Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study.

BACKGROUND: Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. METHODS: Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5-10 days post-treatment. RESULTS: Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5-100%). CONCLUSIONS: Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. CLINICAL TRIALS REGISTRATION: NCT02961751.

Despite early Medicaid expansion, decreased durable virologic suppression among publicly insured people with HIV in Washington, DC: a retrospective analysis.

BACKGROUND: Despite widely available access to HIV care in Washington, DC, inequities in HIV outcomes persist. We hypothesized that laboratory monitoring and virologic outcomes would not differ significantly based on insurance type. METHODS: We compared HIV monitoring with outcomes among people with HIV (PWH) with private (commercial payer) versus public (Medicare, Medicaid) insurance receiving care at community and hospital clinics. The DC Cohort follows over 8000 PWH from 14 clinics. We included those ≥18 years old enrolled between 2011 and 2015 with stable insurance. Outcomes included frequency of CD4 count and HIV RNA monitoring (> 2 lab measures/year, > 30 days apart) and durable viral suppression (VS; HIV RNA < 50 copies/mL at last visit and receiving antiretroviral therapy (ART) for ≥12 months). Multivariable logistic regression models examined impact of demographic and clinical factors. RESULTS: Among 3908 PWH, 67.9% were publicly-insured and 58.9% attended community clinics. Compared with privately insured participants, a higher proportion of publicly insured participants had the following characteristics: female sex, Black race, heterosexual, unemployed, and attending community clinics. Despite less lab monitoring, privately-insured PWH had greater durable VS than publicly-insured PWH (ART-naïve: private 70.0% vs public 53.1%, p = 0.03; ART-experienced: private 80.2% vs public 69.4%, p < 0.0001). Privately-insured PWH had greater durable VS than publicly-insured PWH at hospital clinics (AOR = 1.59, 95% CI: 1.20, 2.12; p = 0.001). CONCLUSIONS: Paradoxical differences between HIV monitoring and durable VS exist among publicly and privately-insured PWH in Washington, DC. Programs serving PWH must improve efforts to address barriers creating inequity in HIV outcomes.

Incidence of Venous Thromboembolism in Transgender Women Receiving Oral Estradiol.

INTRODUCTION: One of the most serious known adverse effects of feminizing cross-sex hormone therapy (CSHT) is venous thromboembolism (VTE); however, no study has assessed the incidence of VTE from the hormone therapies used in the United States because previous publications on this topic have originated in Europe. CSHT in the United States typically includes estradiol with the antiandrogen spironolactone, whereas in Europe estradiol is prescribed with the progestin cyproterone acetate. AIM: To estimate the incidence of VTE from the standard feminizing CSHTs used in the United States. METHODS: A retrospective chart review of transgender women who had been prescribed oral estradiol at a District of Columbia community health center was performed. MAIN OUTCOME MEASURE: The primary outcomes of interest were deep vein thrombosis or pulmonary emboli. RESULTS: From January 1, 2008 through March 31, 2016, 676 transgender women received oral estradiol-based CSHT for a total of 1,286 years of hormone treatment and a mean of 1.9 years of CSHT per patient. Only one individual, or 0.15% of the population, sustained a VTE, for an incidence of 7.8 events per 10,000 person-years. CONCLUSION: There was a low incidence of VTE in this population of transgender women receiving oral estradiol.

Person-centred care for older adults living with HIV in sub-Saharan Africa.

More than a fifth of people living with HIV in the US President's Emergency Plan for AIDS Relief-supported programmes are older individuals, defined as aged 50 years and older, yet optimal person-centred models of care for older adults with HIV in sub-Saharan Africa, including screening and treatment for geriatric syndromes and common comorbidities associated with ageing, remain undefined. This Position Paper explores the disproportionate burden of comorbidities and geriatric syndromes faced by older adults with HIV, with a special focus on women. We seek to motivate global interest in improving quality of life for older people with HIV by presenting available research and identifying research gaps for common geriatric syndromes, including frailty and cognitive decline, and multimorbidity among older people with HIV in sub-Saharan Africa. We share two successful models of holistic care for older people with HIV that are ongoing in Zimbabwe and Kenya. Lastly, we provide policy, research, and implementation considerations to best serve this growing population.

