FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2976283532> ?p ?o ?g. }

• W2976283532 abstract "The guidelines are aimed at clinical professionals directly involved in, and responsible for, HIV prevention, and at community advocates and organisations responsible for supporting HIV prevention strategies in those at risk of HIV acquisition. A detailed review of the evidence base is included in Section 4. Sections 5–7 are intended to offer practical guidance in risk assessment, starting PrEP, ongoing management while on PrEP and stopping PrEP. We recognise the importance of these guidelines being inclusive and relevant to all, regardless of sexuality or gender identity or expression. For the sake of brevity in the main text of the guidelines, phrases such as “men who have sex with men” refer to cis-gender or non-binary or gender-queer men who have sex with men and “heterosexual men and women” refer to cis-gender or non-binary or gender-queer men and women who have heterosexual sex. Where sections are specifically relevant to trans people, we identify this using the terms trans people, trans men or trans women. The multidisciplinary guideline writing group developed the guidelines based on the process outlined in the BHIVA Guidelines Development Manual 1. All members of the group underwent GRADE training. We undertook a comprehensive literature review on PrEP and HIV prevention using the PICO question shown below. The recommendations are the result of a series of face-to-face and virtual meetings of the writing group and a meeting of community activists and organisations who commented on a draft of the guidelines in May 2017. The writing group also reviewed and incorporated input from the public consultation process. The literature review search was from January 2004 to May 2016. Medline, Embase and Cochrane databases were searched. Only papers in English were included and animal studies were excluded. In addition, although the formal literature review was not repeated, subsequent evidence published between May 2016 and July 2017 that the writing group felt was relevant has been included. A Grade 1 recommendation is a strong recommendation to do (or not do) something, where benefits clearly outweigh risks (or vice versa) for most, if not all, patients. Most clinicians and patients would want to follow a strong recommendation unless there is a clear rationale for an alternative approach. A strong recommendation usually starts with the standard wording “We recommend”. A Grade 2 recommendation is a weaker or conditional recommendation, where the risks and benefits are more closely balanced or are more uncertain. Alternative approaches or strategies may be reasonable depending on the individual patient's circumstances, preferences and values. A weaker or conditional recommendation usually starts with the standard wording “We suggest”. The strength of a recommendation is determined not only by the quality of evidence for defined outcomes, but also the balance between desirable and undesirable effects of a treatment or intervention, differences in values and preferences, and where appropriate, resource use. Each recommendation concerns a defined target population and is actionable. In addition to graded recommendations, the writing group has also included good practice points (GPPs). GPPs are recommendations based on the clinical judgement and experience of the working group and feedback from community and public consultation. GPPs emphasise an area of important clinical practice for which there is not, nor is there likely to be, any significant research evidence. They address an aspect of treatment and care that is regarded as such sound clinical practice that healthcare professionals are unlikely to question it, and where the alternative recommendation is deemed unacceptable. It must be emphasised that GPPs are not an alternative to evidence-based recommendations. The guideline writing group included representation from Terrence Higgins Trust and NAZ. In order to widen the stakeholder involvement, a meeting of community activists and organisations was held in May 2017, when feedback was sought on the content of the draft guidelines and recommendations prior to wider public consultation. We acknowledge the following for their helpful contributions: Yusef Azad (NAT), Takudzwa Mukiwa (THT), Will Nutland (Prepster), Greg Owen (I Want