Appropriate usage of post-exposure prophylaxis-in-pocket for HIV prevention by individuals with low-frequency exposures.

PEP-In-Pocket (Post-Exposure Prophylaxis-In-Pocket, or "PIP") is a biobehavioural HIV prevention strategy wherein patients are proactively identified and given a prescription for HIV post-exposure prophylaxis (PEP) medications to self-initiate in case of high-risk exposures. We evaluated this strategy in a prospective observational study at two hospital-based clinics in Toronto, Canada. HIV-negative adults using PIP underwent chart review and completed quarterly electronic questionnaires over 12 months. The primary objective was to quantify appropriate PIP initiation, defined as starting PIP within 72 h of a high-risk exposure. Secondary objectives were to quantify HIV seroconversions, changes in sexual risk behaviour, sexual satisfaction, and satisfaction with the PIP strategy. From 11/2017 to 02/2020, 43 participants enrolled and completed ≥1 questionnaire. PIP was self-initiated on 27 occasions by 15 participants, of which 24 uses (89%) were appropriate, 2 were unnecessary, and 1 was for an unknown exposure. Chart review identified no inappropriate non-use. Over 32 person-years of testing follow-up, we observed zero HIV seroconversions. Sexual risk declined modestly over follow-up, with a HIRI-MSM (HIV Incidence Risk Index for MSM) change of -0.39 (95% CI = -0.58, -0.21 per 3 months, p < .001). Sexual satisfaction was stable over time. At 12 months, 31 (72%) remained on PIP, 8 (19%) had transitioned to pre-exposure prophylaxis and 4 (9%) were lost-to-follow-up. Among participants who remained on PIP and completed questionnaires at 12 months, 24/25 (96%) strongly/somewhat agreed that PIP decreased their anxiety about contracting HIV and 25/25 (100%) strongly/somewhat agreed that they would recommend PIP to a friend. PIP is a feasible HIV prevention strategy in carefully selected individuals at modest HIV risk.

Community and Health Care Provider Preferences for Bacterial Sexually Transmitted Infection Testing Interventions for Gay, Bisexual, and Other Men Who Have Sex With Men: e-Delphi Study.

BACKGROUND: Canadian clinical guidelines recommend at least annual and up to quarterly bacterial sexually transmitted infection (STI) testing among sexually active gay, bisexual, and other men who have sex with men (GBM). However, testing rates are suboptimal. Innovative solutions are needed to close the gap because there is currently limited knowledge on how best to approach this issue. OBJECTIVE: Our aim was to build consensus regarding interventions with the greatest potential for improving local STI testing services for GBM communities in Toronto, Ontario, Canada, using a web-based e-Delphi process. METHODS: The e-Delphi method involves using a panel format to conduct successive rounds of prioritization, with feedback between rounds, to determine priorities among groups. We recruited experts separately from the community (GBM who sought or underwent STI testing in the preceding 18 months; conducted between October 2019 and November 2019) and health care providers (those who offered STI testing to GBM in the past 12 months; conducted between February 2020 and May 2020). The experts prioritized 6 to 8 potential interventions on a 7-point Likert scale ranging from definitely not a priority to definitely a priority over 3 survey rounds and ranked their top 3 interventions. Consensus was defined as ≥60% within a ±1 response point. Summaries of responses were provided in successive rounds. We reported the percentage of a priority (encompassing somewhat a priority, a priority, and definitely a priority responses) at the end of the final round of the survey. RESULTS: Of the community experts (CEs), 84% (43/51) completed all rounds; 19% (8/43) were living with HIV; 37% (16/43) were HIV negative and on pre-exposure prophylaxis; and 42% (18/43) were HIV negative and not on pre-exposure prophylaxis. We reached consensus on 6 interventions: client reminders (41/43, 95%), express testing (38/43, 88%), routine testing (36/43, 84%), an online booking app (36/43, 84%), online-based testing (33/43, 77%), and nurse-led testing (31/43, 72%). The CEs favored convenient interventions that also maintain a relationship with their provider. Of the provider experts (PEs), 77% (37/48) completed all rounds; 59% (22/37) were physicians. Consensus was reached on the same 6 interventions (range 25/37, 68%, to 39/39, 100%) but not for provider alerts (7/37, 19%) and provider audit and feedback (6/37, 16%). Express testing, online-based testing, and nurse-led testing were prioritized by >95% (>37/39) of the PEs by the end of round 2 because of streamlined processes and decreased need to see a provider. CONCLUSIONS: Both panels were enthusiastic about innovations that make STI testing more efficient, with express testing rating highly in both the prioritizations and top 3 rankings. However, CEs preferred convenient interventions that involved their provider, whereas PEs favored interventions that prioritized patient independence and reduced patient-provider time. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/13801.

