Predictors of oral pre-exposure prophylaxis (PrEP) uptake among individuals in a HIV vaccine preparedness cohort in Masaka, Uganda.

ABSTRACT: Oral pre-exposure prophylaxis (PrEP) significantly reduces human immunodeficiency virus (HIV) acquisition risk. However, data on predictors of PrEP uptake in sub-Saharan Africa are limited. We assessed predictors of PrEP uptake among HIV-uninfected high risk individuals enrolled in a HIV vaccine preparedness study in Masaka, Uganda.Between July 2018 and October 2020, we recruited adults (18-40 years) from sex work hotspots along the trans-African highway and Lake Victoria fishing communities. We collected baseline data on socio-demographics and PrEP awareness, and provided HIV counselling and testing, information on PrEP, and PrEP referrals at quarterly visits. Urine pregnancy tests (women) and data collection on sexual risk behaviour and PrEP uptake were performed every 6 months. We analysed PrEP uptake among participants who had completed 6 months of follow-up.Of the 588 cohort participants, 362 (62%) were included in this analysis. Of these, 176 (49%) were female, 181 (50%) were aged ≤24 years, 104 (29%) worked in sex work hotspots, 74 (20%) were fisher folk. Only 75 (21%) participants initiated PrEP. Predictors of PrEP uptake included having ≥6 sex partners (adjusted odds ratio [aOR] = 2.29; 95% confidence interval [CI] 1.26-4.17), engaging in transactional sex (aOR = 2.23; 95% CI 0.95-5.20), and residence in a nonfishing community (aOR = 2.40; 95% CI 1.14-5.08). The commonest reasons for not starting PrEP were pill burden (38%) and needing more time to decide (27%).PrEP uptake was low and associated with HIV risk indicators in this cohort. Interventions are needed to improve access to PrEP especially in fishing communities.

Referral Linkage to Preexposure Prophylaxis Care and Persistence on Preexposure Prophylaxis in an Integrated Health Care System.

BACKGROUND: Successful linkage to preexposure prophylaxis (PrEP) and retention in care are important for HIV prevention. We examined gaps in PrEP care following referral and factors associated with PrEP linkage and persistence in an integrated health care system in the United States. METHODS: We identified individuals referred for PrEP from 2014 to 2017 at the Kaiser Permanente Southern California using electronic health records and assessed linkage to care, PrEP prescription orders and fills, and PrEP persistence (medication possession ratio ≥80%) in the year after the first fill. We evaluated demographic and clinical factors potentially associated with PrEP linkage and persistence using a series of multivariable modified Poisson regression models. RESULTS: Of 2995 referred individuals, 74.9% were linked to PrEP care. Nearly all those linked to care were prescribed PrEP and filled a prescription, but only 47.4% of those who filled a prescription were persistent on PrEP. Individuals aged <25 years (vs ≥25 years), female subjects (vs males), and individuals with high-deductible insurance (vs no high deductible) were less likely to be linked to care. Individuals aged <25 years and Hispanics (vs non-Hispanic whites) were less likely to be persistent. Those with alcohol use disorder were more likely to be linked to PrEP care but less likely to be persistent. New HIV diagnoses occurred in 38 individuals, and only 1 had PrEP in possession at diagnosis. CONCLUSIONS: We observed PrEP care gaps and disparities among individuals referred for PrEP. Patient-centered interventions are needed in primary care to address barriers to successful PrEP linkage and persistence.

Education, Perceptions, and Delivery: Factors Shaping the Perceived Role in the Pre-Exposure Prophylaxis (PrEP) Care Continuum Among a Sample of Osteopathic Medical Students.

Pre-exposure prophylaxis (PrEP) uptake has been suboptimal despite its demonstrated efficacy in reducing the risk of HIV acquisition. Medical education is one distal determinant that shapes medical providers' perceived role in the PrEP care continuum. However, there is limited understanding of how osteopathic medical students and those wanting to practice in rural areas perceive their role in the PrEP care continuum in the domains of PrEP awareness, uptake, and adherence and retention. Twenty-one semistructured interviews were conducted (March 2019-April 2020) to assess what shapes osteopathic medical students' perceived role in the PrEP care continuum. Participants noted a lack of adequate sexual health training, personal perceptions concerning PrEP use, and ambiguity concerning which of the medical specialties should deliver PrEP. Osteopathic medical schools can incorporate more inclusive and holistic sexual health and PrEP curricula to address these barriers and better prepare osteopathic medical students for their future role in the PrEP care continuum.