PrEP Now), Michelle Ross (CliniQ), Sophie Strachan (Sophia Forum), Marc Thompson (Prepster/Black Out UK) and George Valiotis (HIV Scotland). The guideline writing group recognises that although the PrEP trials used tenofovir disoproxil fumarate (TDF), increasingly other salts of tenofovir disoproxil (including maleate, succinate and phosphate) will be used in generic formulations. We have therefore used the acronym TDF-FTC where Truvada was used in a trial and TD-FTC to denote all other (generic) forms of tenofovir disoproxil and emtricitabine. The iPrEx study 1 was a Phase 3, randomised, double blind, placebo-controlled, multi-centre trial conducted among 2499 MSM and trans male-to-female adults (n = 339) in Peru, Ecuador, Brazil, Thailand, South Africa and the United States. Participants were randomly assigned to either a daily dose of TDF-FTC (1251 participants) or placebo (1248 participants). Primary outcome was HIV infection with a total of 3324 person-years of follow-up. Over the course of the study, 100 participants became infected with HIV; 36 in the TDF-FTC group and 64 in the placebo group, representing a 44% (95% confidence interval [CI] 15–63) reduction in HIV incidence using a modified intention-to-treat (ITT) analysis, excluding those confirmed HIV positive at randomisation. Efficacy was higher in the per-protocol analysis; at visits where adherence was >50% by self-report and pill count/dispensing, efficacy was 50% (95% CI 18–70). The PROUD study was a Phase 3, randomised, open-label, multi-centre trial conducted in 544 MSM at 13 sexual health clinics in England 2. Participants were randomly assigned to a daily dose of TDF-FTC immediately (275 participants), or after a deferral period of 12 months (269 participants). Primary outcomes were time to accrual of 500 participants and retention at 12 and 24 months; HIV infection was a secondary outcome. At interim review, the DSMB recommended that all study participants should be offered study drug. A total of 23 participants became infected with HIV over the course of the study: three in the daily TDF-FTC group and 20 in the deferred (no-PrEP) group, representing a rate difference in HIV infection of 7.8 per 100 person-years (90% CI 4.3–11.3) The relative risk reduction was 86% (90% CI 64–96%) and the number needed to treat over 1 year to prevent one HIV infection was 13 (90% CI 9–23). The IPERGAY study was a Phase 3 double-blind, randomised, multi-centre trial conducted among 414 MSM in France and Canada 3. Participants were randomly assigned to either receiving an on-demand regimen of TDF-FTC (206 participants) or placebo (206 participants). The on-demand regimen involved taking a double dose of TDF-FTC 2–24 h before sex, and a daily dose during periods of sexual risk and for 48 h (two doses) after ceasing sexual risk. Participants were followed up every 8 weeks for HIV testing and risk-reduction advice, and every 6 months for sexually transmitted infection (STI) testing for a total of 431 person-years of follow-up. Primary endpoint was HIV infection. At interim review, the placebo group was discontinued and all study participants were offered study drug. Over the course of the study, 16 people became infected with HIV: two in the TDF-FTC group and 14 in the placebo group, representing a relative risk reduction of 86% (95% CI 40–98%) in the ITT analysis. One Phase 2 safety trial, the CDC MSM Safety Trial 4, compared tenofovir (TDF) to placebo in a randomised, double-blind, placebo-controlled, wait-listed design among 400 HIV-negative MSM. Participants were randomly assigned in a 1:1:1:1 design to receive TDF or placebo immediately or after 9 months. Main endpoints were safety and behavioural outcomes. There were no infections among those taking active drug. Seven participants seroconverted: four in the placebo arm and three among delayed-arm participants who were not on the study drug. An eighth participant was HIV positive at enrolment. Two further smaller studies include a pilot feasibility and acceptability study, Project PrEPare, which recruited 58 young MSM aged 18–22 years in the United States. Participants were randomly allocated to receive a behavioural intervention alone, the behavioural intervention and PrEP (TDF-FTC) or the behavioural intervention and placebo. There were no seroconversions among the 58 participants 5. The IAVI Kenya Study was a small safety and