HIV Pre-Exposure Prophylaxis: New and Upcoming Drugs to Address the HIV Epidemic.

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) provides a critical intervention toward ending the HIV epidemic and protecting people with reasons to utilize PrEP. PrEP options continue to expand as new administration modalities offer the potential to tailor PrEP use for individual success. We have provided the evidence for new and emerging antiretroviral agents for PrEP (cabotegravir, lenacapavir, dapivirine, and broadly neutralizing antibodies), divided into pharmacology, animal model, and human data, accompanied by a summary and suggested place in therapy. Cabotegravir is a US Food and Drug Administration (FDA)-approved intramuscular injection given every 2 months with a strong body of evidence demonstrating efficacy for HIV PrEP, lenacapavir administered subcutaneously every 6 months is currently under investigation for HIV PrEP, dapivirine vaginal ring is an available PrEP option for women in certain areas of Africa, and broadly neutralizing monoclonal antibodies have been challenged in demonstrating efficacy in phase 1-2 study for HIV PrEP to date. Clinical literature for individual agents is discussed with data from major studies summarized in tables. This review provides a detailed overview of recently available and premier candidate PrEP drugs.

Lessons Learned from Programmatic Gains in HIV Service Delivery During the COVID-19 Pandemic - 41 PEPFAR-Supported Countries, 2020.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports country programs in identifying persons living with HIV infection (PLHIV), providing life-saving treatment, and reducing the spread of HIV in countries around the world (1,2). CDC used Monitoring, Evaluation, and Reporting (MER) data* to assess the extent to which COVID-19 mitigation strategies affected HIV service delivery across the HIV care continuum† globally during the first year of the COVID-19 pandemic. Indicators included the number of reported HIV-positive test results, the number of PLHIV who were receiving antiretroviral therapy (ART), and the rates of HIV viral load suppression. Percent change in performance was assessed between countries during the first 3 months of 2020, before COVID-19 mitigation efforts began (January-March 2020), and the last 3 months of the calendar year (October-December 2020). Data were reviewed for all 41 countries to assess total and country-level percent change for each indicator. Then, qualitative data were reviewed among countries in the upper quartile to assess specific strategies that contributed to programmatic gains. Overall, positive percent change was observed in PEPFAR-supported countries in HIV treatment (5%) and viral load suppression (2%) during 2020. Countries reporting the highest gains across the HIV care continuum during 2020 attributed successes to reducing or streamlining facility attendance through strategies such as enhancing index testing (offering of testing to the biologic children and partners of PLHIV)§ and community- and home-based testing; treatment delivery approaches; and improvements in data use through monitoring activities, systems, and data quality checks. Countries that reported program improvements during the first year of the COVID-19 pandemic offer important information about how lifesaving HIV treatment might be provided during a global public health crisis.

Prevalence, Anatomic Distribution, and Correlates of Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among a Cohort of Men Who Have Sex With Men in Hanoi, Vietnam.

BACKGROUND: Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) disproportionately affect men who have sex with men (MSM). Data on the prevalence, anatomical distribution, and correlates of NG and CT infections among MSM in Vietnam are limited. METHODS: Between July 2017 and April 2019, MSM 16 years or older without HIV were enrolled into an observational cohort study. Baseline data, including sociodemographics, sexual behavior, and HIV status, were collected. Testing for NG and CT were performed on urine, rectal, and pharyngeal specimens. Multivariate logistic regression models identified factors associated with NG and CT infections at baseline. RESULTS: In total, 1489 participants underwent NG/CT testing. The median age was 22 years (interquartile range, 20-26 years). There were 424 (28.5%) NG or CT infections: 322 (21.6%) with CT and 173 (11.6%) with NG. Rectal infections were most common for CT (73.9%), whereas pharyngeal infections were most common for NG (70.5%). Independent risk factors for CT or NG infection included ≥2 sex partners in the prior month (adjusted odds ratio [aOR], 2.04; 95% confidence interval [CI], 1.44-2.91), condomless anal sex (aOR, 1.44; 95% CI, 1.12-1.86), and meeting sex partners online (aOR, 1.35; 95% CI, 1.03-1.76). Recent genitourinary or rectal symptoms were not associated with infections. CONCLUSIONS: The overall and extragenital prevalences of NG and CT infections were high within this sample of young MSM without HIV in Hanoi. Testing limited to urethral specimens would have missed nearly three-quarters of CT and NG infections, supporting the need for routine testing at multiple anatomic sites.