Directing the Antiretroviral Drugs to the Brain Reservoir: A Nanoformulation Approach for NeuroAIDS.

BACKGROUND: Human immunodeficiency virus (HIV)/AIDS is one of the principal concerns contributing to the global burden and the accompanying deleterious outcomes could not be left unattended. Despite significant advances and innovative research being conducted throughout the globe in order to improve the therapeutic profile of conventionally available antiretroviral (ARV) drugs in the eradication of HIV virus reservoirs, its penetration across the blood-brain barrier (BBB) is still a formidable mission. This makes the central nervous system a dominant and vulnerable site for virus propagation, which ultimately affects the therapeutic potential of the drug administered. Therefore there is an upsurge in the prerequisite of novel technologies to come into play, paving the way for nanotechnology. METHODS: This review primarily provides a comprehensive outline and emphasizes on the nanotechnological techniques employed for the delivery of ARV drugs and their stupendous advantages in overcoming the hurdles associated with the same. RESULTS: The nanotechnological approach bears the potential of site-specific delivery across the BBB via targeting explicit transport processes and provides a sustained release mechanism. Furthermore, different routes of administration explored have also yielded beneficial outcomes for the delivery of ARV drugs. CONCLUSION: The futuristic holistic nanotechnology methods, however, should focus on increasing drug trafficking and permeability across the BBB to ameliorate the therapeutic effect of ARV drugs. Additionally, the domain warrants clinical studies to be undertaken to make the technology commercially viable and a success to deal with the problems of the treatment strategy.

Emergence of Nanotechnology to Fight HIV Sexual Transmission: The Trip of G2-S16 Polyanionic Carbosilane Dendrimer to Possible Pre-Clinical Trials.

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.

Prescribing rates and characteristics of recipients of tenofovir-containing regimens before and after market entry of tenofovir alafenamide.

BACKGROUND: Tenofovir alafenamide (TAF) is a new formulation of tenofovir disoproxil fumarate (TDF) that was approved in 2015. While clinical trial evidence suggests that TAF has more favorable outcomes related to kidney injury and loss of bone mineral density, TAF also leads to higher lipid levels compared with TDF. OBJECTIVES: To (a) determine prescribing rates of TDF and TAF among new recipients from 2014 to 2018 in a large academic health system and (b) compare baseline patient characteristics of those newly prescribed TDF versus TAF before and after the approval of TAF in November 2015. METHODS: Electronic health record data were used to identify new recipients of TDF or TAF from 2014 to 2018 and describe their total monthly TDF and TAF prescriptions by indication. Patient characteristics were compared among new recipients of TDF before November 2015, new recipients of TDF after November 2015, and new recipients of TAF. RESULTS: Monthly TAF prescribing rates increased to match TDF prescribing rates by April 2018 (82 vs. 88 prescriptions per month). TAF recipients and new recipients of TDF before November 2015 had similar racial distributions; both of these groups were more likely to be Black compared with new recipients of TDF after November 2015 (55% and 53% vs. 37%; P < 0.0001). TAF recipients also tended to have more comorbidities, including chronic kidney disease (7% vs. 2% and 2%; P < 0.0001), hepatitis C virus (8% vs. 5% and 3%; P < 0.0001), diabetes (13% vs. 5% and 6%; P < 0.0001), hypertension (27% vs. 13% and 13%; P < 0.0001), coronary artery disease (5% vs. 3% and 2%; P < 0.0001), hyperlipidemia (21% vs. 6% and 7%; P < 0.0001), and congestive heart failure (3% vs. 1% and 1%; P < 0.0001), compared with both new recipients of TDF before and after November 2015. CONCLUSIONS: TAF prescribing rates grew substantially in the 2.5 years after FDA approval. TAF is being prescribed more often than TDF in patients with chronic kidney disease and in patients with cardiovascular disease, suggesting that prescribers may be prioritizing the kidney safety profile over the effect on lipids. DISCLOSURES: This work was supported by the Duke Clinical Research Institute Executive Director's Pathway for Supplemental Funding. The research team received additional support from the National Institute of Diabetes, Digestive, and Kidney Disease R01DK112258 and P01DK056492 (CW) and from the National Institute of Allergy and Infectious Diseases 5T32AI100851 (MHM). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Hung reports past employment by Blue Cross Blue Shield Association and CVS Health and a grant from Pharmaceutical Research and Manufacturers of America (PhRMA), unrelated to this work. The other authors have nothing to disclose. This work was accepted as a poster presentation for the AMCP Nexus 2020 Virtual, October 19-23, 2020.