adherence study conducted among Kenyan MSM and female commercial sex workers (CSWs). Sixty-seven MSM and five female CSWs were randomly assigned to daily TDF-FTC or placebo, or intermittent (Monday, Friday and within 2 h after sex) TDF-FTC or placebo in a 2:1:2:1 ratio. There was one seroconversion in the placebo arm 6. The iPrEx Open-label Extension (iPrEx-OLE) 7 enrolled 1603 HIV-negative men and 339 (14%) trans women who have sex with men who were previously part of PrEP studies (iPrEx, ATN082/Project PrEPare and CDC MSM Safety Trial). Participants were offered daily TDF-FTC and were followed up for 72 weeks after enrolment. Uptake was high at 76%, and this was higher among those reporting condomless receptive anal intercourse and those who were herpes simplex-2 virus (HSV-2) seropositive, suggesting use during periods of risk. HIV incidence was 1.8 infections per 100 person-years, compared with 2.6 infections per 100 person-years in those who concurrently did not choose PrEP (hazard ratio [HR] 0.51, 95% CI 0.26–1.01, adjusted for sexual behaviours) 7. Examination of drug levels by dried blood spot testing was extrapolated to pill taking and compared to HIV incidence each quarter. No seroconversions were seen when drug levels were compatible with taking four or more pills per week. The IPERGAY Open-label Extension (IPERGAY-OLE) enrolled 362 individuals to take on-demand TDF-FTC and followed them for a median of 11.7 months, of whom 299 (83%) completed follow-up with a single HIV infection (0.19 per 100 person-years, 95% CI 0.01–1.08) 8. A community-based clinic in San Francisco screened 1249 MSM (and three trans men) and offered PrEP with TDF-FTC with 95.5% uptake. Condomless sex was reported by 93% at enrolment. After a maximum of 16 months’ follow-up there were no new HIV infections in the men enrolled in the programme 9. At the time of writing there have been three case reports of HIV transmissions in MSM taking PrEP despite apparent confirmed adherence. Two individuals were infected with resistant virus and, in one case, transmission occurred with wild-type virus sensitive to both tenofovir and emtricitabine 10. Efficacy of PrEP is highly dependent on adherence, with a meta-analysis of PrEP studies 12 demonstrating that adherence is a significant moderator of PrEP effectiveness. The higher the levels of adherence to oral PrEP in the study population, as measured by detectable drug, the greater the efficacy. In the iPrEX study, adherence was monitored using pill count and self-reported adherence. Pharmacokinetic plasma and intracellular drug-level sampling was conducted in a pre-specified subgroup analysis where subjects with HIV infection were matched with two controls selected from seronegative subjects. In those who had detectable drug levels of TDF-FTC, the reduction in HIV incidence was 92% (95% CI 40–99%) compared to those who had no drug detected 1, suggesting that a high level of adherence is associated with a high level of efficacy. In the PROUD study, adherence was monitored using prescription data, self-reported adherence and drug levels in a convenience sample of study participants. Overall, sufficient study drug was prescribed for 88% of the total follow-up time and tenofovir was detected in all samples taken from 52 participants who reported taking study drug within the preceding 3 days 2. In the IPERGAY study, adherence was monitored using pill counts, self-reported adherence and drug levels in a subset of 113 participants. Of participants in the active treatment group who had drug levels measured, protective drug levels of tenofovir were detected in 86%. However, computer-assisted interview (CASI) data collected in 319 participants in the randomised phase suggested that only 43% of people took study drug correctly during last sexual intercourse, 29% took a suboptimal dose and 28% did not take the study drug at all 3. In the open-label phase, adherence in 362 men completing 1617 CASI returns reported 50% of men taking study drug correctly during last sexual encounter, 24% taking a suboptimal dose and 26% taking no study drug at all 8. Comparison of adherence to different regimens of TDF-FTC PrEP has been investigated in MSM in the HPTN 067 (ADAPT) study. The study recruited MSM and trans women in Harlem (New York, USA) and Thailand and heterosexual women in South Africa. Following a 4-week phase of daily