Point-of-care program in HIV, tuberculosis, and associated conditions: A virtual global technical assistance platform to strengthen HIV and tuberculosis workforce capacity.

A global multi-disciplinary faculty was established to work collaboratively and provide virtual technical assistance, using a point-of-care continuing education model, to clinicians across the world engaged in the care of patients with either HIV infection or tuberculosis. Ancillary offerings included live or virtual lectures, case-based conferences, and courses. In spite of the considerable disruption of the program due to the COVID-19 pandemic, we engaged and assisted a substantial number of clinicians across the world and provided meaningful contributions to their continuous professional development and patient care. In light of the ongoing pandemic, virtual technical assistance models such as this should be scaled to continue essential high-quality HIV/TB services.

Substantial Need for Preexposure Prophylaxis Among Men Who Have Sex With Men in Hanoi, Vietnam.

ABSTRACT: We used data from the Health in Men-Hanoi cohort to determine the proportion of HIV-negative men who have sex with men with PrEP indications in Hanoi. Among 717 men who have sex with men, 537 (72.2% [66.6%-77.3%]) had ≥1 PrEP indication, signaling a substantial need for PrEP scale-up. Condomless anal intercourse was the most frequent indication (68.7% [60.3%-76.1%]), followed by previous/current sexually transmitted infection (59.4% [51.0%-67.2%]).

Embedding a Linkage to Preexposure Prophylaxis Care Intervention in Social Network Strategy and Partner Notification Services: Results From a Pilot Randomized Controlled Trial.

BACKGROUND: Increased preexposure prophylaxis (PrEP) uptake among black men who have sex with men and black transgender women (BMSM/TW) is needed to end the HIV epidemic. Embedding a brief intervention in network services that engage individuals in HIV transmission networks for HIV/ sexually transmitted infections testing may be an important strategy to accelerate PrEP uptake. SETTING: Partner Services PrEP study is a pilot, randomized, control trial to improve linkage to PrEP care among BMSM/TW presenting for network services in Chicago, IL, from 2015 to 2017. METHODS: BMSM/TW (N = 146) aged 18-40 years were recruited from network services (partners services and social network strategy services). Intervention participants developed an individualized linkage plan based on the information-motivation-behavioral skills model and received minibooster sessions. Control participants received treatment as usual. Sociodemographic, behavioral, and clinical factors were examined at baseline and 3- and 12-month postintervention. Intent-to-treat analyses examined linkage to PrEP care within 3-month postintervention (primary outcome). Secondary outcomes were PrEP initiation, time to linkage to PrEP care, and time to PrEP initiation. RESULTS: Compared with control participants, a significantly greater proportion of the intervention participants were linked to PrEP care within 3 months (24% vs. 11%; P = 0.04) and initiated PrEP (24% vs. 11%; P = 0.05). Among those linked to PrEP care within the study period, intervention participants were linked significantly sooner than control participants [median (interquartile range) days, 26.5 (6.0-141.8) vs. 191.5 (21.5-297.0); P = 0.05]. CONCLUSION: Study results support the preliminary efficacy of Partner Services PrEP to improve linkage to PrEP care and PrEP initiation among BMSM/TW.

Outcomes of Preexposure Prophylaxis Referrals From Public STI Clinics and Implications for the Preexposure Prophylaxis Continuum.