An update on drug-drug interactions between antiretroviral therapies and drugs of abuse in HIV systems.

INTRODUCTION: While considerable progress has been made in the fight against HIV/AIDS, to date there has not been a cure, and millions of people around the world are currently living with HIV/AIDS. People living with HIV/AIDS have substance abuse disorders at higher rates than non-infected individuals, which puts them at an increased risk of drug-drug interactions. AREAS COVERED: Potential drug-drug interactions are reviewed for a variety of potential drugs of abuse, both licit and illicit. These drugs include alcohol, cigarettes or other nicotine delivery systems, methamphetamine, cocaine, opioids, and marijuana. Potential interactions include decreased adherence, modulation of drug transporters, or modulation of metabolic enzymes. We also review the relative incidence of the use of these drugs of abuse in People living with HIV/AIDS. EXPERT OPINION: Despite considerable improvements in outcomes, disparities in outcomes between PLWHA who use drugs of abuse, vs those who do not still exist. It is of critical necessity to improve outcomes in these patients and to work with them to stop abusing drugs of abuse.

Integrated Pharmacy and PrEP Navigation Services to Support PrEP Uptake: A Quality Improvement Project.

Preexposure prophylaxis (PrEP) is highly effective in preventing HIV among both men and women, with the reduction in risk directly linked to medication adherence. Navigation services and other adherence interventions have demonstrated efficacy in medication uptake; however, their use may not be fully integrated into clinic operations or their roles clearly defined. This quality improvement (QI) project developed an evidenced-based PrEP Navigation (PN) tool to identify patient-reported barriers to uptake and to support process improvement at a large community health center in Washington, DC. Outcomes related to patient-reported barriers, patient demographics, and time to medication pickup from the pharmacy were measured before and after implementation. A total of 198 patients were included in this analysis. Mean days from initial prescription to medication pickup was reduced by 1.42 days (p = .030) following PN tool implementation. The evidenced-based PN tool is modifiable to the needs of the individual clinic and the patients they care for to support wide-scale PrEP uptake and continuous system process improvements.

Integrating HIV Pre-Exposure Prophylaxis into Family Planning Care: A RE-AIM Framework Evaluation.

We aimed to systematically evaluate the feasibility of integrating HIV prevention services, including pre-exposure prophylaxis (PrEP), into a family planning setting in a high-prevalence community. We used the RE-AIM Framework (Reach, Efficacy, Adoption, Implementation, Maintenance) to evaluate the integration of HIV prevention services into a family planning clinic over 6 months. Before the integration, PrEP was not offered. We implemented a staff training program on HIV PrEP. We determined the proportion of women presenting to the clinic who were screened, eligible for, and initiated PrEP through chart review. We assessed staff comfort with PrEP pre- and post-integration. We compared planned and actual implementation, interviewed staff to determine barriers and facilitators, and tracked systems adaptations. We assessed maintenance of PrEP after the study concluded. There were 640 clinical encounters for 515 patients; the rate of HIV counseling and PrEP screening was 50%. The rate was 10% in month 1 and peaked to 65% in month 3. Nearly all screened patients were eligible for PrEP (98.4%) and 15 patients (6%) initiated PrEP. Staff knowledge and comfort discussing PrEP improved after education. Facilitators included partnering with local experts, continuing education, clinical tools for providers, and patient education materials. Barriers included competing priorities during clinical encounters, limited woman-centered patient education materials, and insurance-related barriers. Embedding HIV prevention services in the family planning setting was feasible in this pilot. The proportion of women screened for PrEP rapidly increased. In this high HIV prevalence community, nearly all screened women were eligible and 6% initiated PrEP.

