Human Immunodeficiency Virus Prophylaxis Research Articles

Pre- and Post-Exposure Prophylaxis for HIV in Patients Taking Anti-Seizure Medications

The prevention of human immunodeficiency virus (HIV) infection has recently emphasized the use of pre- and post-exposure prophylaxis (PrEP and PEP), both of which were highly effective in prevention of HIV infection. Since the last published guidance regarding the cotreatment of people with anti-seizure medications (ASM) and antiretroviral treatments (ARTs) in 2012, both fields have numerous new medication options. Historically, cotreatment of HIV and seizures could be challenging with increased risk of virologic failure and barriers in access to health care due to global availability, social determinants of health, and stigma of both HIV and seizures. In this narrative review, we describe the data-driven and expected bidirectional pharmacokinetic (PK) interactions between guideline-based PrEP and PEP treatment and ASM, as well as overlapping side effects. There are many ASMs with no known interaction with PrEP or PEP regimens. The interactions focus on enzyme inducing ASMs, valproate, and lamotrigine. Most prominently, enzyme inducing ASMs lower serum levels of tenofovir-containing PrEP regimens and elements of PEP (dolutegravir, raltegravir, and ritonavir), which increased risk of virologic treatment failure in people with HIV but have unclear clinical significance on the effectiveness of PrEP and PEP. In addition, ritonavir treatment in PEP may significantly lower lamotrigine serum levels even during the 4 weeks of treatment, which may increase risk for breakthrough seizures during PEP and skin reactions after discontinuation of ritonavir. In addition to PK interactions, overlapping side effects are common including osteopenia, hepatic toxicity, and other gastrointestinal effects. This narrative review aims to be a resource for all clinicians prescribing ASMs so that they can create a welcoming environment to enable successful treatment of seizures and reduce the risk of HIV infection in people at risk. In addition, we highlight knowledge gaps and areas of unmet need that can be addressed with future studies.

Broadly neutralizing antibodies for HIV prevention: a comprehensive review and future perspectives.

SUMMARYThe human immunodeficiency virus (HIV) epidemic remains a formidable global health concern, with 39 million people living with the virus and 1.3 million new infections reported in 2022. Despite anti-retroviral therapy's effectiveness in pre-exposure prophylaxis, its global adoption is limited. Broadly neutralizing antibodies (bNAbs) offer an alternative strategy for HIV prevention through passive immunization. Historically, passive immunization has been efficacious in the treatment of various diseases ranging from oncology to infectious diseases. Early clinical trials suggest bNAbs are safe, tolerable, and capable of reducing HIV RNA levels. Although challenges such as bNAb resistance have been noted in phase I trials, ongoing research aims to assess the additive or synergistic benefits of combining multiple bNAbs. Researchers are exploring bispecific and trispecific antibodies, and fragment crystallizable region modifications to augment antibody efficacy and half-life. Moreover, the potential of other antibody isotypes like IgG3 and IgA is under investigation. While promising, the application of bNAbs faces economic and logistical barriers. High manufacturing costs, particularly in resource-limited settings, and logistical challenges like cold-chain requirements pose obstacles. Preliminary studies suggest cost-effectiveness, although this is contingent on various factors like efficacy and distribution. Technological advancements and strategic partnerships may mitigate some challenges, but issues like molecular aggregation remain. The World Health Organization has provided preferred product characteristics for bNAbs, focusing on optimizing their efficacy, safety, and accessibility. The integration of bNAbs in HIV prophylaxis necessitates a multi-faceted approach, considering economic, logistical, and scientific variables. This review comprehensively covers the historical context, current advancements, and future avenues of bNAbs in HIV prevention.

End of selection criteria based on sexual orientation: An international symposium on alternatives to donation deferral.

Until recently, gay, bisexual and other men who have sex with men (MSM) were deferred from donating blood for 3-12 months since the last male-to-male sexual contact. This MSM deferral has been discontinued by several high-income countries (HIC) that now perform gender-neutral donor selection. An international symposium (held on 20-04-2023) gathered experts from seven HICs to (1) discuss how this paradigm shift might affect the mitigation strategies for transfusion-transmitted infections and (2) address the challenges related to gender-neutral donor selection. Most countries employed a similar approach for implementing a gender-neutral donor selection policy: key stakeholders were consulted; the transition was bridged by time-limited deferrals; donor compliance was monitored; and questions or remarks on anal sex and the number and/or type of sexual partners were often added. Many countries have now adopted a gender-neutral approach in which questions on pre- and post-exposure prophylaxis for human immunodeficiency virus (HIV) have been added (or retained, when already in place). Other countries used mitigation strategies, such as plasma quarantine or pathogen reduction technologies for plasma and/or platelets. The experience with gender-neutral donor selection has been largely positive among the countries covered herein and seems to be acceptable to stakeholders, donors and staff. The post-implementation surveillance data collected so far appear reassuring with regards to safety, although longer observation periods are necessary. The putative risks associated with HIV antiretrovirals should be further investigated.