Integrating global HIV services with primary health care: a key step in sustainable HIV epidemic control.

Ending the HIV epidemic relies in part on integrating stand-alone HIV programming with primary health-care platforms to improve population-level health and ensure sustainability. Integration of HIV and primary health care services in sub-Saharan Africa improves both outcomes. Existing models support both integrating primary health care services into existing HIV services, and incorporating HIV services into primary health care platforms, with optimal programming based on local contexts and local epidemic factors. Person-centred differentiated service delivery, community-based interventions, and a well supported health workforce form the backbone of successful integration. Strategic financing to optimise HIV and primary health care integration requires well-coordinated partnerships with host governments, private sector companies, multilateral stakeholders, development banks, and non-government organisations. Programme success will require increased flexibility of international donors' implementation guidance as well as involvement of local communities and civil society organisations. As we seek to end the HIV epidemic by 2030 amidst a constrained global economic climate, integration of HIV programming with primary health care offers an avenue of opportunity and hope.

Lipid profiles and hypertriglyceridemia among transgender and gender diverse adults on gender-affirming hormone therapy.

BACKGROUND: The effects of gender-affirming hormone therapy on lipid profiles among transgender adults have been inconsistent and incompletely characterized. OBJECTIVE: To longitudinally assess changes to lipid profiles following hormone therapy and to establish prevalence rates of hyperlipidemia/low HDL-cholesterol. METHODS: This longitudinal study followed lipid profiles of 366 transgender and gender-diverse adult patients (170 transfeminine and 196 transmasculine; mean age, 28 years) in Washington DC USA. Lipid profiles were measured at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of hormone therapy. RESULTS: Within 2-10 months of starting gender-affirming hormone therapy, mean levels of HDL-cholesterol decreased by 16% in transmasculine individuals and increased by 11% in transfeminine individuals. Over the study, mean triglyceride levels increased by 26-37% in the transmasculine group. Over the study, the prevalence of moderate hypertriglyceridemia (175-499 mg/dL) ranged from 11 to 32% in the transfeminine group and 6-19% in the transmasculine group. Severe hypertriglyceridemia (≥500 mg/dL) was only observed in one individual. On hormone therapy, 24-30% of the transfeminine group had a HDL-cholesterol < 50 mg/dL and 16-24% of the transmasculine group had a HDL-cholesterol < 40 mg/dL. LDL-cholesterol levels ≥160 mg/dL were rare among both groups. CONCLUSIONS: In a gender-diverse population on hormone therapy, low HDL-cholesterol and moderate hypertriglyceridemia were relatively common. HDL-cholesterol decreased with testosterone therapy and increased with a combination of oral estrogen and spironolactone. Testosterone use was associated with an increase in triglycerides. Our data support the recommendation to routinely monitor lipid profiles in gender-diverse patients on GAHT.

Person-centred, integrated non-communicable disease and HIV decentralized drug distribution in Eswatini and South Africa: outcomes and challenges.