dosing, participants were randomly assigned 1:1:1 to one of three regimens: daily dosing (“daily”) or one tablet twice a week and one tablet post sex (“time driven”) or one tablet 24–48 h before sex and one tablet within 2 h after sex (“event-based”). Results from 178 Thai MSM showed that coverage (defined as taking more than one pill in the 4 days before sex and more than one pill in the 24 h afterwards) was significantly higher in the daily (85% of events covered) and time-driven (84%) arms than in the event-driven arm (74%). Two seroconversions occurred in the 4 week pre-randomisation phase 13. In 179 MSM in Harlem, figures were 66%, 47% and 52%, respectively, with one seroconversion in the pre-randomisation phase and one in the randomised phase 14. Adherence was higher in the daily-dose arms: in Thailand, 85% of daily doses, 79% of twice-weekly doses, and 65% of event-driven doses were taken as prescribed. In Harlem, the respective figures were 65%, 46% and 41%. Although these represent two diverse populations of MSM in different settings, the study demonstrated similar coverage of sex acts for daily and non-daily regimens with both groups demonstrating lower adherence and coverage rates for the event-driven approach. Higher coverage of events in the Thai MSM was associated with older age and higher level of education. Use of stimulant drugs and higher sexual frequency was associated with lower coverage 15. To date, studies of TDF-FTC PrEP suggest short-term safety. A meta-analysis of PrEP studies 12 demonstrated no difference in the proportions of adverse events comparing PrEP to placebo across 10 placebo-controlled RCTs (odds ratio [OR] 1.01, 95% CI 0.99–1.03, P = 0.27) with no differences seen in subgroup analysis that included mode of acquisition, adherence, sex, drug regimen, dosing or age. No differences were seen in grade 3 or 4 adverse events comparing PrEP and placebo groups across 11 placebo-controlled RCTs (risk ratio [RR] 1.02, 95% CI 0.92–1.13, P = 0.76). Results were not presented by subgroup. In the iPrEx study, there was no difference in reported adverse events between the two study arms: 867/1251 (67%) of participants in the TDF-FTC arm reported any adverse event, compared to 877/1248 (70%) in the control arm. Both arms reported similar rates of grade 3 and 4 adverse events: 151/1251 (12%) of TDF-FTC participants compared to 164/1248 (13%) of control-arm participants 1. There was no difference in permanent or temporary discontinuation of study drug between the two arms: 25/1251 (2%) permanent discontinuations in the intervention arm compared to 27/1248 (2%) in the placebo arm and a total of 79/1251 (6%) permanent or temporary discontinuations in the intervention arm compared to 72/1248 (6%) in the placebo arm. However, nausea was more common among those taking TDF-FTC compared to placebo in the first month (95% vs. 5%). Depression-related adverse events were the most common severe or life-threatening adverse events reported in iPrEx, but were not associated with being randomly assigned to TDF-FTC (OR 0.66, 95% CI 0.35–1.25) 16. In the PROUD study, 21/275 participants (8%) interrupted or missed study drug doses because of adverse events, the commonest of which were headache and nausea 2. In IPERGAY, drug-related gastrointestinal adverse events were reported more commonly in the TDF-FTC group compared to the placebo group (14% vs. 5%, P = 0.002), but there was no difference in the frequency of grade 3 or 4 adverse events 3. PrEP trials have shown modest, but statistically significant declines in renal function with administration of daily TDF-FTC, but the incidence of serious renal events was very low and mostly reversible. In PROUD, three participants interrupted drug due to elevated creatinine concentrations (two were classed as mild elevation, defined as 1.1–1.3 times the upper limit of normal [ULN], and one as moderate, 1.4–1.8 ULN), although the most likely explanation in one man was recreational drug use and the other two men were older with comorbidities 2. In the IPERGAY study, 18% of active drug participants experienced elevated creatinine levels compared to 10% of placebo group (P = 0.03). All, but one were mild and transient and none led to discontinuation of study drug 3. In the iPrEx study, use of TDF-FTC was associated with a mild non-progressive decrease in estimated creatinine clearance (CrCl) of 