Brief Report: Associations Between Self-Reported Substance Use Behaviors and PrEP Acceptance and Adherence Among Black MSM in the HPTN 073 Study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is efficacious for HIV prevention. Black men who have sex with men (MSM) accounted for the largest proportion of new HIV diagnoses in the United States relative to other racial/ethnic groups. Black MSM who use substances are at an increased risk for HIV infection and are ideal candidates for PrEP, but barriers to maintaining PrEP adherence remain a concern. We assessed whether substance use behaviors are associated with initiation and adherence to PrEP among a sample of black MSM in the United States. METHODS: Data for this analysis come from the HIV Prevention Trails Network Study 073 (HPTN 073). Substance use behaviors-including alcohol, marijuana, poppers (ie, alkyl nitrites), and stimulants (ie, methamphetamine/cocaine use) including use of these substances before/during condomless anal intercourse (CAI)-were assessed longitudinally through self-report. PrEP adherence was assessed by pharmacological testing in blood. Generalized estimating equations were used to evaluate association between substance use behaviors and PrEP initiation and adherence. RESULTS: Among 226 HIV-negative black MSM, the majority (60%) were 25+ years of age. Most of the substance use behaviors were not significantly associated with PrEP initiation or adherence. However, stimulant use before/during CAI was significantly associated with lower odds of PrEP adherence (adjusted odds ratio = 0.21, 95% confidence interval = 0.07 to 0.61; P = <0.01). CONCLUSIONS: These findings suggest that PrEP adherence is feasible among black MSM who use substances. However, black MSM who engage in stimulant use before/during CAI may present a unique group for additional study and support with enhanced behavioral health and support services.

Development of a pseudovirus assay and evaluation to screen natural products for inhibition of HIV-1 subtype C reverse transcriptase.

ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal plants are used in the management of Human Immunodeficiency Virus and Acquired Immunodeficiency Syndrome (HIV/AIDS) in many developing country settings where HIV-1 subtype C drives the epidemic. Efforts to identify plant derived molecules with anti-HIV properties require reproducible assay systems for routine screening of selected plant compounds. Although a number of standardized HIV-1 pseudoviruses have been generated to assess infectivity, replicability or reproducibility, HIV-1 subtype C (HIV-1-C) pseudoviruses have not been comprehensively characterized to identify inhibitory plant substances. AIM OF THE STUDY: The current study aimed at developing an HIV-1-C pseudovirus assay, and evaluate plant substances targeting reverse transcriptase (RT) activity. MATERIALS AND METHODS: HIV-1 subtype C pseudoviruses containing a luciferase reporter gene were generated by transfection of human 293T cells. HIV-1 subtype B (HIV-1-B) wild type pseudoviruses and mutants resistant to nucleoside and non-nucleoside RT inhibitors were also generated and used as controls. Selected plant substances and the RT inhibitors Zidovudine (AZT) and Nevirapine (NVP), were used to evaluate inhibition. Pseudovirus infectivity was determined by luciferase measurement in CF2/CD4+/CCR5 cells, and cytotoxicity was determined using the MTT assay. AZT and NVP inhibited wild type pseudoviruses in a dose dependent manner, with IC50 values in the nanomolar range. RESULTS: Pseudoviruses harbouring RT drug resistance mutations were poorly suppressed by AZT and NVP. Catechin, obtained from Peltophorum africanum inhibited HIV-1-C and HIV-1-B pseudoviruses with selective indices of 6304 µM (IC50: 0.49 µM, CC50: 3089 µM) and 1343 µM (IC50: 2.3 µM, CC50: 3089 µM), respectively; while the methanol root crude extract of Elaeodendron transvaalense gave IC50 values of 11.11 µg/ml and 16.86 µg/ml, respectively. CONCLUSION: The developed HIV-1-C pseudovirus assay can be used to screen plant substances for RT inhibition, and may have utility in settings with limited access to high level biosafety facilities.

