***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 Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus ( HIV ) among men who have sex with men ; however , the efficacy among heterosexuals is uncertain . METHODS We r and omly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or matching placebo once daily . Monthly study visits were scheduled , and participants received a comprehensive package of prevention services , including HIV testing , counseling on adherence to medication , management of sexually transmitted infections , monitoring for adverse events , and individualized counseling on risk reduction ; bone mineral density testing was performed semiannually in a subgroup of participants . RESULTS A total of 1219 men and women underwent r and omization ( 45.7 % women ) and were followed for 1563 person-years ( median , 1.1 years ; maximum , 3.7 years ) . Because of low retention and logistic limitations , we concluded the study early and followed enrolled participants through an orderly study closure rather than exp and ing enrollment . The TDF-FTC group had higher rates of nausea ( 18.5 % vs. 7.1 % , P<0.001 ) , vomiting ( 11.3 % vs. 7.1 % , P=0.008 ) , and dizziness ( 15.1 % vs. 11.0 % , P=0.03 ) than the placebo group , but the rates of serious adverse events were similar ( P=0.90 ) . Participants who received TDF-FTC , as compared with those who received placebo , had a significant decline in bone mineral density . K65R , M184V , and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment . In a modified intention-to-treat analysis that included the 33 participants who became infected during the study ( 9 in the TDF-FTC group and 24 in the placebo group ; 1.2 and 3.1 infections per 100 person-years , respectively ) , the efficacy of TDF-FTC was 62.2 % ( 95 % confidence interval , 21.5 to 83.4 ; P=0.03 ) . CONCLUSIONS Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults . The long-term safety of daily TDF-FTC prophylaxis , including the effect on bone mineral density , remains unknown . ( Funded by the Centers for Disease Control and Prevention and the National Institutes of Health ; TDF2 Clinical Trials.gov number , NCT00448669 . ) Background Efficacy of oral pre-exposure prophylaxis ( PrEP ) in prevention of HIV acquisition has been evaluated using a daily regimen . However , adherence to long term daily medication is rarely perfect . Intermittent regimen may be a feasible alternative . Pre clinical studies have demonstrated effectiveness of intermittent PrEP in SHIV prevention among animals . However , little is known about intermittent PrEP regimens . Design Seventy two HIV-uninfected volunteers in HIV serodiscordant couple relationships in Ug and a were r and omly assigned to receive daily oral Tenofovir/Emtricitabine ( TDF/FTC-Truvada ) or placebo , or intermittent ( Monday , Friday and within 2 hours after sex , not to exceed one dose per day ) oral TDF/FTC or placebo in a 2:1:2:1 ratio . Volunteers and study staff were blinded to drug assignment , but not to regimen assignment . Methods Volunteers were followed for 4 months after r and omization , with monthly clinical and laboratory safety assessment s and comprehensive HIV risk reduction services . Adherence was monitored using medication event monitoring system ( MEMS ) and self-report . Sexual activity data were collected via daily short text message ( SMS ) and self-report . HIV-specific immune responses were assessed by IFN-γ ELISPOT . Results Both daily and intermittent oral TDF/FTC regimens were well tolerated . Median MEMS adherence rates were 98 % ( IQR : 93 - 100 ) for daily PrEP regimen , 91 % ( IQR : 73 - 97 ) for fixed intermittent dosing and 45 % ( IQR : 20 - 63 ) for post-coital dosing . SMS response rate was 74 % , but increased to 80 % after excluding server outages ; results may have been affected by the novelty of this measure . The majority of volunteers expressed willingness with no particular preference for either regimen . Conclusions Both daily and intermittent oral PrEP dosing regimens were safe . Adherence was high for daily and fixed intermittent dosing ; post-coital dosing was associated with poor adherence . Fixed intermittent PrEP regimens may be feasible especially if a minimum effective drug