2.4% from baseline, which was reversible 14. Creatinine elevations of >1.1 ULN were similar between active and placebo arms, occurring in 32 (2.6%) in the active arm and 24 (2.2%) in the placebo arm (RR 1.35, 95% CI 0.80–2.3). Most excess creatinine elevations in the active arm of the study (median follow-up 72 weeks) occurred at 12–24 weeks and all occurred at <48 weeks. Proteinuria by dipstick was detected regularly (613/5081 [12%] dipsticks performed), but there was no between-group difference in the proportion of participants ever positive for proteinuria (20% placebo vs. 21% TDF-FTC; P = 0.62). In addition, the positive predictive value of proteinuria in predicting a confirmed creatinine elevation was poor at 0.7% 14. In iPrEx-OLE the probability of CrCl falling to ≤60 mL/min at least once over the first year on PrEP was low, but was more likely when participants started PrEP at older ages (>40 years) or with a starting CrCl ≤90 mL/min 15. For participants under 40 years of age, the mean decline in CrCl over the duration of the study (median 72 weeks) was modest (−2.6%) and no patients experienced a CrCl drop to ≤60 mL/min, even in those with full adherence to daily dosing, indicating that annual monitoring of renal function in this group should be sufficient. However, being aged >40 years or with a lower baseline creatinine clearance (≤90 mL/min) at initiation of PrEP were independently associated with a risk of CrCl falling to ≤60 mL/min, especially with daily dosing. This suggests that more frequent renal monitoring on PrEP may be required in older PrEP users (>40 years) and in those with marginal renal function at baseline, even if there are no other concomitant risk factors for renal disease. In an iPrEx sub-study of 500 participants who underwent 6-monthly DEXA scans to assess bone mineral density (BMD), a small net decrease in BMD of 0.7–1% was seen among those randomly assigned to TDF-FTC (n = 247) compared to placebo (n = 256) after 24 weeks in both spine and total hip measures 17. There are no long-term data on bone health for people on TDF-FTC PrEP. In the CDC MSM study, in multivariate analysis, back pain was associated with use of TDF and also a small decrease in BMD among a subset of 184 men in the San Francisco site. However, TDF use was not associated with bone fractures 18. In the iPrEx trial, FTC-related drug resistance developed in two participants who had unrecognised acute HIV infection at baseline 19. These individuals had a negative antibody test before starting PrEP, but later tested positive. In the PROUD study, two of the three participants with a positive HIV test at enrolment or the 4-week visit had FTC-related drug resistance; no resistance was detected in participants who acquired HIV post-randomisation 2. In IPERGAY, none of the incident HIV infections post-randomisation demonstrated resistance mutations to study drug 3. In a meta-analysis, Fonner et al. reviewed results from six trials that reported cases of FTC or TDF drug resistance using standardised genotypic laboratory assays 12. Although the only study of MSM included in this analysis was iPrEx, the risk factors associated with development of drug resistance will be similar in MSM and people who have heterosexual sex. The risk of developing an FTC-related mutation among those acutely infected with HIV at enrolment was significantly higher in the group randomly allocated to receive TDF-FTC compared to placebo (risk ratio 3.72, 95% CI 1.23–11.23, P = 0.02). The risk of a TDF-related mutation was not statistically different between PrEP and placebo, regardless of PrEP regimen, among those acutely infected at enrolment. Additionally, six (2%) TDF- or FTC-resistant infections occurred among 544 post-randomisation HIV infections: five in PrEP groups and one in a placebo group. Numbers were too small to calculate a pooled relative risk. Risk behaviour has been measured using outcomes including STI diagnoses, condom use and sexual partner numbers. The most clinically relevant outcome is STI diagnoses, not least because the other two indicators are self-reported and, as such, subject to reporting bias. In the placebo-controlled trials, one purpose of the placebo is to control for behaviour, and it is not possible to comment on the impact of PrEP on behaviour, as participants do not know if they are on active drug. However, it is possible to evaluate the