Effective use of pre-exposure prophylaxis (PrEP) Among stimulant users with multiple condomless sex partners: a longitudinal study of men who have sex with men in Los Angeles.

PrEP's potential benefit for men who have sex with men (MSM) who use stimulants may be limited by adherence or prescriber willingness to recommend PrEP due to concerns of non-compliance. Using data from PATH-PrEP, a 48-week study evaluating PrEP for MSM in Los Angeles, we modeled an interaction between stimulant use and condomless sex with multiple partners (CAS-MP) on prevention-effective dried blood spot tenofovir-diphosphate concentrations. At week 4, participants reporting stimulant use and CAS-MP had a decreased odds of prevention-effective adherence compared to non-stimulant use and non-CAS-MP (AOR 0.15, 95% CI 0.04-0.57). From week 4-48, participants reporting stimulant use and CAS-MP had increased odds of prevention-effective adherence (AOR 1.06 per week, 95%CI 1.01-1.12). Participants reporting CAS-MP without stimulant use had no significant change in prevention-effective adherence (AOR 0.99 per week, 95%CI 0.96-1.02). Stimulant use moderated the association of CAS-MP on prevention-effective PrEP adherence over time.

Proprotein convertase subtisilin/kexin 9 levels decline with hepatitis C virus therapy in people with HIV/hepatitis C virus and correlate with inflammation.

BACKGROUND: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9. DESIGN: A prospective, observational cohort study. METHODS: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations. RESULTS: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284 ng/ml, P  = 0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3 weeks after end of therapy [EOT]) and posttreatment 2 (median 43.5 weeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5 ng/ml ( P  = 0.003) and -55.6 ng/ml ( P  = 0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 ( r  = 0.64, P  = 0.002; r  = 0.58, P  = 0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52 weeks. CONCLUSION: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis.

HIV testing practices among black primary care physicians in the United States.

BACKGROUND: The Centers for Disease Control and Prevention recommends routine HIV testing in all healthcare settings, but it is unclear how consistently physicians adopt the recommendation. Making the most of each interaction between black physicians and their patients is extremely important to address the HIV health disparities that disproportionately afflict the black community. The goal of this survey-based study was to evaluate the perceptions and practices of black, primary care physicians regarding HIV testing. METHODS: A physician survey was administered at the 2010 National Medical Association Annual Convention, via online physician panels, and by email. Physician eligibility criteria: black race; practicing at least 1 year in the US; practice comprised of at least 60% adults and 20% black patients. Contingency tables and ordinary least squares regression were used for comparisons and statistical analyses. A Chi-square test compared percentages of physicians who gave a particular response and a t-test compared the means of values provided by physicians. RESULTS: Physicians over-estimated HIV prevalence and believed that HIV is a crisis in the black community, yet reported that only 34% of patients were HIV tested in the past year. Physicians reported that 67% of those patients tested did so due to a physician recommendation. Physicians who were younger, female, obstetricians/gynecologists, and had a higher proportion of black, low-socioeconomic status, and Medicaid patients reported higher testing rates. Most testing was risk-based rather than routine, and three of the five most commonly reported barriers to testing were related to disease stigma and perceived value judgments. Physicians reported that in-office patient informational materials, increased media attention, additional education and training on HIV testing, government mandates requiring routine testing, and accurate pre-packed tests would most help them test more frequently for HIV. CONCLUSIONS: In this sample of black, primary care physicians, HIV testing practices differed according to physician characteristics and practice demographics, and overall reported testing rates were low. More physician education and training around testing guidelines is needed to enable more routine testing, treatment, and long-term management of patients with HIV.

Barriers to Testing for Sexually Transmitted Infections among HIV-Serodiscordant Couples: The Influence of Discrimination.

Objectives: African Americans face challenges in accessing services for sexually transmitted infections (STIs). From 2012-2016, the EBAN II intervention was funded by the NIH to test the effectiveness of implementing a culturally congruent, evidence-based HIV/AIDS prevention program in Los Angeles and Oakland, California. This study examined the impact of personal characteristics and experiences of discrimination on the likelihood of being tested for STIs. Methods: Participants (N=91) completed a baseline survey. Descriptive statistics were used to test for differences between those who did and did not obtain STI testing. Factors included HIV serostatus, sociodemographic variables, STI history, the presence of outside partners, and discrimination experiences. Multiple logistic regressions were conducted for men and women separately. Results: Participants with no recent experiences of discrimination were more than 3 (3.4) times more likely to obtain a baseline STI test than those who reported discrimination experiences. HIV-positive women with no recent experiences of discrimination were 11 times more likely than those with reports of recent discrimination to obtain STI tests. Conclusions: It is often women who are the gatekeepers for health seeking in families and the same may be for these couples. Experiences of discrimination may impede STI testing, and heighten several health risks, particularly among HIV-positive African American women in HIV-serodiscordant relationships. Addressing the impact of discrimination experiences may be important for STI prevention and treatment efforts in interventions promoting health care utilization.