Sexual health promotion for sexual and gender minorities in primary care: a scoping review protocol.

INTRODUCTION: Sexual and gender minorities (SGMs) face health disparities related to systemic discrimination and barriers to sexual health. Sexual health promotion encompasses strategies that enable individuals, groups and communities to make informed decisions regarding their sexual well-being. Our objective is to describe the existing sexual health promotion interventions tailored for SGMs within the primary care context. METHODS AND ANALYSIS: We will conduct a scoping review and search for articles in 12 medical and social science academic databases on interventions that are targeted towards SGMs in the primary care context in industrialised countries. Searches were conducted on 7 July 2020 and 31 May 2022. We defined sexual health interventions in the inclusion framework as: (1) promote positive sexual health, or sex and relationship education; (2) reduce the incidence of sexually transmitted infections; (3) reduce unintended pregnancies; or (4) change prejudice, stigma and discrimination around sexual health, or increase awareness surrounding positive sex. Two independent reviewers will select articles meeting inclusion criteria and extract data. Participant and study characteristics will be summarised using frequencies and proportions. Our primary analysis will include a descriptive summary of key interventional themes from content and thematic analysis. Gender-based Analysis Plus will be used to stratify themes based on gender, race, sexuality and other identities. The secondary analysis will include the use of the Sexual and Gender Minority Disparities Research Framework to analyse the interventions from a socioecological perspective. ETHICS AND DISSEMINATION: No ethical approval is required for a scoping review. The protocol was registered on the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/X5R47). The intended audiences are primary care providers, public health, researchers and community-based organisations. Results will be communicated through peer-reviewed publication, conferences, rounds and other opportunities to reach primary care providers. Community-based engagement will occur through presentations, guest speakers, community forums and research summary handouts.

HSV-2 infection and HPV incidence, persistence, and precancerous lesions in a cohort of HPV-vaccinated women living with HIV.

BACKGROUND: Several co-factors for HPV oncogenesis have been proposed, including co-infection with HSV-2. We assessed the relationship between HSV-2 infection and HPV-related outcomes in quadrivalent HPV-vaccinated (qHPV) women living with HIV (WLWH). METHODS: In this multi-site study of immunogenicity and efficacy of the qHPV vaccine in WLWH, visits took place at months -3, 0, 2, 6, 12, 18, 24, and annually thereafter. Participants provided clinical data and cervico-vaginal swabs for HPV DNA detection; baseline serum was tested for HSV-2 type-specific antibodies. We used non-parametric statistics to compare HPV-related outcomes by HSV-2 serostatus and use of anti-HSV medication. RESULTS: 151 baseline serum samples underwent HSV-2 testing. At baseline, median age was 39 years, median CD4 count was 500 cells/mm3, and 70% had an HIV viral load of <50 copies/mL. Baseline HSV-2 seroprevalence was 76.2%. HSV-2 seropositivity was associated with increased age (p = 0.006). Controlling for age and median CD4 count, HSV-2 seropositivity was not associated with HPV incidence, persistence, and precancerous lesions. The use of anti-HSV medications was associated with higher odds of HSIL cytology (OR = 3.35, 95% CI = 1.03,11.26) and a greater number of HPV types detected (OR = 1.18, 95% CI = 1.00,1.39). Results were similar in sensitivity analyses using an index value of 3.5. The presence of HSV lesions during the study was not associated with HPV outcomes. CONCLUSIONS: HSV-2 seropositivity was common in this cohort of WLWH in Canada but was not associated with multiple measures of HPV incidence, persistence, and precancerous lesions. However, the use of anti-HSV medications was associated with HSIL cytology and number of HPV types detected.