Interactions between antiretroviral therapy and complementary and alternative medicine: a narrative review.

BACKGROUND: The use of complementary and alternative medicine including herbal medicine (phytotherapy), vitamins, minerals and food supplements is frequent among people living with HIV/AIDS (PLWHAs) who take antiretroviral (ARV) drugs, but is often not known by their prescribing physicians. Some drug-supplement combinations may result in clinically meaningful interactions. AIMS: In this literature review, we aimed to investigate the evidence for complementary and alternative medicine interactions with ARVs. SOURCES: A bibliographic search of all in vitro, human studies and case reports of the PubMed database was performed to assess the risk of interactions between complementary and alternative self-medication products and ARVs. The 'HIV drug interaction' (https://www.hiv-druginteractions.org) and 'Natural medicines comprehensive database' (https://naturalmedicines.therapeuticresearch.com) interaction checkers were also analysed. CONTENT: St John's wort, some forms of garlic, grapefruit and red rice yeast are known to have significant interaction and thus should not be co-administered, or should be used with caution with certain ARV classes. Data on other plant-based supplements come from in vitro studies or very small size in vivo studies and are thus insufficient to conclude the real in vivo impact in case of concomitant administration with ARVs. Some polyvalent minerals such as calcium, magnesium, and iron salts can reduce the absorption of integrase inhibitors by chelation. Potential interactions with vitamin C and quercetin with some ARVs should be noted and efficacy and tolerance of the treatment should be monitored. IMPLICATIONS: This review shows the importance of screening all PLWHAs for complementary and alternative medicine use to prevent treatment failure or adverse effects related to an interaction with ARVs. Further human studies are warranted to describe the clinical significance of in vitro interactions between numerous complementary and alternative medicine and ARVs.

Estimating HIV Management and Comorbidity Costs Among Aging HIV Patients in the United States: A Systematic Review.

BACKGROUND: As life expectancy of patients infected with human immunodeficiency virus (HIV) approaches that of the general population, the composition of HIV management costs is likely to change. OBJECTIVES: To (a) review treatment and disease management costs in HIV, including costs of adverse events (AEs) related to antiretroviral therapy (ART) and long-term toxicities, and (b) explore the evolving cost drivers. METHODS: A targeted literature review between January 2012 and November 2017 was conducted using PubMed and major conferences. Articles reporting U.S. costs of HIV management, acquired immunodeficiency syndrome (AIDS)-defining events, end of life care, and ART-associated comorbidities such as cardiovascular disease (CVD), chronic kidney disease (CKD), and osteoporosis were included. All costs were inflated to 2017 U.S. dollars. A Markov model-based analysis was conducted to estimate the effect of increased life expectancy on costs associated with HIV treatment and management. RESULTS: 22 studies describing HIV costs in the United States were identified, comprising 16 cost-effectiveness analysis studies, 5 retrospective analyses of health care utilization, and 1 cost analysis in a resource-limited setting. Management costs per patient per month, including routine care costs (on/off ART), non-HIV medication, opportunistic infection prophylaxis, inpatient utilization, outpatient utilization, and emergency department utilization were reported as CD4+ cell-based health state costs ranging from $1,192 for patients with CD4 > 500 cells/mm3 to $2,873 for patients with CD4 < 50 cells/mm3. Event costs for AEs ranged from $0 for headache, pain, vomiting, and lipodystrophy to $31,545 for myocardial infarction. The mean monthly per-patient costs for CVD management, CKD management, and osteoporosis were $5,898, $6,108, and $4,365, respectively. Improvements in life expectancy, approaching that of the general population in 2018, are projected to increase ART-related and AE costs by 35.4% and comorbidity costs by 175.8% compared with estimated costs with HIV life expectancy observed in 1996. CONCLUSIONS: This study identified and summarized holistic cost estimates appropriate for use within U.S. HIV cost-effectiveness analyses and demonstrates an increasing contribution of comorbidity outcomes, primarily associated with aging in addition to long-term treatment with ART, not typically evaluated in contemporary HIV cost-effectiveness analyses. DISCLOSURES: This analysis was sponsored by ViiV Healthcare, which had no role in the analyses and interpretation of study results. Ward, Sugrue, Hayward, and McEwan are employees of HEOR Ltd, which received funding from ViiV Healthcare to conduct this study. Anderson is an employee of GlaxoSmithKline and holds shares in the company. Punekar and Oglesby are employees of ViiV Healthcare and hold shares in GlaxoSmithKline. Lopes was employed by ViiV Healthcare at the time of the study and holds shares in GlaxoSmithKline.