PrEP Nonadherence, White Coat Dosing, and HIV Risk Among a Cohort of MSM.

Among a cohort of men who have sex with men in a pre-exposure prophylaxis (PrEP) adherence trial, syphilis requiring treatment was associated with white coat dosing (increased PrEP adherence immediately preceding study visits) when compared with participants with optimal drug concentrations. The findings highlight the need for identifying and reducing barriers to PrEP adherence.

Results from the post-exposure prophylaxis pilot program (P-QUAD) demonstration project in Los Angeles County.

Post-exposure prophylaxis (PEP) is a promising but under-utilized strategy for HIV prevention in high-risk populations. Between March 2010 and June 2011, two community-based clinics in Los Angeles County provided PEP in a pilot program to 267 unique individuals. Courses were primarily dispensed to men who have sex with men (84%) and consisted overwhelmingly of a three-drug antiretroviral therapy regimen containing two nucleoside reverse transcriptase inhibitors and either an integrase inhibitor (raltegravir) or a boosted protease inhibitor (lopinavir/ritonavir). Approximately 64% of all PEP courses were followed for at least 12 weeks, and seven individuals seroconverted. Of the seven seroconversions, six had subsequent re-exposure. The low rate of PEP failure calls for expanded funding for PEP in other jurisdictions.

Reaching lost-to-care populations.

Identification of patients who are at high risk for human immunodeficiency virus (HIV) infection can lead to reduced frequencies of high-risk behaviors, provision of timely care for infected individuals, and decreased transmission of HIV. The HIV-associated outreach programs at the OASIS Clinic of the King-Harbor/Drew University complex (Los Angeles, CA) has 3 components: a traditional partner-notification (i.e., contact-tracing) component, a focused-intervention component through which clients are given incentives to bring in persons they feel are at high risk for HIV infection, and an outreach component targeting hard-to-reach populations. These interventions are highly effective in identifying individuals early during the course of their disease, when initiation of antiretroviral therapy is most effective. The partner-services program at the OASIS Clinic has been particularly useful in identifying partners of HIV-positive women, whereas the focused-intervention program is most useful for identifying gay men who are unaware of their positive HIV serostatus. Successful targeted outreach programs can identify many individuals who would not otherwise be aware of their HIV infection, but the programs also require more clinicians to manage these patients.

Plasma Tenofovir Levels to Support Adherence to TDF/FTC Preexposure Prophylaxis for HIV Prevention in MSM in Los Angeles, California.

BACKGROUND: Tenofovir disoproxil fumarate/emtricitabine preexposure prophylaxis (PrEP) is effective against HIV acquisition when taken as prescribed. Strategies that identify and intervene with those challenged by adherence to daily medication are needed. SETTING: PATH-PrEP was an open-label single-arm interventional cohort study conducted at 2 community-based clinical sites in Los Angeles, CA. METHODS: We enrolled self-identified men who have sex with men and transgender women ≥18 years of age at an elevated risk of HIV acquisition. Participants received a postexposure prophylaxis (PEP)-based or PrEP-based HIV prevention package for at least 48 weeks. Plasma tenofovir levels from each PrEP visit assessed as below the limit of quantitation (<10 ng/mL) triggered increased adherence support. RESULTS: Three hundred one participants enrolled. Forty-eight-week retention in the PrEP cohort was 75.1%. Biomarker evidence of PrEP adherence consistent with ≥4 doses per week at weeks 4, 12, 24, 36, and 48 was found in 83.1%, 83.4%, 75.7%, 71.6%, and 65.5% of participants, respectively; younger and African American participants were less likely to have protective drug levels. Most of those with suboptimal adherence had adherence improvement after brief intervention. One seroconversion occurred in a participant who discontinued PrEP. Nearly half (46.4%) of participants were diagnosed with at least 1 incident sexually transmitted infection during 48 weeks of study follow-up. CONCLUSIONS AND RELEVANCE: PrEP was acceptable and well tolerated in a diverse population of men who have sex with men in Los Angeles. A brief intervention triggered from biomarkers of poor adherence was associated with improved adherence. Drug level monitoring has the potential to allow targeting of additional adherence support to those struggling with daily tablet adherence.