HIV Pre-Exposure Prophylaxis, Blood Donor Deferral, Occult Infection, and Risk of HIV Transmission by Transfusion: A Fine Balance Between Evidence-Based Donor Selection Criteria and Transfusion Safety.

Pre- and postexposure prophylaxis for human immunodeficiency virus (HIV) are key to reducing the transmission of this virus. Furthermore, low-toxicity, long-acting formulations provide additional clinical benefits, in particular easier adherence to treatment and prevention. However, breakthrough HIV infections can occur despite the use of pre-exposure prophylaxis (PrEP), mainly due to suboptimal adherence or multi-drug resistant HIV strains. Albeit rare, PrEP breakthrough infections have also been reported in fully adherent patients. Should such breakthrough infection occur in an eligible blood donor, PrEP might suppress viremia and delay antibody seroconversion, thereby masking the infection and increasing the risk of transfusion transmission. This possibility has raised concerns in the blood transfusion community but remains little documented. Therefore, a literature search was performed to assess the state of knowledge on the risk of PrEP breakthrough infection, with a particular focus on the risk of HIV entering the blood supply. Evidently, PrEP breakthrough infections are rare, although the risk is not zero. Moreover, a fraction of individuals - including blood donors - do not disclose PrEP use according to various surveys and measurements of HIV PrEP analytes. Additionally, viremia and seroconversion may remain undetectable or close to the limit of detection for a long time after cessation of PrEP, particularly with long-acting antiretrovirals. Therefore, current recommendations to defer donors for at least 3 months after the last dose of oral PrEP or 2 years for long-acting PrEP appear justified, as they safeguard the blood supply and public trust toward the system. These recommendations help to safeguard blood safety and public trust in the blood supply.

Identifying the barriers and facilitators to culturally responsive HIV and PrEP screening for racial, ethnic, sexual, and gender minoritized patients: A scoping review protocol.

While mainstream messaging about human immunodeficiency virus (HIV) disparities continues to highlight individual risk-taking behavior among historically marginalized groups, including racial, ethnic, sexual, and gender minoritized patients, the effect of structural factors and social determinants of health (SDOH) on morbidity and mortality remain underestimated. Systemic barriers, including a failure of adequate and acceptable screening, play a significant role in the disparate rates of disease. Primary care practitioner (PCP) competency in culturally responsive screening practices is key to reducing the impact of structural factors on HIV rates and outcomes. To address this issue, a scoping review will be performed to inform the development of a training series and social marketing campaign to improve the competency of PCPs in this area. This scoping review aims to analyze what recent literature identify as facilitators and barriers of culturally responsive HIV and pre-exposure prophylaxis (PrEP) screening practices for historically marginalized populations, specifically racial, ethnic, sexual, and gender minoritized groups. A secondary aim is to identify themes and gaps in the literature to help guide future opportunities for research. This scoping review will be performed following the framework set forth by Arksey and O'Malley and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR). Relevant studies between the years 2019-2022 will be identified using a rigorous search strategy across four databases: MEDLINE (via PubMed), Scopus, Cochrane (CENTRAL; via Wiley), and CINAHL (via EBSCO), using Boolean and Medical Subject Headings (MeSH) search terms. Studies will be uploaded to the data extraction tool Covidence to remove duplicates and perform a title/abstract screening, followed by a full-text screening and data extraction. Data will be extracted and analyzed for themes related to culturally responsive HIV and PrEP screening practices in clinical encounters with the identified target populations. Results will be reported according to PRISMA-ScR guidelines. To our knowledge, this is the first study to use scoping methods to investigate barriers and facilitators to culturally responsive HIV and PrEP screening practices for racial, ethnic, sexual, and gender minoritized populations. The limitations of this study include the analysis restrictions of a scoping review and the timeframe of this review. We anticipate that this study's findings will interest PCPs, public health professionals, community activists, patient populations, and researchers interested in culturally responsive care. The results of this scoping review will inform a practitioner-level intervention that will support culturally sensitive quality improvement of HIV-related prevention and care for patients from minoritized groups. Additionally, the themes and gaps found during analysis will guide future avenues of research related to this topic.