INTRODUCTION: Non-communicable diseases (NCDs) are highly prevalent in people living with HIV above 50 years of age and account for increasing mortality. There is little published evidence supporting person-centred, integrated models of HIV care, hypertension and diabetes treatment in southern Africa, and no data demonstrating mortality reduction. Where clinical visits for NCDs and HIV cannot be combined, integrated medication delivery presents an opportunity to streamline care and reduce patient costs. We present experiences of integrated HIV and NCD medication delivery in Eswatini and South Africa, focusing on programme successes and implementation challenges. Programmatic data from Eswatini's Community Health Commodities Distribution (CHCD) from April 2020 to December 2021 and South Africa's Central Chronic Medicines Dispensing and Distribution (CCMDD) from January 2016 to December 2021 were provided by programme managers and are summarized here. DISCUSSION: Launched in 2020, Eswatini's CHCD provides over 28,000 people with and without HIV with integrated services, including HIV testing, CD4 cell count testing, antiretroviral therapy refills, viral load monitoring and pre-exposure prophylaxis alongside NCD services, including blood pressure and glucose monitoring and hypertension and diabetes medication refills.  Communities designate neighbourhood care points and central gathering places for person-centred medication dispensing.  This programme reported fewer missed medication refill appointments among clients in community settings compared to facility-based settings. South Africa's CCMDD utilizes decentralized drug distribution to provide medications for over 2.9 million people, including those living with HIV, hypertension and diabetes.  CCMDD incorporates community-based pickup points, facility "fast lanes" and adherence clubs with public sector health facilities and private sector medication collection units.  There are no out-of-pocket payments for medications or testing commodities.  Wait-times for medication refills are lower at CCMDD sites than facility-based sites.  Innovations to reduce stigma include uniformly labelled medication packages for NCD and HIV medications. CONCLUSIONS: Eswatini and South Africa demonstrate person-centred models for HIV and NCD integration through decentralized drug distribution. This approach adapts medication delivery to serve individual needs and decongest centralized health facilities while efficiently delivering NCD care.  To bolster programme uptake, additional reporting of integrated decentralized drug distribution models should include HIV and NCD outcomes and mortality trends.

Blood Pressure Effects of Gender-Affirming Hormone Therapy in Transgender and Gender-Diverse Adults.

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HIV/HCV therapy with ledipasvir/sofosbuvir after randomized switch to emtricitabine-tenofovir alafenamide-based single-tablet regimens.

INTRODUCTION: Guidelines advocate the treatment of HCV in all HIV/HCV co-infected individuals. The aim of this randomized, open-label study (ClinicalTrials.gov identifier: NCT02707601; https://clinicaltrials.gov/ct2/show/NCT02707601) was to evaluate the safety/efficacy of ledipasvir/sofosbuvir (LDV/SOF) co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or rilpivirine/F/TAF (R/F/TAF) in HIV-1/HCV co-infected participants. METHODS: Participants with HIV-1 RNA <50 copies/mL and chronic HCV-genotype (GT) 1 (HCV treatment-naïve ± compensated cirrhosis or HCV treatment-experienced non-cirrhotic) were randomized 1:1 to switch to E/C/F/TAF or R/F/TAF. If HIV suppression was maintained at Week 8, participants received 12 weeks of LDV/SOF. The primary endpoint was sustained HCV virologic response 12 weeks after LDV/SOF completion (SVR12). RESULTS: Of 150 participants, 148 received ≥1 dose of HIV study drug and 144 received LDV/SOF (72 in each F/TAF group; 83% GT1a, 94% HCV treatment-naïve, 12% cirrhotic). Overall, SVR12 was 97% (95% confidence interval: 93-99%). Black race did not affect SVR12. Of four participants not achieving SVR12, one had HCV relapse, one had HCV virologic non-response due to non-adherence, and two missed the post-HCV Week 12 visit. Of 148 participants, 96% receiving E/C/F/TAF and 95% receiving R/F/TAF maintained HIV suppression at Week 24; no HIV resistance was detected. No participant discontinued LDV/SOF or E/C/F/TAF due to adverse events; one participant discontinued R/F/TAF due to worsening of pre-existing hypercholesterolemia. Renal toxicity was not observed in either F/TAF regimen during LDV/SOF co-administration. In conclusion, high rates of HCV SVR12 and maintenance of HIV suppression were achieved with LDV/SOF and F/TAF-based regimens. CONCLUSION: This study supports LDV/SOF co-administered with an F/TAF-based regimen in HIV-1/HCV-GT1 co-infected patients.

