***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 A novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic ( PK ) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus ( HIV ) preexposure prophylaxis ( PrEP ) . METHODS A PK/pharmacodynamic ( PD ) model was developed by measuring mucosal tissue concentrations of tenofovir , emtricitabine , their active metabolites ( tenofovir diphosphate [ TFVdp ] and emtricitabine triphosphate [ FTCtp ] , respectively ) , and competing endogenous nucleotides ( dATP and dCTP ) in 47 healthy women . TZM-bl and CD4(+ ) T cells were used to identify 90 % effective concentration ( EC90 ) ratios of TFVdp to dATP and FTCtp to dCTP ( alone and in combination ) for protection against HIV . Monte-Carlo simulations were then performed to identify minimally effective dosing strategies to protect lower female genital tract and colorectal tissues . RESULTS The colorectal TFVdp concentration was 10 times higher than that in the lower female genital tract , whereas concentrations of endogenous nucleotides were 7 - 11 times lower . Our model predicted that ≥98 % of the population achieved protective mucosal tissue exposure by the third daily dose of tenofovir disoproxil fumarate plus emtricitabine . However , a minimum adherence to 6 of 7 doses/week ( 85 % ) was required to protect lower female genital tract tissue from HIV , while adherence to 2 of 7 doses/week ( 28 % ) was required to protect colorectal tissue . CONCLUSIONS This model is predictive of recent PrEP trial results in which 2 - 3 doses/week was 75%-90 % effective in men but ineffective in women . These data provide a novel approach for future PrEP investigations that can optimize clinical trial dosing strategies Based on qualitative research undertaken during a phase-three microbicide gel trial , this paper explores female participants ' experiences and perceptions of gel and condom use and the opinions of their male partners and community members . Participants were aware that condoms were effective in preventing HIV infection and that the efficacy of the microbicide was unproven . Yet , in narratives about gel and condom use , participants ascribed improvements to their reproductive health and intimate relationships with men to gel use . In contrast , condoms were believed to prevent disease , yet also embodied mistrust , were believed to contain dangerous substances and were felt to block the womb . These apparently contradictory views about condoms and gels are explored in the light of conceptions of flow and blockage . Health is achieved by maintaining a steady balance of substances within the body , while preventing fluid flow results in illness . We argue that women enrolled in the trial broadened the meaning of the gel beyond its primary intended effect of preventing HIV . Through their accounts of gel use , women ‘ reinvented ’ the gel as a substance that transformed their bodies and sexual relations . This has implication s for underst and ing how local knowledge of health and illness intersects with biomedical knowledge Abstract Microbicides are a class of substances under development that could reduce the sexual transmission of HIV and other sexually transmitted diseases when applied locally to genital mucosal surfaces . Microbicide acceptability research has largely focused on product characteristics , rather than processes of negotiation within relationships about use . Gender relations , decision-making power and communication within sexual relationships are recognised as important determinants of condom and contraceptive use , and are likely to determine microbicide use also . As part of social science research linked to the Microbicides Development Programme ( MDP ) we combine relationship-based theories with anthropological work conducted with women and men using a placebo gel .  We explore communication and decision-making in gel and condom use , including constructions of risk and trust . During the MDP301 Phase III pilot study , in-depth interviews were conducted at sites in South Africa , Tanzania , Ug and a and Zambia . Following four weeks of placebo gel use , women and their partners were asked about gel use and acceptability , partner involvement , sexual practice s and condom use .  Data from 45 couples at five sites were analysed using a grounded theory approach in NVivo . Participation in the study did not require women to inform their partners , yet our data shows women seeking permission from their partners , negotiating disclosure , exchanging information and persuading or motivating for gel use . Although gel was supposedly ‘ woman-controlled ’ , men exercised considerable influence in determining whether and how it was used . Despite this , negotiations around use were largely successful , since the gel increased sexual pleasure and provided opportunities for intimate communication and the building of trust . Decisions about condom and microbicide use are made in a dyadic context and involve a complex negotiation of risk and trust . Whilst preferences relating to product characteristics are largely individual , use itself is dependent on partnership dynamics and the broader social context in which sexual risk management occurs 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 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 this r and omised , double-blind , placebo-controlled trial , we enrolled volunteers from 17 drug-treatment clinics in Bangkok , Thail and . Participants were eligible if they were aged 20 - 60 years , were HIV-negative , and reported injecting drugs during the previous year . We r and omly assigned participants ( 1:1 ; blocks of four ) to either tenofovir or placebo using a computer-generated r and omisation sequence . Participants chose either daily directly observed treatment or monthly visits and could switch at monthly visits . Participants received monthly HIV testing and individualised risk-reduction and adherence counselling , blood safety assessment s every 3 months , and were offered condoms and methadone treatment . The primary efficacy endpoint was HIV infection , analysed by modified intention-to-treat analysis . This trial is registered with Clinical Trials.gov , number NCT00119106 . FINDINGS Between June 9 , 2005 , and July 22 , 2010 , we enrolled 2413 participants , assigning 1204 to tenofovir and 1209 to placebo .  Two participants had HIV at enrolment and 50 became infected during follow-up : 17 in the tenofovir group ( an incidence of 0·35 per 100 person-years ) and 33 in the placebo group ( 0·68 per 100 person-years ) , indicating a 48·9 % reduction in HIV incidence ( 95 % CI 9·6 - 72·2 ; p=0·01 ) . The occurrence of serious adverse events was much the same between the two groups ( p=0·35 ) . Nausea was more common in participants in the tenofovir group than in the placebo group ( p=0·002 ) . INTERPRETATION In this study , daily oral tenofovir reduced the risk of HIV infection in people who inject drugs . Pre-exposure prophylaxis with tenofovir can now be considered for use as part of an HIV prevention package for people who inject drugs . FUNDING US Centers for Disease Control and Prevention and the Bangkok Metropolitan Administration 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 
    Output:
    
Relationships and trust were seen to be as or more important for product use as efficacy .
These constructs reveal an inherent inter-relationality where decision making around HIV prevention uptake and use can not be binary or mono-faceted , but rather conducted on multiple levels .