An up-to-date evaluation of dolutegravir/abacavir/lamivudine for the treatment of HIV.

INTRODUCTION: There are more than 30 agents available for the treatment of HIV with guidelines shifting toward integrase strand transfer inhibitors (INSTIs) as part of first line therapy. The fixed dose combination of dolutegravir (DTG), abacavir (ABC), and lamivudine (3TC) is a convenient, well tolerated, and highly effective option for treating HIV infection and remains a first line therapy across several prominent guidelines. AREAS COVERED: In this drug evaluation, the authors provide a comprehensive overview of DTG/ABC/3TC for the treatment of HIV including the pharmacokinetics, pharmacodynamics, efficacy, safety, and tolerability. The authors also provide the reader with their expert perspectives on this particular treatment strategy. EXPERT OPINION: While DTG/ABC/3TC remains a valuable HIV treatment option, newer combination regimens have entered the market. Bictegravir with tenofovir alafenamide and emtricitabine offers the benefit of same day initiation and efficacy in hepatitis B co-infection, while new two-drug regimens enhance the simplicity of HIV treatment. Continued study is required into the mechanisms and optimal management strategies for weight gain for many regimens, including DTG/ABC/3TC.

Feasibility of implementing a same-day electronic screening tool for clinical assessment to measure patient-reported outcomes for eliciting actionable information on adherence to HIV medication and related factors in a busy Canadian urban HIV clinic.

BACKGROUND: An optimal adherence to antiretroviral therapy (ART) is fundamental for suppression of HIV viral load and favourable treatment outcomes. Patient-reported outcomes (PROs) are effective tools for improving patient-provider communication and focusing providers' awareness on current health problems. The objectives of this analysis were (1) to determine the feasibility of implementing an electronic screening tool to measure PROs in a Canadian HIV clinic to obtain information on ART adherence and related factors and (2) to determine the factors related to sub-optimal adherence. METHODS: This implementation research with a convenience sample of 600 people living with HIV (PLWH) was conducted in a busy, academic, urban HIV clinic in Toronto, Canada. PLWH were approached to participate in PRO assessments just prior to their in-clinic appointments, including health-related domains such as mental health, housing, nutrition, financial stress and medication adherence, and responses were summarized on a single sheet available for providers to review. Feasibility of implementing PROs was assessed by quantifying response rate, completion rate, time taken and participation rate. Medication adherence was elicited by self-report of the percentage of prescribed HIV medications taken in the last month. Unadjusted and adjusted odds ratios were estimated from logistic regression models to identify factors associated with adherence of <95%. RESULTS: Of the 748 PLWH invited to participate, 692 (participation rate: 92.5%) completed the PRO assessments as standard of care in clinic. Of these, 600 consented to the use of their PRO results for research and were included in this analysis. The average response rate to the ART-related questions was 96.8% and mean completion rate was 95.5%. The median time taken to complete the assessment was 12.0 (IQR = 8.4-17.3) min, adjusted 8.7 (IQR = 7.2-10.8) min. 445 (74.9%) of participants were male, and 153 (26.2%) reported dissatisfaction with ART. 105 (19.7%) of the PLWH reported ART adherence of <95%. Multivariable logistic regression identified the following risk factors for sub-optimal adherence: dissatisfaction with ART (OR = 2.30, 95% CI 1.38-3.83), not having a family doctor or not visiting a family doctor in last year (OR = 1.69, 95% CI 1.02-2.79). CONCLUSION: Collecting self-reported health information from PLWH through PROs in a busy urban clinic was feasible and can provide relevant information to healthcare providers on issues related to adherence. This has a potential to help in individualizing ambulatory care.

Patient perspectives on the implementation of routinised syphilis screening with HIV viral load testing: Qualitative process evaluation of the Enhanced Syphilis Screening Among HIV-positive Men trial.

