows significant protection against HIV infection in a r and omized control trial . The Centre for the AIDS Program of Research in South Africa ( CAPRISA ) 004 trial assessed the effectiveness and safety of a 1 % vaginal gel formulation of tenofovir , a nucleotide reverse transcriptase inhibitor , for the prevention of HIV acquisition in women . A double-blind , r and omized controlled trial was conducted comparing  tenofovir gel ( n = 445 women ) with  placebo gel ( n = 444 women ) in sexually active , HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal , South Africa .  HIV serostatus , safety , sexual behavior , and gel and condom use were assessed at monthly follow-up visits for  
    Output:
    
AI acts were as likely to be condom protected as vaginal acts .