Transgender and Nontrans Patients Do Not Receive Statistically Different Quality Primary Care at Whitman-Walker Health, 2008-2016.

Purpose: Washington, DC, has the highest prevalence of transgender persons in the United States at 2.8%. Transgender persons in DC have lower income, less stable housing, and more HIV infection than nontrans persons. Data are scarce regarding primary care quality among trans persons. We provide a detailed analysis of transgender patients at Whitman-Walker Health, an HIV- and LGBT-focused community health center. Methods: We performed a retrospective electronic medical record review of transgender patients ≥18 years of age from 2008 to 2016, evaluating demographic factors, HIV status, gender-affirming care, and primary care quality indicators. Results: Of 20,097 patients, 1822 (9.0%) self-identify as transgender (62.9% trans female and 37.2% trans male), and 18,275 were nontransgender. Transgender patients are more likely to be young, white, HIV negative, and reside outside Washington, DC, than nontrans patients. Transgender patients are more likely to engage in primary care and have a similar likelihood of mammogram and colonoscopy screening than nontrans patients. Trans males are more likely to be privately insured, have lower rates of HIV testing than nontrans patients, and have higher rates of cervical Pap smears than cis females. Trans females have a high prevalence of HIV infection (26.6%). Conclusion: This is the largest single-center U.S. transgender cohort to date. Over a quarter of trans females are HIV positive, consistent with a national prevalence of 27.7%. Transgender and nontrans patients do not receive statistically different quality of primary care. Trans patients' high engagement in primary care may result from providing hormone therapy and primary care within a single provider visit.

Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial.

BACKGROUND: Cabotegravir (GSK1265744) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity and a long half-life when administered by injection that prevented simian-HIV infection upon repeat intrarectal challenge in male macaques. We aimed to assess the safety, tolerability, and pharmacokinetics of long-acting cabotegravir injections in healthy men not at high risk of HIV-1 infection. METHODS: We did this multicentre, double-blind, randomised, placebo-controlled, phase 2a trial at ten sites in the USA. Healthy men (aged 18-65 years) deemed not at high risk of acquiring HIV-1 at screening were randomly assigned (5:1), via computer-generated central randomisation schedules, to receive cabotegravir or placebo. Participants received oral cabotegravir 30 mg tablets or matching placebo once daily during a 4 week oral lead-in phase, followed by a 1 week washout period and, after safety assessment, three intramuscular injections of long-acting cabotegravir 800 mg or saline placebo at 12 week intervals. Study site staff and participants were masked to treatment assignment from enrolment through week 41 (time of the last injection). The primary endpoint was safety and tolerability from the first injection (week 5) to 12 weeks after the last injection. We did analysis in the safety population, defined as all individuals enrolled in the study who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov identifier, NCT02076178. FINDINGS: Between March 27, 2014, and Feb 23, 2016, we randomly assigned 127 participants to receive cabotegravir (n=106) or placebo (n=21); 126 (99%) participants comprised the safety population. Most participants were men who have sex with men (MSM; n=106 [83%]) and white (n=71 [56%]). 87 (82%) participants in the cabotegravir group and 20 (95%) participants in the placebo group completed the injection phase. Adverse events (n=7 [7%]) and injection intolerability (n=4 [4%]) were the main reasons for withdrawal in the cabotegravir group. The frequency of grade 2 or higher adverse events was higher in participants in the long-acting cabotegravir group (n=75 [80%]) than in those in the placebo group (n=10 [48%]; p=0·0049), mostly due to injection-site pain (n=55 [59%]). No significant differences were noted in concomitant medications, laboratory abnormalities, electrocardiogram, and vital sign assessments. Geometric mean trough plasma concentrations were 0·302 µg/mL (95% CI 0·237-0·385), 0·331 µg/mL (0·253-0·435), and 0·387 µg/mL (0·296-0·505) for injections one, two, and three, respectively, indicating lower than predicted exposure. The geometric mean apparent terminal phase half-life estimated after the third injection was 40 days. Two (2%) MSM acquired HIV-1 infection, one in the placebo group during the injection phase and one in the cabotegravir group 24 weeks after the final injection when cabotegravir exposure was well below the protein-binding-adjusted 90% inhibitory concentration. INTERPRETATION: Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile. Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated. Our findings support further investigation of long-acting injectable cabotegravir as an alternative to orally administered pre-exposure prophylaxis regimens. FUNDING: ViiV Healthcare.