impact of the risk-reduction support provided to all participants, and there were demonstrable benefits in iPrEx, the CDC MSM Safety Trial, but not the IAVI Kenya study. In the iPrEx study, both PrEP and placebo groups reported increased condom use over the course of the study and reported condom use did not differ between the arms (P = 0.36) 1. The number of reported receptive sexual intercourse partners in both arms also declined over the course of the study, with no significant difference in the number of partners reported in each group at each time point (P = 0.97) 1. The reduction in risk behaviours may reflect the fact that the majority of iPrEx participants came from populations with little access to risk-reduction support. In IPERGAY, there were no significant differences between TDF-FTC and placebo groups in the proportion of condomless receptive anal sex (P = 0.40) and incident STIs (P = 0.10). There was a slight but significant decrease in the number of sexual partners in the previous 2 months in the placebo group compared to the TDF-FTC group (7.5 vs. 8, P = 0.001) 3, 20. In the CDC MSM Safety Trial (also placebo-controlled), mean number of sexual partners in the previous 3 months and the proportion reporting condomless anal sex declined over 24 months of follow-up. The IAVI Kenya study, which included MSM, was the only trial to report an increase in study partners from baseline to follow-up, but partners may have been underreported at baseline 6. In the open-label PROUD study, in which participants knew they were taking PrEP and that it was at least partially effective, there was no difference between the immediate and deferred (no-PrEP) groups in the total number of sexual partners (P = 0.57) in the 3 months prior to the 1-year questionnaire, but a greater proportion of the immediate group reported receptive anal sex without a condom with 10 or more partners compared to the deferred group (21% vs. 12%, P = 0.03). There was no difference in the frequency of bacterial STIs during the randomised phase (P = 0.74) 2. In the iPrEx-OLE study, both groups reported decreases in reported condomless receptive anal intercourse from 34% (377/1115) to 25% (232/926 P = 0.006) among those accepting PrEP and from 27% (101/369) to 20% (61/304; P = 0.03) in the group who declined PrEP. Conversely, in IPERGAY-OLE there was a much higher baseline rate and a significant increase in reported condomless sex at last receptive anal intercourse from 77% at baseline to 86% at 18 months (P = 0.003 for trend) 8. Examination of three different trajectories of condom use (low, medium and high) and four of PrEP use over time in IPERGAY-OLE shows that in the majority of men, declines in condom use were compensated by increased on-demand PrEP use, but in a minority of men this was not the case. Compensation by using on-demand PrEP was lower in younger men for all three condom trajectories 21. In a large observational cohort study of MSM PrEP in a community-based clinic in San Francisco, self-reported condom use for different sub-cohorts of men taking PrEP for periods of 1–16 months was unchanged in 38–61%, increased in 5–12% and reduced in 16–48% 9. Both the PROUD and IPERGAY studies documented high levels of bacterial STIs in MSM throughout the course of follow-up. Within IPERGAY, participants were screened at enrolment and every 6 months during follow-up for chlamydia and gonorrhoea (with triple site nucleic acid amplification tests) and syphilis 10. Of participants receiving TDF-FTC, 41% acquired a new STI during follow-up, compared to 33% in the placebo arm; most STIs were rectal and 10% acquired a new syphilis infection 3. Similar results were observed within the PROUD study where 3- to 6-monthly STI screening was offered and the proportions with a bacterial STI were 50% and 57% of men diagnosed with an STI, respectively, in the deferred and immediate treatment arms of the study (P = 0.74). Similarly to IPERGAY, 10% of individuals in PROUD acquired a new syphilis infection 2. In iPrEx OLE the incidence of syphilis was similar in both groups, although numerically higher among PrEP users (7.2/100 person-years compared to 5.4/100 person-years in non-PrEP users, HR 1.35, 95% CI 0.83–2.19). In IPERGAY, incidence rate of first STI was 35.2 per 100 person-years in the double-blind phase, and 40.6 per 100 person-years in the open-label phase 3. Incident