BACKGROUND: Human immunodeficiency virus preexposure prophylaxis (PrEP) uptake remains low in high-risk populations. Sexually transmitted infection (STI) clinics reach PrEP-eligible persons and may be ideal settings to model PrEP implementation. METHODS: Consenting PrEP-eligible patients identified at Chicago Department of Public Health STI Clinics were actively referred to PrEP partner sites between June 1, 2015, and May 31, 2016. Outcomes included successful contact by a partner site, linkage to a partner site, and receipt of a PrEP prescription. Bivariable and time to event analyses were conducted to determine significant associations of outcomes. RESULTS: One hundred thirty-seven patients were referred; 126 (92%) were men who have sex with men, and mean age was 29 years. Ninety-eight (72%) were contacted by a PrEP partner, 43 (31%) were linked, and 40 (29%) received a prescription. Individuals aged 25 years and older were more likely to link (odds ratio, 3.10; 95% confidence interval, 1.30-7.41) and receive a PrEP prescription (odds ratio, 2.70; 95% confidence interval, 1.12-6.45) compared with individuals 24 years and younger. The average time between each step was greater for those 24 years and younger compared with those aged 25 years and older for all steps. Time to event analyses revealed that those aged 25 years and older were significantly more likely to receive a prescription compared to those aged 24 years and younger (hazard ratio, 3.62; 95% risk limits, 1.47-8.92). CONCLUSIONS: Preexposure prophylaxis active referrals from STI clinics to partner sites are feasible, though drop out was prominent in the initial steps of the continuum. Youth were less likely to link or receive prescriptions, indicating the need for tailored interventions for this vulnerable population.

Trends in HIV Risk, Testing, and Treatment among MSM in Chicago 2004-2014: Implications for HIV Elimination Planning.

Men who have sex with men (MSM) in the USA continue to have high rates of HIV infection. Increasingly, in addition to behavioral factors, biomedical interventions have been found to play important roles in HIV prevention. In this analysis, we used four waves of cross-sectional data (2004, 2008, 2011, and 2014) from the National HIV Behavioral Surveillance System (NHBS) to examine trends in key behaviors and biomedical interventions among MSM in Chicago (N = 3298). Logistic regression was used to determine changes in behaviors and use of biomedical interventions. Condomless sex increased significantly in waves 3 and 4, compared to wave 1: wave 3 (AOR = 2.07; 95% CI 1.53, 2.78) and wave 4 (AOR = 2.19; 95% CI 1.62, 2.96). Compared to those aged 18-24, older participants were significantly less likely to be routinely tested for HIV: 30-39 (AOR = 0.63; 95% CI 0.48, 0.83), 40-49 (AOR = 0.40; 95% CI 0.29, 0.55), and >50 (AOR = 0.28; 95% CI 0.18, 0.43). Awareness of both post-exposure prophylaxis (PEP)(​AOR = 3.13; 95% CI 1.22, 8.03) and pre-exposure prophylaxis (PrEP)(​AOR = 10.02; 95% CI 2.95, 34.01) increased significantly in wave 4, compared to wave 3. These results suggest a potential increase in HIV rates among men with main and casual partners and should be monitored closely as PrEP becomes more widespread among MSM of all races and ethnicities in Chicago. This study also suggests that further analyses of the barriers to PEP and PreP uptake among high-risk populations are necessary.

Exploring Patterns of Awareness and Use of HIV Pre-Exposure Prophylaxis Among Young Men Who Have Sex with Men.

Pre-exposure prophylaxis (PrEP) has shown promise as a safe and effective HIV prevention strategy, but there is limited research on awareness and use among young men who have sex with men (YMSM). Using baseline data from the "Keep It Up! 2.0" randomized control trial, we examined differences in PrEP awareness and use among racially diverse YMSM (N = 759; mean age = 24.2 years). Participants were recruited from study sites in Atlanta, Chicago, and New York City, as well as through national advertising on social media applications. While 67.5 % of participants reported awareness of PrEP, 8.7 % indicated using the medication. Awareness, but not use, varied by demographic variables. PrEP-users had twice as many condomless anal sex partners (ERR = 2.05) and more condomless anal sex acts (ERR = 1.60) than non-users. Future research should aim to improve PrEP awareness and uptake among YMSM and address condom use.