concentration correlating with HIV prevention can be achieved with this dosing . Registration Clinical trials.gov number Background Safety of tenofovir disoproxil fumarate/emtricitabine ( TDF-FTC ) has been studied more extensively among HIV-infected patients than among HIV-uninfected people . Using data from a pre-exposure trial – FEM-PrEP – , we determined the cumulative probabilities of grade 1 + ALT , AST and creatinine and grade 2 + phosphorus toxicities ; ALT/AST toxicities by baseline hepatitis B status ; and change in mean creatinine , phosphorus , ALT and AST levels controlling for TDF-FTC adherence . Methods and findings FEM-PrEP was a r and omized , blinded , placebo-controlled trial of daily TDF-FTC among women in Africa . Enrolled women were in general good health , HIV antibody negative , 18 to 35 years old , hepatitis B surface antigen negative , and had normal hepatic and renal function at baseline .  AST , ALT , phosphorus and serum creatinine were measured regularly throughout the trial . TDF-FTC concentrations were measured to assess adherence to TDF-FTC . The cumulative probabilities of grade 1 + creatininemia and grade 2 + phosphatemia toxicities were not statistically different between TDF-FTC and placebo arms . The cumulative probabilities of grade 1 + ALT and AST toxicities were higher among participants in the TDF-FTC arm than in the placebo arm ( p = 0.03 for both ) . The proportions of grade 1 + and grade 2 + ALT or AST toxicities were significantly higher in participants who were hepatitis B virus surface antibody ( HBsAb ) positive than in those who were HBsAb-negative . Women with good adherence had higher mean change from baseline to week 4 in their AST levels ( 2.90 ( 0.37 , 5.42 ) ; p = 0.025 ) than women with less than good adherence . Conclusions We did not observe a significant relationship between r and omization to TDF-FTC and creatinine or phosphorus toxicities . Women r and omized to TDF-FTC had higher rates of mild to moderate ALT/AST toxicities , especially women with prior hepatitis B virus exposure . We also observed a significant increase in AST from baseline to week 4 among women who had higher adherence to TDF-FTC during that interval . Trial register#NCT00625404 , February 19 , 2008 Background Little is known about safety of and adherence to intermittent HIV PrEP regimens , which may be more feasible than daily dosing in some setting s. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men ( MSM ) and female sex workers ( FSW ) . Methods /Principal Findings MSM and FSW were r and omized to daily oral FTC/TDF or placebo , or intermittent ( Monday , Friday and within 2 hours after sex , not to exceed one dose per day ) oral FTC/TDF or placebo in a 2∶1∶2∶1 ratio ; volunteers were followed monthly for 4 months . Adherence was assessed with the medication event monitoring system ( MEMS ) . Sexual activity data were collected via daily text message ( SMS ) queries and timeline followback interviews with a one-month recall period . Sixty-seven men and 5 women were r and omized into the study .  Safety was similar among all groups . Median MEMS adherence rates were 83 % [ IQR : 63–92 ] for daily dosing and 55 % [ IQR:28–78 ] for fixed intermittent dosing ( p = 0.003 ) , while adherence to any post-coital doses was 26 % [ IQR:14–50 ] . SMS response rates were low , which may have impaired measurement of post-coital dosing adherence . Acceptability of PrEP was high , regardless of dosing regimen . Conclusions / Significance Adherence to intermittent dosing regimens , fixed doses , and in particular coitally-dependent doses , may be more difficult than adherence to daily dosing . However , intermittent dosing may still be appropriate for PrEP if intracellular drug levels , which correlate with prevention of HIV acquisition , can be attained with less than daily dosing and if barriers to adherence can be addressed . Additional drug level data , qualitative data on adherence barriers , and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more st and ard regimens . Trial Registration Clinical Trials.gov BACKGROUND For maximum effect pre-exposure prophylaxis should be targeted to the sub population s that account for the largest proportion of infections ( population -attributable