Prevalence of Mollicutes among men who have sex with men and transgender women aged 15 to 19 years in Salvador, North-eastern Brazil

BackgroundSome species of Mollicutes have been associated with different pathologies of the urogenital tract in humans, with a high prevalence among adult men who have sex with men (MSM) and transgender women (TGW). However, few studies have been performed to investigate its prevalence among adolescents. In this study, we estimated the initial prevalence of Mycoplasma genitalium (MG), Mycoplasma hominis (MH), Ureaplasma urealyticum (UU), and Ureaplasma parvum (UP); the rate of misdiagnosis at different anatomical sites; and the associated factors with positive tests for Mollicutes among MSM and TGW aged 15 to 19 years enrolled in the PrEP1519 study.MethodsPrEP-1519 is the first study to investigate the effectiveness of pre-exposure prophylaxis for human immunodeficiency virus among adolescent MSM and TGW aged 15 to 19 in Latin America. Oral, anal, and urethral swabs were taken from 246 adolescents upon enrolment in the study to detect MG, MH, UU, and UP by quantitative polymerase chain reaction (qPCR). Bivariate and multivariate analyses were conducted by Poisson regression and 95% confidence intervals (95% CI) were estimated.ResultsThe prevalence of Mollicutes was 32.1%. UU was the most prevalent species (20.7%), followed by MH (13.4%), MG (5.7%), and UP (3.2%); 67.3% of the positive samples would have been missed if only urethral samples had been taken. Receptive anal sex (prevalence ratio [PR] = 1.79; 95% CI = 1.07–3.01) and clinical suspicion of sexually transmitted infection (PR = 1.62; 95% CI = 1.01–2.61) were factors associated with the detection of Mollicutes in general. Group sex (PR = 1.98; 95% CI = 1.12–3.50) and receptive anal sex (PR = 2.36; 95% CI = 0.95–5.86) were associated with the detection of Mycoplasma spp. No sociodemographic, clinical, or behavioural variable was significantly associated with the detection of Ureaplasma spp.ConclusionsA high prevalence of Mollicutes was observed among adolescent MSM and TGW, especially at extragenital sites. Further research is required to understand the epidemiological profile of high-risk adolescents in different regions and contexts, and to investigate the pathogenesis of Mollicutes in the oral and anal mucosa before routine screening can be recommended in clinical practice.

Analysis of combined prevention measures on HIV/AIDS incidence in Brazil (1980-2020)

Introduction: The Human Immunodeficiency Virus (HIV) attacks the immune system, with acquired immunodeficiency syndrome (AIDS) being the most advanced clinical manifestation. Prevention strategies have evolved over time in response to scientific advancements. From an institutional perspective, the Unified Health System (SUS) provides tools for Combined Prevention to the entire Brazilian population, universally and free of charge. However, despite therapeutic advances, HIV/AIDS remains a significant public health problem. Objective: To analyze the impact of Combined Prevention measures on the incidence of HIV/AIDS in Brazil from 1980 to 2020. Methods: Quantitative, observational, longitudinal, and retrospective study. Descriptive and multivariate analyses were conducted, specifically employing linear regression techniques. The variables of interest included case incidence and the distribution of: tests for sexually transmitted infections (STIs), condoms, post-exposure prophylaxis for HIV (PEP), and pre-exposure prophylaxis for HIV (PrEP). Publicly available data were sourced from governmental repositories. Results: The country has accumulated 1,037,878 infection cases, with an average of 25,947 new cases per year. Regarding prophylaxis inputs, five out of six variables demonstrated a negative correlation with the incidence rate, with only the distribution of male condoms showing a positive correlation. The analysis of the effect of PrEP was not statistically significant. Conclusion: Brazil has reduced the incidence of the disease as Combined Prevention measures have advanced. More time is needed to assess the impact of PrEP on the incidence of new cases.

Cell and Tissue Specific Metabolism of Nucleoside and Nucleotide Drugs: Case Studies and Implications for Precision Medicine.