Differences in Healthcare Access, Use, and Experiences Within a Community Sample of Racially Diverse Lesbian, Gay, Bisexual, Transgender, and Questioning Emerging Adults.

PURPOSE: Health services research involving lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) individuals has focused on differences in healthcare access, use, and experiences between cisgender, heterosexual adults and LGBTQ adults. Yet these factors may differ within the LGBTQ community and have not been well-studied among emerging adults (18-29 years), a group with unique barriers to healthcare. We sought to characterize healthcare challenges within a sample of LGBTQ emerging adults. METHODS: From 2012 to 2013, 206 participants aged 18-27 (86% racial/ethnic minority, 10% transgender) completed questionnaires assessing healthcare access, use, and experiences during a longitudinal study. Descriptive statistics established patterns of healthcare access, use, and experiences, and nonparametric tests examined differences related to sociodemographic variables, HIV status, sexual orientation identity, and gender identity. RESULTS: Overall, 68% of participants reported relatively easy access to care. White and bisexual participants reported higher rates of insurance than racial/ethnic minority (P = 0.01) and gay or lesbian participants (P = 0.005), respectively. Although most participants did not report having negative experiences in healthcare settings related to their LGBTQ identity, transgender participants were more likely to delay care (P < 0.001) and report negative effects of disclosure to their provider (P < 0.001) compared with cisgender participants. Participants who identified as queer or were questioning their sexual orientation identity reported negative healthcare experiences more frequently than LGB-identified participants (P = 0.001). CONCLUSIONS: Although LGBTQ emerging adults experienced fewer barriers to care than observed in previous studies on LGBTQ adults, the results suggest that queer, questioning, and transgender individuals may face additional healthcare challenges compared with their LGB and cisgender counterparts.

Testosterone replacement therapy among HIV-infected men in the CFAR Network of Integrated Clinical Systems.

OBJECTIVE: The objectives of this study were to determine the rate of testosterone replacement therapy (TRT) initiation, TRT predictors and associated monitoring in HIV-infected men. DESIGN: A multisite cohort study. METHODS: We examined TRT initiation rates and monitoring among adult HIV-infected men in routine care at seven sites in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) from 1996 to 2011. We determined TRT predictors using Cox regression modelling. RESULTS: Of 14 454 men meeting inclusion criteria, TRT was initiated in 1482 (10%) with an initiation rate of 19.7/1000 person-years [95% confidence interval (95% CI) 18.7-20.7]. In the multivariable model, TRT was significantly associated with age at least 35 years, white race, diagnosis of AIDS wasting, hepatitis C coinfection, protease inhibitor based antiretroviral therapy and nadir CD4 cell count of 200 cells/µl or less. Overall, 1886 out of 14 454 (13%) had testosterone deficiency. Among those initiating TRT, 992 out of 1482 (67%) had a pre-TRT serum total testosterone measured, and deficiency [<300 ng/dl (10.4 nmol/l)] was found in 360 out of 1482 (24%). Post-TRT serum total testosterone was measured within 6 months of TRT initiation in 377 out of 1482 (25%) men. CONCLUSION: TRT was common in HIV-infected men, though evidence for pre-TRT testosterone deficiency was lacking in 76%. Endocrine guidelines for post-TRT monitoring were uncommonly followed. Given cardiovascular and other risks associated with TRT, efforts should focus on understanding factors driving these TRT practices in HIV-infected men.

Are HIV-infected men vulnerable to prostate cancer treatment disparities?