BACKGROUND: Syphilis infections have been on the rise, affecting men living with HIV in urban centres disproportionately. Since individuals in HIV care undergo routine blood testing, HIV clinics provide practical opportunities to conduct regular and frequent syphilis testing. Following the implementation of a routine syphilis testing intervention in HIV outpatient clinics, we conducted a qualitative process evaluation of patient experiences to measure patient acceptability, barriers to implementation, and facilitators of successful uptake. METHODS: Upon completion of the trial, which took place at four HIV outpatient clinics in Toronto and Ottawa, Canada, we recruited male patients attending these clinics from November 2017 to April 2018. Interviews were conducted on-site and were audio-recorded and transcribed verbatim. All participants provided written informed consent. Interview data were analyzed using grounded theory, assessing qualitative modulators of effective uptake of routinised syphilis testing. RESULTS: A total of 21 male patients were interviewed. Overall, interviewees found the clinical intervention acceptable, endorsing the practice of routinising syphilis testing alongside regular viral load bloodwork. Some men preferred, based on their self-assessment of syphilis risk, to opt out of testing; we considered this as a potential barrier to uptake of population-wide routinised syphilis testing. Interviewees also identified multiple facilitators of successful uptake, including the de-stigmatising of STI testing as a consequence of the universal nature of routinised testing. Participants recommended a routinised syphilis screening intervention to give patients peace of mind surrounding their sexual health. Participants identified HIV care clinics as comfortable and efficient locations to offer testing. CONCLUSIONS: Overall, most men were in support of implementing routinised syphilis testing as part of standard HIV care. From the patient perspective, HIV care clinics are convenient places to be tested for syphilis, and the routine approach was viewed to have a de-stigmatisng effect on syphilis testing. TRIAL REGISTRATION: ClinicalTrials.gov NCT02019043; registered December 23, 2013.

Infection with antiretroviral-susceptible HIV in an individual adherent to pre-exposure prophylaxis: strategies for treatment initiation.

HIV pre-exposure prophylaxis (PrEP) is effective at preventing sexual acquisition of HIV, and failures in clinical trials are largely attributable to medication nonadherence. We report here a case of infection with a fully susceptible strain of HIV in an individual adherent to PrEP as demonstrated by pharmacy records and intracellular tenofovir diphosphate levels. At diagnosis, the viral load was 90 copies/mL precluding initial genotype testing due to low copy number. While PrEP failure is rare, this case underscores the importance of regular HIV testing for patient on PrEP and prompts discussion regarding the approach to treatment following failure where an initial genotype is not yet available or not possible due to low viral load. Few other case reports of PrEP failure exist in the literature and approaches to treatment varied widely. We suggest the initial viral copy number may guide next steps and discuss the risks and benefits of stopping PrEP, escalating therapy with integrase inhibitors or boosted protease inhibitors, or switching to non-nucleoside antiretroviral treatment regimens.

The effect of tenofovir disoproxil fumarate on bone mineral density: a systematic review and meta-analysis.

BACKGROUND: We conducted a systematic review and meta-analysis (CRD#42017070552) to quantify the impact of oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) on bone mineral density (BMD) and the risk of osteoporosis, low bone mass and fractures, among people taking it as pre-exposure prophylaxis (PrEP), HIV treatment and HBV treatment. METHODS: We searched MEDLINE and EMBASE for randomized controlled trials published from 1997-2018 reporting BMD, osteoporosis, low bone mass and/or fractures in treatment-naive patients taking compared with not taking TDF for 48 ±4 weeks. We pooled outcomes using DerSimonian random-effects models. RESULTS: Our search yielded 5,178 abstracts, representing 3,865 articles, with 25 meeting the inclusion criteria. TDF was associated with greater BMD decline when taken as PrEP (lumbar spine: mean difference [MD]=-0.82%, 95% CI=-1.28, -0.37%, I2=38%; total hip: MD=-0.81%, 95% CI=-1.22, -0.40%, I2=48%) and HIV treatment (lumbar spine: MD=-1.62%, 95% CI=-2.30, -0.95%, I2=93%; total hip: MD=-1.75%, 95% CI=-2.08, -1.42%, I2=83%; femoral neck: MD=-1.26%, 95% CI=-2.15, -0.38%, I2=43%) in comparison to those not taking TDF. Eight studies reported on incident osteoporosis or low bone mass, with variable results. Pooled results from five PrEP studies showed that TDF was not associated with increased fractures compared with no PrEP (RR=1.12, 95% CI=0.752, 1.74, I2=26%). CONCLUSIONS: TDF caused greater decreases in BMD than did comparators when used for all three indications and the magnitude of this decrease was larger for HIV treatment compared with PrEP. Fractures were not increased among PrEP patients. The clinically significant BMD decline caused by TDF and current expansion of PrEP use suggest attention to the adverse bone effects of TDF will increase in importance.