Many clinically used antiviral drugs are nucleoside or nucleotide analog drugs, which have a unique mechanism of action that requires intracellular phosphorylation. This dependence on intracellular activation presents novel challenges for the discovery and development of nucleoside/nucleotide analog drugs. Contrary to many small molecule drug development programs that rely on plasma pharmacokinetics and systemic exposures, the precise mechanisms that result in efficacious intracellular nucleoside triphosphate concentrations must be understood in the process of nucleoside/nucleotide drug development. The importance is highlighted here, using the following as case studies: the herpes treatment acyclovir, the cytomegalovirus therapy ganciclovir, and human immunodeficiency virus (HIV) treatments based on tenofovir, which are also in use for HIV prophylaxis. For each drug, the specificity of metabolism that results in its activation in different cells or tissues is discussed, and the implications explored. Acyclovir's dependence on a viral enzyme for activation provides selective pressure for resistance mutations. Ganciclovir is also dependent on a viral enzyme for activation, and suicide gene therapy capitalizes on that for a novel oncology treatment. The tissue of most relevance for tenofovir activation depends on its use as treatment or as prophylaxis, and the pharmacogenomics and drug-drug interactions in those tissues must be considered. Finally, differential metabolism of different tenofovir prodrugs and its effects on toxicity risk are explored. Taken together, these examples highlight the importance of understanding tissue specific metabolism for optimal use of nucleoside/nucleotide drugs in the clinic. SIGNIFICANCE STATEMENT: Nucleoside and nucleotide analogue drugs are cornerstones in current antiviral therapy and prevention efforts that require intracellular phosphorylation for activity. Understanding their cell and tissue specific metabolism enables their rational, precision use for maximum efficacy.

Potential of Long-Acting Products to Transform the Treatment and Prevention of Human Immunodeficiency Virus (HIV) in Infants, Children, and Adolescents.

Long-acting antiretroviral products have the potential to transform human immunodeficiency virus (HIV) prevention and treatment approaches in pediatric populations. Broadly neutralizing antibodies and/or long-acting antiretroviral formulations by injection could dramatically improve provision of HIV prophylaxis and/or early treatment to newborns and infants at risk of HIV infection. Challenges in daily oral antiretroviral administration to toddlers and school age children living with HIV may be relieved by use of long-acting formulations, but the pharmacokinetics and safety of these products in children must be studied before they can enter routine clinical use. Although some initial studies of broadly neutralizing antibodies and injectable long-acting agents in infants and young children are underway, more studies of these and other long-acting products are needed. For many adolescents, compliance with daily medication administration is especially challenging. Long-acting products hold particular promise for adolescents living with HIV as well as those at high risk of HIV acquisition, and adolescents can usually be included in the drug development pipeline simultaneously with adults. Long-acting products have the potential to provide alternatives to lifelong daily oral drug administration across the pediatric age spectrum, leading to more effective prevention and treatment of HIV infection in infants, children, and adolescents.

Paraphimosis as a complication of monkeypox infection

We discuss a case report of a 38-year-old uncircumcised male on pre-exposure prophylaxis for human immunodeficiency virus who presents to the emergency department for painful lesions over his penile region following unprotected sexual intercourse. Following the development of these lesions he developed painless, itchy pustules over his bilateral arms and back. He also had extensive pain and swelling over his penile region, which prevented him from unretracting his foreskin. Chlamydia trachomatis, Herpes simplex virus, Neisseria gonorrhoeae, and syphilis tests were negative. He was positive for orthopoxvirus using polymerase chain reaction. A diagnosis of paraphimosis as a complication of monkeypox infection was made.

Awareness of post exposure prophylaxis for human immunodeficiency virus among healthcare professionals in a tertiary care hospital in Telangana, South India

Background: India has the third highest number of people living with human immunodeficiency virus (PLHIV) population in the world. Health care personnel (HCP) are major risk group for acquiring HIV infection by accidental occupational exposure. Knowledge on post-exposure prophylaxis (PEP) holds the key to prevent new HIV infections and also helps in reduction of anxiety among HCP in case of accidental exposure. This study was designed to assess the awareness of PEP and to compare the levels of knowledge among various cadres of HCP.Methods: A cross sectional study was conducted on awareness of PEP among the health care personnel of sample size 360 in a tertiary care centre in urban South India. Universal sampling was done and data was collected for a period of three months. Analysis was done using the Epi info 7.2.Results: Knowledge of PEP among HCP was found to be 63.57%. Knowledge of PEP among groups of faculties, post graduate (PG) students, interns, nurses and lab technicians was found to be 73.5%, 70.9%, 62.8%, 56.9% and 42.2% respectively. There was poor knowledge among the most vulnerable groups i.e. nurses and lab technicians who handle the blood samples of number of PLHIV on a given day. There was a felt need among the faculty, PGs and interns for a refresher training every year on advances in HIV prophylaxis and treatment.Conclusions: This study has brought to light the lacunae in awareness of PEP for HIV among HCP. As India has a high prevalence of HIV, and occupational exposure is pretty much inevitable, there is a pressing need to plug the gaps in awareness of PEP.