The Effect of an Integrated Health System Specialty Pharmacy on HIV Antiretroviral Therapy Adherence, Viral Suppression, and CD4 Count in an Outpatient Infectious Disease Clinic.

BACKGROUND: Adherence to antiretroviral (ARV) therapy is critical in order to achieve and maintain viral suppression and improve immune function. Clinical pharmacists and pharmacies focused on human immunodeficiency virus (HIV) have demonstrated the ability to increase ARV medication adherence and subsequently have a positive effect on these lab markers. OBJECTIVES: To evaluate the effect of an integrated health system specialty pharmacy service with a clinic-embedded, HIV-trained pharmacist and pharmacy technician on ARV medication adherence rate, viral load, and CD4 count. METHODS: This was a single-center, retrospective cohort study conducted from August 7, 2017, to June 30, 2018, at an indigent outpatient infectious disease clinic within Atrium Health (AH), a not-for-profit health system based in Charlotte, NC. The intervention group (opt-in group) received HIV patient care that involved the health system specialty pharmacy service. Once a patient was enrolled in the specialty pharmacy service, medication reconciliation was completed by the pharmacist, financial assistance and prior authorizations were completed if needed; prescriptions were delivered to the patient; and monthly refills calls were conducted to assess adherence, tolerability, and medication changes. The control group (opt-out group) received HIV patient care that did not incorporate the health system specialty pharmacy. The primary endpoints were medication adherence, viral suppression, and CD4 counts. Within-group comparisons from baseline to follow-up were made along with group-to-group comparisons. Adherence was calculated using medication possession ratio. RESULTS: For those patients using Atrium Health Specialty Pharmacy Service (AH SPS; n = 46), the overall median adherence rate was higher at 100% versus only 94% for those patients (n = 50) that opted out of the service (P < 0.01). All but 3 patients (21.7% at baseline vs. 6.5% at follow-up, P = 0.03) using AH SPS reached viral suppression, and all but 1 had improved immune function with a CD4 count of 200 or greater by the end of the observation period (P = 0.03). The change in viral suppression and CD4 count of 200 or greater was not statistically improved between baseline and follow-up in those opting out of using AH SPS. When comparing the 2 groups at reaching these endpoints, there was no statistically significant difference in viral suppression and CD4 count. CONCLUSIONS: AH SPS was able to demonstrate improved ARV adherence in those patients using an integrated specialty pharmacy with an embedded pharmacy team, coordinated monthly medication delivery, and refill reminder and adherence calls. This in turn led to improved viral suppression and immune markers by the end of the observation window for patients using AH SPS. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

Improving Medication Adherence Among Drug-Using HIV-Infected Formerly Incarcerated Individuals: A Pilot Test of Two Interventions.

Incarcerated individuals in the United States are reportedly four times more likely to be infected with HIV than members of the general population, and a substantial proportion have a history of drug use. Postincarceration, many struggle to maintain their antiretroviral therapy (ART) regimen. This pilot study tested the potential performance of two ART adherence interventions, Project ADHerence Education and Risk Evaluation (ADHERE) and Medication Adherence and Care Engagement (MACE) among drug-using HIV-infected formerly incarcerated individuals in New York City. Thirty participants were randomized and completed the ADHERE or MACE intervention. Participants were interviewed and had their blood drawn for viral load testing at baseline and 3 months postintervention. Our findings suggest that drug-using HIV-infected formerly incarcerated individuals can benefit from brief ART adherence interventions. They also suggest that marijuana use may not have a negative impact on ART adherence.