BACKGROUND: HIV-infected (HIV(+)) men face cancer treatment disparities that impact outcome. Prostate cancer treatment and treatment appropriateness in HIV(+) men are unknown. METHODS: We used electronic chart review to conduct a retrospective cohort study of 43 HIV(+) cases with prostate cancer and 86 age- and race-matched HIV-uninfected (HIV(-)) controls with prostate cancer, ages 40 to 79 years, from 2001 to 2012. We defined treatment appropriateness using National Comprehensive Cancer Network guidelines and the Charlson comorbidity index (CCI) to estimate life expectancy. RESULTS: Median age was 59.5 years at prostate cancer diagnosis. Median CD4(+) T-cell count was 459.5 cells/mm(3), 95.3% received antiretroviral therapy, and 87.1% were virally suppressed. Radical prostatectomy was the primary treatment for 39.5% of HIV(+) and 71.0% of HIV(-) men (P = 0.004). Only 16.3% of HIV(+) versus 57.0% of HIV(-) men received open radical prostatectomy (P < 0.001). HIV(+) men received more radiotherapy (25.6% vs. 16.3%, P = 0.13). HIV was negatively associated with open radical prostatectomy (OR = 0.03, P = 0.007), adjusting for insurance and CCI. No men were undertreated. Fewer HIV(+) men received appropriate treatment (89.2% vs. 100%, P = 0.003), due to four overtreated HIV(+) men. Excluding AIDS from the CCI still resulted in fewer HIV(+) men receiving appropriate treatment (94.6% vs. 100%, P = 0.03). CONCLUSION: Prostate cancer in HIV(+) men is largely appropriately treated. Under- or overtreatment may occur from difficulties in life expectancy estimation. HIV(+) men may receive more radiotherapy and fewer radical prostatectomies, specifically open radical prostatectomies. IMPACT: Research on HIV/AIDS survival indices and etiologies and outcomes of this prostate cancer treatment disparity in HIV(+) men are needed.

Early suppressive antiretroviral therapy in HIV infection is associated with measurable changes in the corpus callosum.

The purpose of this study was to examine the impact of early suppressive antiretroviral therapy (ART) on brain structure and neurocognitive outcomes. We conducted an observational study of subjects within 1 year of HIV infection. Ten ART-naïve and 10 ART-suppressed individuals were matched for age and infection duration and age-matched to 10 HIV-seronegative controls. Quantitative brain imaging and neurocognitive data were analyzed. Subjects on suppressive ART had diminished corpus callosum structural integrity on macromolecular and microstructural imaging, higher cerebrospinal fluid percent, higher depression scores, and lower functional performance. Early suppressive ART may alter the trajectory of neurological progression of HIV infection, particularly in the corpus callosum.

Accelerated aging and human immunodeficiency virus infection: emerging challenges of growing older in the era of successful antiretroviral therapy.

HIV-infected patients are living longer as a result of potent antiretroviral therapy. Immuno-inflammatory phenomena implicated in the normal aging process, including immune senescence, depreciation of the adaptive immune system, and heightened systemic inflammation are also pathophysiologic sequelae of HIV infection, suggesting HIV infection can potentiate the biological mechanisms of aging. Aging HIV-infected patients manifest many comorbidities at earlier ages, and sometimes with more aggressive phenotypes compared to seronegative counterparts. In this review, we describe relevant biologic changes shared by normal aging and HIV infection and explore the growing spectrum of clinical manifestations associated with the accelerated aging phenotype in HIV-infected individuals.

Persons newly diagnosed with HIV infection are at high risk for depression and poor linkage to care: results from the Steps Study.

Little is known about the prevalence and impact of depression in persons newly diagnosed with HIV infection. The Steps Study is a prospective, observational cohort study of persons newly diagnosed with HIV infection. Participants were administered a battery of instruments, including the CES-D. Linkage to care was defined as attending at least one clinic appointment in each of the first two 90-day intervals following diagnosis. Of 180 participants, 67% screened positive for depression. In multivariate analysis, depression was associated with female sex, income <$25,000, recent substance abuse, baseline poor access to medical care, and low self-efficacy. Fifty-six and sixty-eight percent of depressed and not depressed participants linked to care, respectively. In multivariate analysis, depression was a borderline significant predictor of poor linkage. Depression is very prevalent in persons newly diagnosed with HIV infection. Interventions targeting linkage to care should address depression, substance abuse, and barriers to care.