HIV-associated intracranial aneurysmal vasculopathy in adults.

Diffuse fusiform intracranial aneurysms have been reported in children with human immunodeficiency virus (HIV) for over 2 decades, but have only recently been reported in adults with HIV. Although these aneurysms have important clinical implications, their etiology and optimal therapy are unknown. We present a systematic review of diffuse intracranial fusiform aneurysmal vasculopathy in patients who are HIV-positive. We conducted a comprehensive literature search for relevant case reports and reviews published before February 2009. Patients were included if they had HIV infection and radiographic imaging consistent with fusiform aneurysmal vasculopathy. We identify 11 published adult cases of intracranial fusiform aneurysmal vasculopathy and describe 1 unpublished case from our own institution. Available data regarding clinical presentation, characteristic imaging findings, and treatment of this complex syndrome are reviewed. Adults with HIV-associated intracranial aneurysmal vasculopathy typically are significantly immunosuppressed and present with gross neurologic dysfunction. Characteristic radiographic findings include diffuse cerebral fusiform aneurysms with hemorrhage or infarct. Treatment of any active infection followed by the initiation of antiretroviral therapy and corticosteroids may be a reasonable approach in this complex syndrome.

Hepatitis C viral kinetics during treatment with peg IFN-alpha-2b in HIV/HCV coinfected patients as a function of baseline CD4+ T-cell counts.

BACKGROUND: HIV/hepatitis C virus (HCV) coinfected patients are known to have lower sustained viral response (SVR) rates than HCV monoinfected patients. However, the role of CD4+ T-cell counts on viral kinetics and outcome is not fully understood. METHODS: HCV RNA kinetics (bDNA v3, lower limit of detection [LD] = 615 IU/mL) was analyzed in 32 HIV/HCV coinfected persons treated with Pegylated-interferon-alpha2b (1.5 microg/kg weekly) and ribavirin (1-1.2 g daily) for 48 weeks and compared with results obtained from 12 HCV monoinfected patients treated with the same regimen. RESULTS: Baseline CD4+ T-cell counts > or =450 cells/mm3 were significantly (P < 0.002) associated with SVR in coinfected genotype 1 patients. First phase decline was significantly lower among patients with low as compared with high CD4 counts (P < 0.03) and among coinfected compared with monoinfected patients (P < 0.002). Second phase decline slope showed a similar trend for coinfected patients. CONCLUSIONS: Low baseline CD4+ T-cell count is associated with slower HCV viral kinetics and worse response to treatment among HIV coinfected patients, suggesting HCV treatment response depends on immune status. HCV genotype 1 coinfected patients have slower first phase viral kinetics than HCV monoinfected patients. First phase viral decline (>1.0 log) and second phase viral decline slope (>0.3 log/wk) are excellent predictors of SVR for coinfected patients.

Cultural competence among staff nurses who participated in a family-centered geriatric care program.

The purpose of this training program was to prepare nursing staff in family-centered geriatric care that emphasizes providing culturally competent care to hospitalized elders at two major tertiary hospitals in New York. This research report corresponds to the first phase of a 3-year project. In this research project, a descriptive exploratory design was used to identify the levels of cultural awareness and cultural competence of nursing staff who participated in a family-centered geriatric care training program.