Community-Directed Bacterial Sexually Transmitted Infection Testing Interventions Among Men Who Have Sex With Men: Protocol for an E-Delphi Study in Toronto, Canada.

BACKGROUND: HIV-positive and HIV-negative (gay, bisexual, and other) men who have sex with men (MSM) have experienced a dramatic increase in bacterial sexually transmitted infections (STIs)-syphilis, gonorrhea, and chlamydia. STI testing and treatment mitigate adverse health outcomes and substantially reduce transmission; yet, testing rates remain below recommended levels. Innovation is needed to produce the required increases in testing levels, frequency, and the use of appropriate testing technologies in ways that are engaging, nonstigmatizing, and acceptable to men. OBJECTIVE: The aim of this study is to build consensus with regard to interventions with the greatest potential for improving local STI testing services for MSM communities in Toronto, Canada. METHODS: Following a literature review of evidence regarding the effectiveness of novel testing interventions, and focus groups, and surveys to describe local barriers and facilitators of testing among MSM, we will conduct a Web-based, modified Delphi study (e-Delphi). We will form expert panels of community members and STI test providers. Panelists will rate potential interventions in terms of their priority, using a 7-point Likert scale from definitely not a priority to definitely a priority. They will also rank their preferences by selecting their top 3 preferred interventions. Surveys will be distributed in 3 rounds, with feedback on the distribution of responses from preceding rounds provided in rounds 2 and 3. We will define consensus as having ≥60% (18/30) members indicate a preference within 2 adjacent response points. Qualitative data on disagreements will be obtained using open-ended text responses to explain for ratings and rankings that are different from the majority. RESULTS: On the basis of a literature review and identification of barriers and facilitators to STI testing among community members and test providers in Toronto, we have selected 8 potential interventions for inclusion in the e-Delphi panel surveys. These include 4 interventions that streamline STI testing for asymptomatic individuals, 2 interventions that are targeted at clients and 2 interventions that are targeted at providers. CONCLUSIONS: Findings will provide community direction for informed decision making regarding the implementation of STI testing interventions in this setting. They will characterize the intervention climate for innovation to STI testing services, including perceived needs for changes to test delivery, relative priorities for change, and readiness for implementation. These methods may be transferable to other urban jurisdictions experiencing similar epidemics and for other contexts where stakeholder input is needed to manage sensitive areas of concern. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/13801.

Feasibility of vitamin D supplementation interventions to mitigate HIV pre-exposure prophylaxis-related bone mineral density loss: a cross-sectional survey.