Adverse Impact of Intimate Partner Violence Against HIV-Positive Women During Pregnancy and Post-Partum: Results From a Meta-Analysis of Observational Studies

Objectives: Intimate partner violence (IPV) against pregnant or human immunodeficiency virus (HIV)-positive women have been previously studied. However, data on the impact of IPV on HIV-positive pregnant women have not been systematically synthesized. We performed a meta-analysis to explore this issue and provide evidence regarding IPV prevention and HIV infection control. Method: The PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched. Studies that quantitatively assessed the association between IPV and its adverse impact on HIV-positive women during pregnancy and post-partum were eligible for inclusion. Pooled odds ratios (ORs) were calculated. Findings: Eight studies were identified to meet our eligibility criteria. The adverse impacts of IPV against HIV-positive pregnant women mainly included nonadherence to maternal antiretroviral treatment during pregnancy, nondisclosure of HIV-positive status to male partners, nonadherence to infant antiretroviral prophylaxis, and antenatal depression. IPV caused a 180% and 145% increase in the odds of antenatal depression and nonadherence to infant antiretroviral prophylaxis, respectively, among HIV-positive women, compared to the odds of their IPV-free counterparts [OR = 2.80, 95% confidence interval (CI): 1.66–4.74; OR = 2.45, 95% CI: 1.40–4.27]. Conclusion: Limited evidence has suggested that IPV against HIV-positive pregnant women caused maternal depression during pregnancy and led to the possible failure of HIV prophylaxis adherence in infants. Interventions to address IPV may ultimately reduce the risk of depression-related adverse birth outcomes and vertical transmission in infants exposed to maternal HIV. Prevention and control against IPV should be developed for HIV-positive pregnant women.

Occupational blood and body fluid exposure among emergency medical service providers in the eThekwini metropole of South Africa.

Emergency Medical Service (EMS) providers in South Africa are among health care workers (HCW) most at risk of contracting infectious diseases due to occupational exposure to blood and body fluids (BBF). While the austere, dynamic, and challenging nature of the prehospital environment appears to be one of the primary drivers to this risk, the growing prevalence of bloodborne infections within the country; particularly Hepatitis B, C and Human Immunodeficiency Virus (HIV), has inevitably compounded the problem. The aim of this study was to investigate the knowledge, practices, and prevalence of BBF exposure among EMS providers in the eThekwini metropole of KwaZulu-Natal, South Africa. This cross-sectional questionnaire-based study was completed by 96 randomly selected EMS providers who worked for the state-run ambulance service and were stationed within the eThekwini metropole. A total of 41 (42.7%) of the 96 respondents indicated memorable exposure to BBF at some point in their operational career. Exposure appeared to be mostly as a result of needlestick injuries (NSI) (63.4%), followed by BBF exposure into the eyes (19.5%). At the time of exposure, a total of 40 participants (97.6%) were wearing gloves, 22% (n=9) were wearing facemasks, and 9.8% (n=4) were wearing eye protection. Less than half of the respondents (46, 47.9%) were aware of existing EMS espoused BBF exposure policies, and 55 (57.3%) knew about post-exposure prophylaxis for HIV. Majority of the respondents (n=74; 77.1%) indicated that they always recapped needles, and 46.9% (n=45) dispose of sharps containers when completely full. The findings suggest that BBF related knowledge and practices among EMS providers working in the eThekwini metropole may be inadequate, and may increase the risk of blood exposure. In order to improve knowledge, immediate provision of EMS-specific BBF exposure training is required.

Healthcare Professionals' Practice of HIV Post-Exposure Prophylaxis in Clinical Settings in Karachi, Pakistan.

