Katerina Christopoulos’s research while affiliated with University of California, San Francisco and other places

Background Point-of-care HIV viral load testing may enhance patient care and improve HIV health services. We aimed to evaluate the feasibility and acceptability of implementing such testing in a high-volume community sexual health clinic in the United States. Methods We conducted a cross-sectional, mixed-methods study. Remnant venipuncture specimens from clients undergoing HIV and other sexual health screenings were analyzed using the Xpert® HIV-1 Viral Load assay. Results were compared to COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test. Clinical staff observations, study meeting notes, and two semi-structured in-depth interviews with clinical staff were used to understand perspectives on incorporating this testing into clinical practice. Results We analyzed 113 samples from 111 clients. The Xpert assay showed excellent agreement with COBAS, with no clinically significant difference in viral load measurements. Clinical staff found Xpert testing acceptable, based on its ability to provide rapid, accurate test results and potential for bridging patient care gaps. Respondents noted that this testing would be particularly beneficial for individuals in whom barriers to care engagement may complicate follow-up. Challenges in implementation included machine errors as well as concerns related to staff workload, testing logistics, and the need for comprehensive equipment training. Conclusions This study represents the first effort in the United States to describe the feasibility of HIV viral load point-of-care testing in routine care. While the Xpert demonstrated comparable results to standard-of-care testing and staff found it acceptable, further work is needed to develop the workflow and implementation strategies that would enable real-time use and improved patient care. Clinical trial Not applicable.

Background People with HIV (PWH) have benefited greatly from antiretroviral therapy, but face additional challenges from age-related comorbid conditions, particularly cardiovascular disease including venous thromboembolism (VTE). Little is known about the effect of HIV viremia and immunodeficiency on VTE risk in this population. Methods We assessed incident, centrally adjudicated VTE among 21,507 PWH in care between 1/2009–12/2019 within the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. We examined the association of three measures of HIV viral load (VL: baseline, current, cumulative) and current CD4 count with VTE. Cumulative VL (copy-days of viremia) was estimated with a time-weighted sum using the trapezoidal rule. We modeled the association between VL and VTE using Cox proportional hazards models (marginal structural Cox models for cumulative), adjusted for demographic and clinical characteristics. We compared the 75 th percentile of the VL distribution with the 25 th percentile using the hazard function from the model for all PWH with a VTE and those with a pulmonary embolism (PE). Results During a median of 4.8 years of follow-up, 424 PWH developed VTE. In adjusted analyses, higher cumulative VL (75 th percentile vs. 25 th percentile), the strongest VL predictor, was associated with a 1.45-fold higher risk of VTE (95%CI:1.22–1.72). Low CD4 cell count <100 cells/mm ³ was associated with higher VTE risk (HR: 4.03, 95%CI: 2.76–5.89) as compared to ≥500 cells/mm ³ . Findings were similar for PWH who had a pulmonary embolism (n = 189). Conclusions Reducing HIV VL and maintaining CD4 cell count may help mitigate VTE risk in PWH.

Introduction Perspectives on long‐acting injectable cabotegravir/rilpivirine (CAB/RPV‐LA) from HIV health disparity populations are under‐represented in current literature yet crucial to optimize delivery. Methods Between August 2022 and May 2023, we conducted in‐depth interviews with people with HIV (PWH) at four HIV clinics in Atlanta, Chicago and San Francisco. Eligibility criteria were current CAB/RPV‐LA use with receipt of ≥3 injections or CAB/RPV‐LA discontinuation. We purposefully sampled for PWH who initiated with viraemia (plasma HIV RNA >50 copies/ml) due to adherence challenges, discontinuers, and cis and trans women. Interviews were coded and analysed using thematic methods grounded in descriptive phenomenology. Clinical data were abstracted from the medical record. Results The sample (San Francisco n = 25, Atlanta n = 20, Chicago n = 14 for total n = 59, median number of injections = 6) consisted of 48 PWH using CAB/RPV‐LA and 11 who had discontinued. The median age was 50 (range 25–73) and 40 (68%) identified as racial/ethnic minorities, 19 (32%) cis or trans women, 16 (29%) were experiencing homelessness/unstable housing, 12 (20%) had recently used methamphetamine or opioids and 11 (19%) initiated with viraemia. All participants except one (who discontinued) had evidence of viral suppression at interview. Typical benefits of CAB/RPV‐LA included increased convenience, privacy and freedom from being reminded of HIV and reduced anxiety about forgetting pills. However, PWH who became virally suppressed through CAB/RPV‐LA use also experienced an amelioration of feelings of shame and negative self‐worth related to oral adherence challenges. Regardless of baseline viral suppression status, successful use of CAB/RPV‐LA amplified positive provider/clinic relationships, and CAB/RPV‐LA was often viewed as less “work” than oral antiretroviral therapy, which created space to attend to other aspects of health and wellness. For some participants, CAB/RPV‐LA remained “work,” particularly with regard to injection site pain and visit frequency. At times, these burdens outweighed the aforementioned benefits, resulting in discontinuation. Conclusions CAB/RPV‐LA offers a range of logistical, psychosocial and care engagement benefits, which are experienced maximally by PWH initiating with viraemia due to adherence challenges; however, benefits do not always outweigh treatment burdens and can result in discontinuation. Our findings on rationales for persistence versus discontinuation can inform both initial and follow‐up patient counselling.