Optimizing treatment for African Americans and Latinos with HIV/AIDS.

HIV/AIDS is a disease that has a disproportionate negative impact on the African-American and Latino communities when compared with the general population. African Americans account for more than 50% of new AIDS cases, though they comprise only 12% of the general population. More than one-third of AIDS-related deaths in the United States have been among African Americans. Many factors contribute to the HIV/AIDS healthcare disparities seen in the African-American and Latino communities. These factors include medical issues (such as resistance to antiretroviral therapy, toxicities of medications and hepatitis-C coinfection) and social factors (such as a lack of faith in the healthcare system, cultural circumstances and poor access to healthcare services). Healthcare providers can take steps to improve HIV care for African Americans and Latinos. Distrust of the medical establishment can be addressed by increasing the number of culturally sensitive healthcare providers. Communication is the first step toward establishing the trust of patients and minimizing the devastating effects of perceived institutional bias that may lead many HIV patients to be diagnosed late in the course of the disease. Medical and cultural issues faced by African Americans and Latinos should also be addressed in treatment guidelines. When healthcare providers take steps to overcome the medical and cultural issues facing African Americans and Latinos, HIV patients will have access to more effective disease management.

Nevirapine plus efavirenz plus didanosine: a simple, safe, and effective once-daily regimen for patients with HIV infection.

Conventional highly active antiretroviral therapy (HAART) regimens used to treat human immunodeficiency virus (HIV) infection typically use nucleoside reverse transcriptase inhibitors (NRTIs) and either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Because PI-based regimens are associated with significant long-term toxicity and adherence difficulty, there is a need for novel regimens that maximize combination treatment options. This 12-month, observational, cohort study evaluated the efficacy, safety, and tolerability of a novel three-drug HAART regimen. Drug treatment consisted of nevirapine (NVP), efavirenz (EFV), and didanosine (ddl). Twenty-six treatment-naive and -experienced HIV-1+ men and women were included in the study. Assessment consisted of CD4+ cell count, plasma HIV-1 RNA load, and adverse effects of study medications. After one year of therapy, 11/12 treatment-naive subjects (92%) and 8/9 treatment-experienced subjects (89%) had viral loads < 400 copies/mL. Both groups also had an excellent immune response. At one year, there was a mean increase of 438 CD4+ cells/mm3 among treatment-naive subjects and 367 cells/mm3 among treatment-experienced subjects. Treatment-limiting adverse effects occurred in 3/15 treatment-naive (20%) and 2/11 treatment-experienced (18%) subjects. These preliminary data suggest that the combination of NVP, EFV, and ddl is simple, safe, and effective.

African Americans and HIV/AIDS: cultural concerns.

AIDS is a disease that has had a disproportionate effect on African Americans. While there has been significant progress in the treatment of people with HIV infection, there are obstacles to the optimal treatment of African Americans, such as distrust of the medical system, cultural differences between patients and providers, and institutional racism. To optimize treatment of African Americans with HIV/AIDS, health care providers must learn more about cultural issues that impact treatment. The goals of treatment for African Americans with HIV infection are the same as those for all patients: maintain durable suppression of HIV replication, prevent resistance, support optimal immune system function, extend AIDS-free survival time, maximize adherence to antiretroviral regimens, and improve quality of life.

Brief sexual histories and routine HIV/STD testing by medical providers.

Clinicians who routinely take patient sexual histories have the opportunity to assess patient risk for sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV), and make appropriate recommendations for routine HIV/STD screenings. However, less than 40% of providers conduct sexual histories with patients, and many do not receive formal sexual history training in school. After partnering with a national professional organization of physicians, we trained 26 (US and US territory-based) practicing physicians (58% female; median age=48 years) regarding sexual history taking using both in-person and webinar methods. Trainings occurred during either a 6-h onsite or 2-h webinar session. We evaluated their post-training experiences integrating sexual histories during routine medical visits. We assessed use of sexual histories and routine HIV/STD screenings. All participating physicians reported improved sexual history taking and increases in documented sexual histories and routine HIV/STD screenings. Four themes emerged from the qualitative evaluations: (1) the need for more sexual history training; (2) the importance of providing a gender-neutral sexual history tool; (3) the existence of barriers to routine sexual histories/testing; and (4) unintended benefits for providers who were conducting routine sexual histories. These findings were used to develop a brief, gender-neutral sexual history tool for clinical use. This pilot evaluation demonstrates that providers were willing to utilize a sexual history tool in clinical practice in support of HIV/STD prevention efforts.