The human immunodeficiency virus (HIV) is an important public health concern that has become more prevalent in Pakistan in recent decades. Healthcare professionals (HCPs) are frequently exposed to many HIV-infected patients; as a result, they are more vulnerable to HIV infection due to occupational exposure. Hence, the current study was executed to evaluate HCPs’ knowledge, attitude and practice in terms of post-exposure prophylaxis (PEP) for HIV. This cross-sectional study was carried out in several clinical and laboratory settings of Karachi and the HCPs involved in treating patients were surveyed using a structured questionnaire. The Shapiro–Wilk test was performed to establish the normality of the variables. Pearson correlation was employed to identify the relationship between the independent variables considering p-values < 0.05 as statistically significant. A total of 578 filled forms were incorporated in the study with a response rate of 72.2%. Physicians and medical students (OR = 1.68; 95% CI = 1.16–2.24; p = 0.001) belonging to private work settings (OR = 1.84; 95% CI = 1.33–2.35; p < 0.003) indicated better knowledge. The majority, 407 (70.4%), of the respondents reported having been exposed to risky occupational circumstances during their professional life; however, 65.7% took PEP for HIV after exposure and only 56.8% completed the entire course. A statistically significant association was observed between experience (p = 0.004, CI = 0.14–0.72), job category (p = 0.0001, CI = 0.16–0.62) and frequency of exposure (p = 0.003, CI = 0.42–11.31) and reporting of occupational exposure. More than half (53.8%) of respondents stated that their institute has a policy for the management of HIV exposures; however, their response was significantly associated with their organization (p = 0.004). The current study shows adequate knowledge revealing a positive attitude among respondents; however, there was a gap between the knowledge and its practical application. Even though many of the HCPs had experienced risky HIV exposure, a lack of reporting was noted in the study.

Post-exposure prophylaxis for human immunodeficiency virus after sexual assault in a Midwestern U.S. emergency department.

Emergency departments (EDs) play an essential role in the timely initiation of HIV post-exposure prophylaxis (PEP) for sexual assault victims. Retrospective analysis of sexual assault victims evaluated and offered HIV PEP in an urban academic ED between January 1, 2005 and January 1, 2018. Data on demographics, comorbidities, nature of sexual assault, initial ED care, subsequent healthcare utilization within 28 days of initial ED visit, and evidence of seroconversion within 6 months of the initial ED visit were obtained. Predictors of subsequent ED visit and follow-up in the infectious diseases clinic were evaluated using logistic regression analysis. Four hundred twenty-three ED visits met criteria for inclusion in this study. Median age at ED presentation was 25 years (IQR 21-34 years), with the majority of victims being female (95.5%), Black (63.4%), unemployed (66.3%) and uninsured (53.9%); psychiatric comorbidities (38.8%) and substance abuse (23.6%) were common. About 87% of the patients accepted HIV PEP (368 of 423 ED visits). Age (OR 0.97, 95% CI 0.94-0.99, p = 0.025) and sexual assault involving >1 assailant (OR 0.48, 95% CI 0.26-0.88, p = 0.018) were associated with lower likelihood of HIV PEP acceptance. Ten patients (2.7%) followed up with the infectious disease clinic within 28 days of starting HIV PEP; 70 patients (19%) returned to the ED for care during the same time period. Psychiatric comorbidity (OR 2.48, 95% CI 1.43-4.30, p = 0.001) and anal penetration (OR 2.02, 95% CI 1.10-3.70, p = 0.024) were associated with greater likelihood of repeat ED visit; female gender (OR 0.30, 95% CI 0.11-0.85, p = 0.023) was associated with lower likelihood of repeat visit. Completion of HIV PEP was documented for 14 (3.3%) individuals. While ED patient acceptance of HIV PEP after sexual assault was high, infectious disease clinic follow-up and documented completion of PEP remained low. Innovative care models bridging EDs to outpatient clinics and community support services are needed to optimize transitions of care for sexual assault victims, including those receiving HIV PEP.

Exploration of pharmacist comfort with harm reduction behaviors: Cross-sectional latent class analysis