BACKGROUND: Daily tenofovir disoproxil fumarate (TDF)/emtricitabine as HIV pre-exposure prophylaxis (PrEP) causes subclinical decreases in bone mineral density (BMD). We surveyed PrEP users to assess feasibility for a clinical trial of vitamin D supplementation to mitigate TDF-induced BMD loss. METHODS: We recruited participants using or starting PrEP in Toronto and Vancouver. The primary objective was to assess the acceptability of daily or weekly vitamin D supplementation. We also assessed the acceptability of calcium supplementation, existing use of non-pharmacological bone health interventions, prevalence of osteoporosis risk factors, and bone health knowledge (Osteoporosis Knowledge Test, OKT). RESULTS: Of 161 participants, 72.1% were current PrEP users, 18.0% were starting PrEP, and 9.9% did not indicate their PrEP status. All identified as males, 88.8% as gays, and 67.1% as Whites. Median (IQR) age was 32.0 (29.0, 40.0) years, and 62.1% reported family income $$60,000/year. Among those not already using the interventions, willingness to supplement with daily vitamin D, weekly vitamin D, or daily calcium was very high at 90.9%, 96.4%, and 93.0 %, respectively. Only 31.0% reported adequate dietary calcium intake, while 42.9% reported $1 osteoporosis risk factor (most commonly, alcohol and smoking). Overall bone health knowledge was low, as median (IQR) OKT score was 16/32. In post hoc comparisons, current PrEP users may have been more likely than new PrEP users to engage in bone loading exercise (Bone-specific Physical Activity Questionnaire score=12.5 vs 3.6, P=0.001) and have greater bone health knowledge (OKT=17 vs 14, P=0.08), but they had similar levels of current vitamin D supplementation (37.4% vs 21.4%, P=0.11), calcium supplementation (11.2% vs 13.8%, P=0.70), and adequate dietary calcium intake (32.7% vs 25.0%, P=0.43). DISCUSSION: The high acceptability of vitamin D and calcium supplementation in this cohort suggests that enrollment into a clinical trial of such interventions to mitigate PrEP-induced BMD loss is feasible.

Does maternal HSV-2 coinfection increase mother-to-child transmission of HIV? A systematic review.

BACKGROUND: Reducing HIV mother-to-child transmission (MTCT) is critical to ending the HIV pandemic. Reports suggest that herpes simplex virus-2 (HSV-2), a common coinfection in HIV-infected individuals, is associated with increased MTCT, but results have been conflicting. We conducted a systematic review of observational studies to quantify the magnitude of this relationship (PROSPERO no. CRD42016043315). METHODS: We searched Medline (1981 to June week 3, 2016), EMBASE (1981 to week 26, 2016), relevant conferences (2013-2016) and bibliographies of identified studies for cohort and case-control studies enrolling HIV-positive women during pregnancy or peripartum that quantified the effect of HSV-2 infection on MTCT. The primary outcome was the risk of perinatal HIV transmission associated with maternal HSV-2 status. Risk of bias was evaluated using a standardised tool, and results were meta-analysed where appropriate using a random-effects model, with studies weighted using the inverse variance method. RESULTS: From 2103 hits, 112 studies were considered for inclusion, and 10 were ultimately included. Of the included studies, three used a case-control design, three were retrospective cohorts and four were prospective cohorts. Risk of bias was low in three studies, moderate in six and high in one. The median sample size was 278.5 mother-infant pairs (range: 48-1513). The most common strategy for classifying maternal HSV-2 status was type-specific serology (n=6), followed by genital shedding (n=3) or genital culture (n=3), clinical diagnosis of herpes (n=2) or genital ulcer disease (n=1). Results from five studies that provided quantitative estimates of the association between HSV-2 seropositivity and MTCT were meta-analysed, yielding a pooled unadjusted OR=1.17 (95% CI=0.69 to 1.96, I2=58%). Three of these studies further considered key confounding variables, specifically antiretroviral use and/or viral load (n=3), and mode of delivery (n=2), yielding a pooled adjusted OR=1.57 (95% CI=1.17 to 2.11, I2=0). CONCLUSIONS: Maternal HSV-2 coinfection appears to be associated with increased perinatal HIV transmission. Further study of the effect of HSV-2 treatment on MTCT is warranted.

Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk.

INTRODUCTION: Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. METHODS: Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. RESULTS: Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were "optimal" candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3-2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2-2.3). The proportion of men who were "optimal" candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP. CONCLUSIONS: A higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers.

Preparing for pre-exposure prophylaxis: perceptions and readiness of Canadian pharmacists for the implementation of HIV pre-exposure prophylaxis.

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted.

Pre-exposure prophylaxis for sexually-acquired HIV risk management: a review.