hepatitis C has also been reported in clinical trials and PrEP access projects. In Amsterdam, HIV-negative MSM who enrolled in the Amsterdam PrEP demonstration project had considerably higher hepatitis C virus (HCV) prevalence at 4.8% than HIV-negative MSM in the general Amsterdam STI clinic survey at 0.3–1.2% 22. Genetic analyses suggested that circulating HCV strains in HIV-negative men starting PrEP were similar to those in local HIV/HCV co-infected MSM. In the PROUD study, 5/160 (3.1%) participants who had tested on one or more occasions for HCV had incident HCV infection (3.1%). There were three incident HCV infections in the immediate arm and two in the deferred arm 2. In IPERGAY, overall, there were five incident HCV infections 3 suggesting that HIV-negative men on PrEP are at risk of HCV infection and should undergo regular testing for HCV while on PrEP. Two RCTs have demonstrated the efficacy of daily oral PrEP in preventing HIV acquisition among heterosexual individuals. One Phase 3 RCT, Partners PrEP 1, assessed the efficacy of daily oral TDF vs. TDF-FTC vs. placebo in serodifferent heterosexual couples in East Africa and one Phase 3 RCT, TDF-2 2, evaluated TDF-FTC vs. placebo in sexually active heterosexual adults at high risk of HIV acquisition in Botswana. No studies have evaluated the efficacy of an on-demand PrEP regimen in heterosexuals and to date there have been no RCTs undertaken in heterosexual men and women in high-income countries. Although there is no reason to think the biological efficacy would be different, given the lack of RCTs in heterosexuals in high-income countries, it remains difficult to generalise the finding of high PrEP efficacy from these two trials in sub-Saharan Africa (SSA) to the UK because HIV incidence is much lower, and no well-defined group of heterosexuals with high HIV incidence can be identified in national surveillance data. Furthermore, there are likely to be differences in cultural beliefs and sociodemographic circumstances that influence adherence and efficacy and further complicate any extrapolation of the data. Two RCTs (FEM-PrEP 3 and VOICE 4), both in heterosexual women in SSA, reported low efficacy rates of daily oral PrEP. In both cases, the studies were well conducted and the null results, and inconsistency of the results when compared to TDF-2 and Partners PrEP, are primarily attributed to low adherence (measured using drug levels) to the study drug in the intervention arm. Partners PREP was a double-blind, placebo-controlled Phase 3 RCT following 4747 heterosexual couples, comparing single and dual agent PrEP (TDF vs. TDF-FTC) with placebo conducted from 2008 to 2010 1. Participants were sexually active serodifferent heterosexual couples in Uganda and Kenya. HIV-negative participants were aged between 18 and 65 years, sexually active with an HIV-positive partner (≥6 episodes of vaginal intercourse with HIV-positive partner in the past 3 months) with no chronic HBV infection. HIV-negative women who were breastfeeding, pregnant or planning to become pregnant were excluded from the study. The study also excluded HIV-negative participants with glycosuria or proteinuria, ongoing therapy with certain drugs, and a history of pathological bone fractures not related to trauma. HIV-positive sexual partners were >18 years old, sexually active, with CD4 cell counts ≥250 cells/mL, no history of AIDS-defining illnesses and not using antiretrovirals (ARVs). The HIV incidence in the control arm was 1.99 per 100 person-years. Overall, the study found the efficacy of PrEP using TDF alone was 67% (95" @default.
• W2976283532 created "2019-10-03" @default.
• W2976283532 creator A5006973430 @default.
• W2976283532 creator A5008829549 @default.
• W2976283532 creator A5016653600 @default.
• W2976283532 creator A5016768242 @default.
• W2976283532 creator A5021038080 @default.
• W2976283532 creator A5028363701 @default.
• W2976283532 creator A5033938755 @default.
• W2976283532 creator A5041136521 @default.
• W2976283532 creator A5046254202 @default.
• W2976283532 creator A5051652315 @default.
• W2976283532 creator A5053823377 @default.
• W2976283532 creator A5059133452 @default.
• W2976283532 creator A5061610668 @default.
• W2976283532 creator A5077677785 @default.
• W2976283532 creator A5081186229 @default.
• W2976283532 creator A5081402869 @default.
• W2976283532 date "2019-03-01" @default.