BackgroundPharmacists are positioned to play important roles in implementing evidence-based prevention and harm reduction approaches for opioid misuse and related health care outcomes such as human immunodeficiency virus (HIV) and hepatitis C. More research is needed to understand how best to facilitate harm reduction practices among pharmacists. ObjectivesThis hypothesis-generating study investigated (1) whether subgroups (latent classes) were observable among pharmacists based on self-reported comfort with specific harm reduction behaviors, (2) whether having reported expertise in key content areas was associated with any latent classes that might be identified, and (3) whether comfort and training were associated with actually having dispensed syringes for likely nonprescription drug use. MethodsThis was a statewide census of community managing pharmacists in Arizona conducted from December 2018 to May 2019. Participants reported their degree of comfort with 10 harm reduction behaviors, their expertise (e.g., recent continuing pharmacy education or specialization) in selected content areas, and their syringe dispensing behavior. Additional sociodemographic information was also collected. Subgroups related to harm reduction were computed using latent class analysis, and associations between study variables were assessed using the Fisher's exact tests. ResultsData suggested the existence of 4 latent, comfort-based harm reduction classes: high comfort, moderate comfort, and clinical comfort, and opioid prevention only. Reported expertise in pre-exposure prophylaxis for HIV was likely associated with harm reduction class. However, class membership was not associated with reporting having dispensed nonprescription syringes, although the single comfort item for syringe dispensing, by itself, was associated therewith. ConclusionComfort with harm reduction likely clusters, so pharmacists may be broadly comfortable with topics or methods of harm reduction; however, comfort with a specific harm reduction pharmacy practice may be a better predictor of engaging in that behavior than harm reduction comfort class. In contrast, strategies to improve comfort, such as intervention development, might successfully be informed by pharmacists’ latent class.

Naturally Occurring Mutations to Muscle-Type Creatine Kinase Impact Its Canonical and Pharmacological Activities in a Substrate-Dependent Manner In Vitro.

Tenofovir (TFV) is a key component of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). TFV is a nucleotide analog reverse-transcriptase inhibitor prodrug that requires two separate phosphorylation reactions by intracellular kinases to form the active metabolite tenofovir-diphosphate (TFV-DP). Muscle-type creatine kinase (CKM) has previously been demonstrated to be the kinase most responsible for the phosphorylation of tenofovir-monophosphate (TFV-MP) to the active metabolite in colon tissue. Because of the importance of CKM in TFV activation, genetic variation in CKM may contribute to interindividual variability in TFV-DP levels. In the present study, we report 10 naturally occurring CKM mutations that reduced TFV-MP phosphorylation in vitro: T35I, R43Q, I92M, H97Y, R130H, R132C, F169L, Y173C, W211R, V280L, and N286I. Interestingly, of these 10, only 4—R130H, R132C, W211R, and N286I—reduced both canonical CKM activities: ADP phosphorylation and ATP dephosphorylation. Although positions 130, 132, and 286 are located in the active site, the other mutations that resulted in decreased TFV-MP phosphorylation occur elsewhere in the protein structure. Four of these eight mutations—T35I, R43Q, I92M, and W211R—were found to decrease the thermal stability of the protein. Additionally, the W211R mutation was found to impact protein structure both locally and at a distance. These data suggest a substrate-specific effect such that certain mutations are tolerated for canonical activities while being deleterious toward the pharmacological activity of TFV activation, which could influence PrEP outcomes.SIGNIFICANCE STATEMENTMuscle-type creatine kinase (CKM) is important to the activation of tenofovir, a key component of HIV prophylaxis. This study demonstrates that naturally occurring CKM mutations impact enzyme function in a substrate-dependent manner such that some mutations that do not reduce canonical activities lead to reductions in the pharmacologically relevant activity. This finding at the intersection of drug metabolism and energy metabolism is important to the perspective on pharmacology of other drugs acted on by atypical drug-metabolizing enzymes.

Longitudinal Follow-Up of Blood Telomere Length in HIV-Exposed Uninfected Children Having Received One Year of Lopinavir/Ritonavir or Lamivudine as Prophylaxis.

Telomere shortening can be enhanced upon human immunodeficiency virus (HIV) infection and by antiretroviral (ARV) exposures. The aim of this study was to evaluate the acute and long-term effect on telomere shortening of two ARV prophylaxes, lopinavir/ritonavir (LPV/r) and lamivudine (3TC), administered to children who are HIV-exposed uninfected (CHEU) to prevent HIV acquisition through breastfeeding during the first year of life, and to investigate the relationship between telomere shortening and health outcomes at six years of age. We included 198 CHEU and measured telomere length at seven days of life, at week-50 and at six years (year-6) using quantitative polymerase chain reaction. At week-50, telomere shortening was observed among 44.3% of CHEU, irrespective of the prophylactic treatment. Furthermore, this telomere shortening was neither associated with poor growth indicators nor neuropsychological outcomes at year-6, except for motor abilities (MABC test n = 127, β = −3.61, 95%CI: −7.08, −0.14; p = 0.04). Safety data on telomere shortening for infant HIV prophylaxis are scarce. Its association with reduced motor abilities deserves further attention among CHEU but also HIV-infected children receiving ARV treatment.

