***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*** 
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    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 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 This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa , Kenya , who used oral pre-exposure prophylaxis ( PrEP ) for HIV prevention as part of a four-month trial of safety , acceptability and adherence . Fifty-one of 72 volunteers who took part in a r and omized , placebo-controlled , blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessment s after completing the trial . Analyses identified three themes : ( i ) acceptability of PrEP  was high , i.e. side effects were experienced early in the study but diminished over time , however characteristics of pills could improve comfort and use ; ( ii ) social impacts such as stigma , rumors , and relationship difficulties due to being perceived as HIV positive were prevalent ; ( iii ) adherence was challenged by complexities of daily life , in particular post-coital dosing adherence suffered from alcohol use around time of sex , mobile population s , and transactional sex work . These themes resonated across dosing regimens and gender , and while most participants favored the intermittent dosing schedule , those in the intermittent group noted particular challenges in adhering to the post-coital dose . Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness Background In VOICE , a multisite HIV pre-exposure prophylaxis ( PrEP ) trial , plasma drug levels pointed to widespread product nonuse , despite high adherence estimated by self-reports and clinic product counts . Using a socio-ecological framework ( SEF ) , we explored socio-cultural and context ual factors that influenced participants ’ experience of daily vaginal gel and oral tablet regimens in VOICE . Methods In Johannesburg , a qualitative ancillary study was concurrently conducted among r and omly selected VOICE participants assigned to in-depth interviews ( n = 41 ) , serial ethnographic interviews ( n = 21 ) , or focus group discussion s ( n = 40 ) . Audiotaped interviews were transcribed , translated , and coded thematically for analysis . Results Of the 102 participants , the mean age was 27 years , and 96 % had a primary sex partner with whom 43 % cohabitated . Few women reported lasting nonuse , which they typically attributed to missed visits , lack of product replenishments , and family-related travel or work . Women acknowledged occasionally skipping or mistiming doses because they forgot , were busy , felt lazy or bored , feared or experienced side effects . However , nearly all knew or heard of other study participants who did not use products daily . Three overarching themes emerged from further analyses : ambivalence toward research , preserving a healthy status , and managing social relationships . These themes highlighted the profound and complex meanings associated with participating in a blinded HIV PrEP trial and taking antiretroviral-based products . The unknown efficacy of products , their connection with HIV infection , challenges with daily regimen given social risks , lack of support – from partners and significant others– and the relationship tradeoffs entailed by using the products appear to discourage adequate product use . Conclusions Personal acknowledgment of product nonuse was challenging . This qualitative inquiry highlighted key influences at all SEF levels that shaped women ’s perceptions of trial participation and experiences with investigational products . Whether these impacted women ’s behaviors and may have contributed to ineffective trial results warrants further investigation Summary Background R and omised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis ( PrEP ) with tenofovir – emtricitabine reduces the risk of HIV infection . However , this benefit could be counteracted by risk compensation in users of PrEP . We did the PROUD study to assess this effect . Methods PROUD is an open-label r and omised trial done at 13 sexual health clinics in Engl and . We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days . Participants were r and omly assigned ( 1:1 ) to receive daily combined tenofovir disoproxil fumarate ( 245 mg ) and emtricitabine ( 200 mg ) either immediately or after a deferral period of 1 year . R and omisation was done via web-based access to a central computer-generated list with variable block sizes ( stratified by clinical site ) . Follow-up was quarterly . The primary outcomes for the pilot phase were time to accrue 500 participants and retention ; secondary outcomes included incident HIV infection during the deferral period , safety , adherence , and risk compensation . The trial is registered with IS RCT N ( number IS RCT N94465371 ) and Clinical Trials.gov ( NCT02065986 ) . Findings We enrolled 544 participants ( 275 in the immediate group , 269 in the deferred group ) between Nov 29 , 2012 , and April 30 , 2014 . Based on early evidence of effectiveness , the trial steering committee recommended on Oct 13 , 2014 , that all deferred participants be offered PrEP . Follow-up for HIV incidence was complete for 243 ( 94 % ) of 259 patient-years in the immediate group versus 222 ( 90 % ) of 245 patient-years in the deferred group . Three HIV infections occurred in the immediate group ( 1·2/100 person-years ) versus 20 in the deferred group ( 9·0/100 person-years ) despite 174 prescriptions of post-exposure prophylaxis in the deferred group ( relative reduction 86 % , 90 % CI 64–96 , p=0·0001 ; absolute difference 7·8/100 person-years , 90 % CI 4·3–11·3 ) . 13 men ( 90 % CI 9–23 ) in a similar population would need access to 1 year of PrEP to avert one HIV infection . We recorded no serious adverse drug reactions ; 28 adverse events , most commonly nausea , headache , and arthralgia , result ed in interruption of PrEp . We detected no difference in the occurrence of sexually transmitted infections , including rectal gonorrhoea and chlamydia , between groups , despite a suggestion of risk compensation among some PrEP recipients . Interpretation In this high incidence population , daily tenofovir – emtricitabine conferred even higher protection against HIV than in placebo-controlled trials , refuting concerns 
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Results Adherence varied between differing population s both geographically and socioeconomically .
Common reasons for non-adherence reported over multiple studies were ; social factors such as stigma , low risk perception , low decision making power , an unacceptable dosing regimen , side effects , and the logistics of daily life .
Oral pre-exposure prophylaxis with included antiviral regimens was not associated with a high risk of antiviral resistance development in the review ed studies .
Conclusion Our findings indicate that oral pre-exposure prophylaxis should be delivered within a holistic intervention , acknowledging the other needs of the targeted demographic in order to maximise acceptability .
Socioeconomic factors and poor governmental policy remain major barriers to widespread implementation of pre-exposure prophylaxis