• W2976283532 modified "2023-10-11" @default.
• W2976283532 title "BHIVA/BASHH guidelines on the use of HIV pre–exposure prophylaxis (PrEP) 2018" @default.
• W2976283532 cites W1413161224 @default.
• W2976283532 cites W1552487149 @default.
• W2976283532 cites W1554940778 @default.
• W2976283532 cites W1723966030 @default.
• W2976283532 cites W1895220657 @default.
• W2976283532 cites W1904680373 @default.
• W2976283532 cites W1964489937 @default.
• W2976283532 cites W1971644621 @default.
• W2976283532 cites W1974380624 @default.
• W2976283532 cites W1981177608 @default.
• W2976283532 cites W1981376003 @default.
• W2976283532 cites W1982336966 @default.
• W2976283532 cites W1987384148 @default.
• W2976283532 cites W1988338542 @default.
• W2976283532 cites W1989906690 @default.
• W2976283532 cites W1999170818 @default.
• W2976283532 cites W1999419079 @default.
• W2976283532 cites W2000761749 @default.
• W2976283532 cites W2008815987 @default.
• W2976283532 cites W2010783491 @default.
• W2976283532 cites W2017605567 @default.
• W2976283532 cites W2021803277 @default.
• W2976283532 cites W2022226876 @default.
• W2976283532 cites W2032231409 @default.
• W2976283532 cites W2037850311 @default.
• W2976283532 cites W2038662816 @default.
• W2976283532 cites W2040595978 @default.
• W2976283532 cites W2044369525 @default.
• W2976283532 cites W2047690132 @default.
• W2976283532 cites W2051929758 @default.
• W2976283532 cites W2053676070 @default.
• W2976283532 cites W2060132628 @default.
• W2976283532 cites W2063311086 @default.
• W2976283532 cites W2068158763 @default.
• W2976283532 cites W2071747121 @default.
• W2976283532 cites W2073370688 @default.
• W2976283532 cites W2073986430 @default.
• W2976283532 cites W2075290265 @default.
• W2976283532 cites W2088232432 @default.
• W2976283532 cites W2098793704 @default.
• W2976283532 cites W2101221094 @default.
• W2976283532 cites W2103920597 @default.
• W2976283532 cites W2106471405 @default.
• W2976283532 cites W2108393429 @default.
• W2976283532 cites W2110530964 @default.
• W2976283532 cites W2115046127 @default.
• W2976283532 cites W2116531236 @default.
• W2976283532 cites W2116728300 @default.
• W2976283532 cites W2117057469 @default.
• W2976283532 cites W2119989719 @default.
• W2976283532 cites W2120022902 @default.
• W2976283532 cites W2120083758 @default.
• W2976283532 cites W2120382102 @default.
• W2976283532 cites W2120675005 @default.
• W2976283532 cites W2132977017 @default.
• W2976283532 cites W2136985213 @default.
• W2976283532 cites W2139796029 @default.
• W2976283532 cites W2142748692 @default.
• W2976283532 cites W2144000274 @default.
• W2976283532 cites W2145754461 @default.
• W2976283532 cites W2147889744 @default.
• W2976283532 cites W2150644408 @default.
• W2976283532 cites W2152505869 @default.
• W2976283532 cites W2154854455 @default.
• W2976283532 cites W2162226934 @default.
• W2976283532 cites W2168251450 @default.
• W2976283532 cites W2171058769 @default.
• W2976283532 cites W2171609071 @default.
• W2976283532 cites W2173274566 @default.
• W2976283532 cites W2174951518 @default.
• W2976283532 cites W2181563210 @default.
• W2976283532 cites W2183205588 @default.
• W2976283532 cites W2275495519 @default.
• W2976283532 cites W2278817684 @default.
• W2976283532 cites W2281762096 @default.
• W2976283532 cites W2290010664 @default.
• W2976283532 cites W2303386886 @default.
• W2976283532 cites W2303615074 @default.
• W2976283532 cites W2313654022 @default.

• next