Implementation and Access to Pre-exposure Prophylaxis for Human Immunodeficiency Virus by Men Who Have Sex With Men in Europe.

Pre-exposure prophylaxis (PrEP) is a significant public health intervention with proven efficacy and safety in the prevention of human immunodeficiency virus (HIV) infection, which has taken a considerable amount of time to reach Europe in relation to their transatlantic counterparts, namely, the United States of America (USA). There, it is perceived as being an essential prevention tool to be integrated within existing medical, behavioral and structural interventions in place for the management and containment of HIV infection in men who have sex with men (MSM). In a region such as Europe, with approximately double the USA population, it is estimated that not even 10% have proper access to PrEP, and given the lack of coordination with healthcare, taking PrEP has to be at their own expense. Here, we identify the reasons behind the 4-year lag in the approval of PrEP in the European Union/European Economic Area (and Europe in general) and explore the efficacy and effectiveness of PrEP needed to be confirmed with some implementation or demonstration studies conducted in the region. Independent of the data gathered, access of MSM to PrEP is far from ideal in Europe and much still needs to be done. The demonstration of the cost-effectiveness of PrEP alongside other social and behavioral factors needs to be addressed, while the clear populations within MSM that will benefit from this intervention are properly identified and make use of the latest recommendations of the World Health Organization that consider not only daily PrEP but also event-driven PrEP. The momentum for the proper implementation of PrEP in the EU is not lost, and with the existence of generics and even new formulations, there is a renewed opportunity for unleashing the public health benefits arising from this pharmacological tool with other interventions in place (e.g., condoms, testing, and counseling).

Silicone Induced Severe Hypercalcemia

Background: Silicone injections are becoming increasingly prevalent for cosmetic enhancement in the transgender population. We report a case of silicone-induced hypercalcemia to highlight the process of extra-renal production of 1,25-hydroxy (OH) vitamin D (calcitriol) and discuss the approaches in managing this rare entity. Clinical Case: A 51-year-old African American transgender female with a past medical history of human immunodeficiency virus (HIV) on antiretroviral therapy with undetectable viral load presented with right flank pain, nausea, and vomiting for one day. On examination, nodules were palpated in both breasts, left lateral hip, and the gluteal area had hyperpigmentation from silicone injections ten years ago. Calcium was elevated at 15.2 mg/dL (8.5–10.5) with albumin 3.8 g/dL (3.5–5), ionized calcium 7.4 mg/dL (4.64–5.28), phosphate 4.5 mg/dL (2.5–4.8) and creatinine of 3.2 mg/dL (0.4–1.4). Imaging revealed right ureteral calculi with hydronephrosis requiring stent placement.PTH was suppressed <5 pg/ml (12–72) and PTHrP were negative. Vitamin D 25 (OH) of 28 ng/mL (30–100) with elevated 1, 25 OH2 D3 144 pg/ml (19–79) and ACE 141 units/L (12–60) were suggestive of a granulomatous process. CT chest and abdomen without contrast did not show any hilar, mediastinal, or abdominal lymphadenopathy to suggest sarcoidosis or lymphoma, but numerous bilateral calcified masses were noted within the breasts consistent with silicone injections. Serum and urine electrophoresis were consistent with monoclonal gammopathy of undetermined significance. Patient deferred further evaluation (PET-CT and skin biopsy for granulomatous changes) as an outpatient.Calcium improved in 4 days to 10.5 mg/dL with intravenous hydration, calcitonin 260 units, IV furosemide 20 mg, and pamidronate of 60 mg. Despite a repeat dose of Pamidronate 60 mg a week later her calcium was rising again to 11.1 mg/dL. Plastic surgery evaluation concluded that due to extensive implants, surgery would be very disfiguring and challenging. She was reluctant to start prednisone as it may affect healing after surgery and the need for antibiotic prophylaxis for HIV, but she later agreed. Prednisone 20 mg daily was started for granulomatous disease and Calcium improved to 10.3 mg/dL. Conclusion/Clinical Lesson: Silicone Induced hypercalcemia is a rare entity with diagnostic and treatment dilemmas. Based on the few reported cases, silicone induced severe hypercalcemia is managed with IV hydration, denosumab, or zoledronic acid. However, glucocorticoids may maintain normocalcemia like in other granulomatous diseases. Removal of silicone implants may improve hypercalcemia, but it is challenging given the extent of implants, disfigurement, and possible disseminated disease and may not be curative. These aspects need to be considered in evaluating and management.