Despite significant efforts, the rate of new HIV infections worldwide remains unacceptably high, highlighting the need for new HIV prevention strategies. HIV pre-exposure prophylaxis (PrEP) is a new approach that involves the ongoing use of antiretroviral medications by HIV-negative individuals to reduce the risk of HIV infection. The use of daily tenofovir/emtricitabine as oral PrEP was found to be effective in multiple placebo-controlled clinical trials and approved by the United States Food and Drug Administration. In addition, the Centers for Disease Control and Prevention in the United States and the World Health Organization have both released guidelines recommending the offer of oral PrEP to high-risk populations. The scale-up of PrEP is underway, but several implementation questions remain unanswered. Demonstration projects and open-label extensions of placebo-controlled trials are ongoing and hope to contribute to our understanding of PrEP use and delivery outside the randomized controlled trial setting. Evidence is beginning to emerge from these open-label studies and will be critical for guiding PrEP scale-up. Outside of such studies, PrEP uptake has been slow and several client- and provider-related barriers are limiting uptake. Maximizing the public health impact of PrEP will require rollout to be combined with interventions to promote uptake, support adherence, and prevent increases in risk behavior. Additional PrEP strategies are currently under investigation in placebo-controlled clinical trials and may be available in the future.

No impact of oral tenofovir disoproxil fumarate on herpes simplex virus shedding in HIV-infected adults.

OBJECTIVE: to determine the impact of oral tenofovir as part of combination antiretroviral therapy on asymptomatic herpes simplex virus (HSV) shedding. DESIGN: observational study of a cohort of HSV, HIV-1 co-infected adults. METHODS: HSV infection was diagnosed using type-specific serology (HerpeSelect ELISA, Focus Technologies). Asymptomatic HSV, HIV-1 co-infected individuals achieving HIV viral load below 50 copies/ml on antiretroviral therapy self-collected oral, genital and anal swabs daily for 28 days. Refrigerated specimens were dropped off weekly for HSV-1 and HSV-2 testing by polymerase chain reaction (PCR). Shedding rate was calculated as the proportion of days on which HSV PCR was positive. RESULTS: : Forty co-infected patients were enrolled, of whom 30 were HSV-2 seropositive. Tenofovir was part of the antiretroviral regimen in 22 of 40 (55%) participants overall and 17 of 30 (57%) of HSV-2 infected participants. The median (interquartile range) HSV-2 shedding rate among HSV-2 seropositive participants was low, at 7.1% (0, 14.3) of specimen collection days, and did not differ between tenofovir users and nonusers (P = 0.36). There was no difference in the number of HSV-2 shedders in the tenofovir and nontenofovir groups (59 vs. 46%; P = 0.49). Rates of shedding for HSV-1 alone (P = 0.59), and for either HSV-1 or HSV-2 (P = 0.38), were also similar between tenofovir users and nonusers. CONCLUSION: although topical tenofovir 1% gel was associated with a significant decrease in HSV-2 acquisition among high-risk women in the recent CAPRISA 004 trial, in these preliminary data we did not observe an impact of oral tenofovir on HSV-2 or HSV-1 shedding rates among HIV, HSV co-infected asymptomatic adults.

Global plagues and the Global Fund: Challenges in the fight against HIV, TB and malaria.

BACKGROUND: Although a grossly disproportionate burden of disease from HIV/AIDS, TB and malaria remains in the Global South, these infectious diseases have finally risen to the top of the international agenda in recent years. Ideal strategies for combating these diseases must balance the advantages and disadvantages of 'vertical' disease control programs and 'horizontal' capacity-building approaches. DISCUSSION: The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) represents an important step forward in the struggle against these pathogens. While its goals are laudable, significant barriers persist. Most significant is the pitiful lack of funds committed by world governments, particularly those of the very G8 countries whose discussions gave rise to the Fund. A drastic scaling up of resources is the first clear requirement for the GFATM to live up to the international community's lofty intentions. A directly related issue is that of maintaining a strong commitment to the treatment of the three diseases along with traditional prevention approaches, with the ensuing debates over providing affordable access to medications in the face of the pharmaceutical industry's vigorous protection of patent rights. SUMMARY: At this early point in the Fund's history, it remains to be seen how these issues will be resolved at the programming level. Nevertheless, it is clear that significant structural changes are required in such domains as global spending priorities, debt relief, trade policy, and corporate responsibility. HIV/AIDS, tuberculosis and malaria are global problems borne of gross socioeconomic inequality, and their solutions require correspondingly geopolitical solutions.