Resonance of Periodic Combination Antiviral Therapy and Intracellular Delays in Virus Model.

There is a substantial interest in detailed models of viral infection and antiviral drug kinetics in order to optimize the treatment against viruses such as HIV. In this paper, we study within-viral dynamics under general intracellular distributed delays and periodic combination antiviral therapy. The basic reproduction number [Formula: see text] is established as a global threshold determining extinction versus persistence, and spectral methods are utilized for analytical and numerical computations of [Formula: see text]. We derive the critical maturation delay for virus and optimal phase difference between sinusoidally varying drug efficacies under various intracellular delays. Furthermore, numerical simulations are conducted utilizing realistic pharmacokinetics and gamma-distributed viral production delays for HIV. Our results demonstrate that the relative timing of the key viral replication cycle steps and periodic antiviral treatment schedule involving distinct drugs all can interact to critically affect the overall viral dynamics.

Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1.

PURPOSE OF REVIEW: To discuss the potential role of islatravir (ISL), a novel reverse transcriptase translocation inhibitor, in the treatment and prevention of human immunodeficiency virus type 1 (HIV-1) infection. RECENT FINDINGS: Islatravir (4'-ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591) is a long-acting first-in-class nucleoside reverse transcriptase translocation inhibitor with the potential for versatile dosing routes and dosing intervals. It demonstrated robust antiviral activity when dosed once daily and once weekly in HIV-1-infected individuals and SIV-infected rhesus macaques. In clinical trials of ISL in combination with doravirine and lamivudine, daily oral administration resulted in high levels of virologic suppression in HIV-infected individuals. In preclinical studies, ISL dosed orally once-weekly as preexposure prophylaxis (PrEP), protected rhesus macaques against SHIV infection via the mucosal route in the low-dose rectal challenge model. Most recently, data in healthy HIV-1-uninfected individuals demonstrated the feasibility of formulating of ISL as an implant. In these studies, levels of intracellular ISL-triphosphate were consistent with the potential for a once-yearly implantable administration of ISL as PrEP. SUMMARY: Islatravir is a promising new agent for both the treatment and prevention of HIV-1 infection.

Successful use of once-daily high-dose darunavir and dolutegravir in multidrug-resistant HIV.

WHAT IS KNOWN AND OBJECTIVE?: Antiretroviral (ARV) resistance may result during periods of consistently poor adherence. We report the successful use of a novel once-daily (QD) ARV regimen in a patient with multidrug-resistant (MDR) HIV. CASE SUMMARY: Once-daily darunavir 1200 mg/ritonavir 100 mg, dolutegravir and emtricitabine/tenofovir alafenamide was initiated with directly observed therapy. With the assistance of therapeutic drug monitoring, dolutegravir dosing was increased to 150 mg daily. The patient maintained virologic suppression for 18 months. WHAT IS NEW AND CONCLUSIONS?: In this case, QD darunavir/ritonavir achieved similar trough concentrations to twice daily dosing with dolutegravir dose titration necessitated and resulted in HIV virologic control.

Preferences for Pre-exposure Prophylaxis Service Delivery Among Female Sex Workers in Malawi: A Discrete Choice Experiment.

Female sex workers (FSW) in Malawi have among the highest HIV prevalence estimates worldwide. Daily oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, yet preferences for PrEP delivery among FSW are lacking. Eight focus group discussions, a literature review, and cognitive interviews were conducted to identify modifiable PrEP delivery attributes and inform discrete-choice experiment (DCE) development for FSW in Lilongwe. Enrolled FSW received an interviewer-assisted DCE. Data were analyzed using mixed logit regression. Dispensing location was most preferred, followed by the provision of additional services. Women preferred receiving PrEP at family planning clinics or non-governmental organization run drop-in centers. Cervical cancer screening was the most preferred additional service, while pregnancy testing and partner risk reduction counseling were less valued. This study was the first study to examine PrEP delivery preferences in Malawi using DCE-a powerful elicitation tool to apply to other key populations at risk for HIV.