fraction [ PAF ] ) and for whom the number needed to treat ( NNT ) to prevent infection is lowest . We aim ed to estimate the PAF and NNT of participants in the iPrEx ( Pre-Exposure Prophylaxis Initiative ) trial . METHODS The iPrEx study was a r and omised controlled efficacy trial of pre-exposure prophylaxis with coformulated tenofovir disoproxil fumarate and emtricitabine in 2499 men who have sex with men ( MSM ) and transgender women . Participants aged 18 years or older who were male at birth were enrolled from 11 trial sites in Brazil , Ecuador , Peru , South Africa , Thail and , and the USA . Participants were r and omly assigned ( 1:1 ) to receive either a pill with active pre-exposure prophylaxis or placebo , taken daily . We calculated the association between demographic and risk behaviour during screening and subsequent seroconversion among placebo recipients using a Poisson model , and we calculated the PAF and NNT for risk behaviour subgroups . The iPrEx trial is registered with Clinical Trials.gov , NCT00458393 . FINDINGS Patients were enrolled between July 10 , 2007 , and Dec 17 , 2009 , and were followed up until Nov 21 , 2010 . Of the 2499 MSM and transgender women in the iPrEx trial , 1251 were assigned to pre-exposure prophylaxis and 1248 to placebo . 83 of 1248 patients in the placebo group became infected with HIV during follow-up . Participants reporting receptive anal intercourse without a condom seroconverted significantly more often than those reporting no anal sex without a condom ( adjusted hazard ratio [ AHR ] 5·11 , 95 % CI 1·55 - 16·79 ) . The overall PAF for MSM and transgender women reporting receptive anal intercourse without a condom was 64 % ( prevalence 60 % ) . Most of this risk came from receptive anal intercourse without a condom with partners with unknown serostatus ( PAF 53 % , prevalence 54 % , AHR 4·76 , 95 % CI 1·44 - 15·71 ) ; by contrast , the PAF for receptive anal intercourse without a condom with an HIV-positive partner was 1 % ( prevalence 1 % , AHR 7·11 , 95 % CI 0·70 - 72·75 ) . The overall NNT per year for the cohort was 62 ( 95 % CI 44 - 147 ) . NNTs were lowest for MSM and transgender women self-reporting receptive anal intercourse without a condom ( NNT 36 ) , cocaine use ( 12 ) , or a sexually transmitted infection ( 41 ) . Having one partner and insertive anal sex without a condom had the highest NNTs ( 100 and 77 , respectively ) . INTERPRETATION Pre-exposure prophylaxis may be most effective at a population level if targeted toward MSM and transgender women who report receptive anal intercourse without a condom , even if they perceive their partners to be HIV negative . Substance use history and testing for STIs should also inform individual decisions to start pre-exposure prophylaxis . Consideration of the PAF and NNT can aid in discussion of the benefits and risks of pre-exposure prophylaxis with MSM and transgender women . FUNDING National Institute of Allergy and Infectious Diseases and the Bill & Melinda Gates Foundation BACKGROUND Antiretroviral pre-exposure prophylaxis reduces sexual transmission of HIV . We assessed whether daily oral use of tenofovir disoproxil fumarate ( tenofovir ) , an antiretroviral , can reduce HIV transmission in injecting drug users . METHODS In 
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RESULTS Eighteen studies were included , comprising data from 39 articles and six conference abstract s. Across population s and PrEP regimens , PrEP significantly reduced the risk of HIV acquisition compared with placebo .
Trials with low PrEP use did not show a significantly protective effect .
Adverse events were similar between PrEP and placebo groups .
More cases of drug-resistant HIV infection were found among  PrEP users who initiated PrEP while acutely HIV-infected , but incidence of acquiring drug-resistant HIV during PrEP use was low .
Studies consistently found no association between  PrEP  use and changes in sexual risk behavior .
PrEP was not associated with increased pregnancy-related adverse events or hormonal contraception effectiveness .
CONCLUSION PrEP is protective against HIV infection across population s , presents few significant safety risks , and there is no evidence of behavioral risk compensation .