Purpose of review Recent changes in US Department of Health and Human Services and International AIDS Society USA guidelines now endorse use of long-acting injectable cabotegravir and rilpivirine (LA-CAB/RPV) in people with HIV (PWH) who have adherence challenges, including those with viremia. We sought to summarize clinical trial and real-world study data on outcomes and implementation strategies, highlight key unanswered questions, and provide recommendations for best practices. Recent findings Studies of LA-CAB/RPV in PWH with adherence challenges demonstrate excellent virologic outcomes, although the rate of virologic failure is higher than that in registrational trials conducted in PWH with stable viral suppression. However, viral suppression is attainable on alternate antiretroviral regimen, including those that employ lenacapavir, another long-acting injectable antiretroviral drug, even after virologic failure on LA-CAB/RPV. Successful implementation strategies for long-acting programs include centralized multidisciplinary clinic teams (ideally with pharmacist/pharmacy technician involvement), small incentives to promote patient retention on injections, allowing for drop-in injections, outreach after late injections, and partnerships with home nursing, street medicine, and harm reduction sites. Summary Creating programs that can support PWH with adherence challenges, their providers, and their clinics to use LA-CAB/RPV in service of sustained viral suppression is an urgent priority, particularly for PWH with CD4 ⁺ cell count <200 cells/mm ³ .

Background Doxycycline post-exposure prophylaxis (doxy-PEP) reduces chlamydia, gonorrhea, and syphilis infections among men who have sex with men (MSM) and transwomen (TW). Perspectives of health care providers (HCPs) regarding doxy-PEP can inform implementation efforts. Methods From August 2022 to January 2023, HCPs were recruited from 13 cities with high sexually transmitted infection (STI) rates for semi-structured, in-depth interviews about their awareness of and attitudes towards doxy-PEP for STI prevention. HCPs were purposively sampled to include people with experience prescribing PrEP and provision of care to MSM. Interviews were conducted virtually via Zoom. Transcripts and debrief reports were analyzed using a directed content analysis approach to explore knowledge, attitudes, and beliefs about doxy-PEP. Results Among 30 HCPs, almost half (47%) were between 31-40 years of age, 53% identified as male, and 47% reported their sexual orientation as gay or queer. Half (53%) of participants practiced in the South, 43% had >100 MSM in their clinic panel, and 17% had previously prescribed doxy-PEP. We identified four overarching themes: 1) HCPs expressed positive attitudes towards doxy-PEP; 2) antimicrobial resistance concerns limit enthusiasm for some HCPs; 3) additional data about the long-term safety of doxy-PEP would improve their confidence; and 4) development of guidelines would facilitate the prescription of doxy-PEP, including eligibility, dosing instructions, and treatment management. Conclusion HCPs were motivated to prescribe doxy-PEP with almost 20% already having prescribed it. Guidelines and data about long-term safety, especially antimicrobial resistance, would facilitate introduction of doxy-PEP into clinical practice.

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010–2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1–3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4–26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used.

Introduction Since its global reemergence in 2022, monkeypox (mpox) has demonstrated increased incidence and severity among people with human immunodeficiency virus (HIV [PWH]). Predictors of mpox diagnosis, vaccination, and outcomes among PWH are limited. Methods We included PWH with primary care visits after 1 January 2022 at 9 US sites participating in the Centers for AIDS Research Network of Integrated Clinic Systems Network. We identified mpox diagnosed between 1 June 2022 and 31 May 2023, through a combination of polymerase chain reaction result, diagnosis code, and/or tecovirimat receipt. We examined validated clinical diagnoses, laboratory results, vaccine data, and patient reported outcomes. We evaluated relative risks (RR) of mpox diagnosis, hospitalization, tecovirimat treatment, and vaccine receipt. Findings Among 19 777 PWH in care, 413 mpox cases (all male sex at birth) occurred (2.2 cases/100 person-years). Age <40 years, geographic region, Hispanic/Latine ethnicity, lack of antiretroviral therapy, detectable HIV viral load, and recent bacterial sexually transmitted infection predicted mpox diagnosis. PWH with CD4 200–349 cells/mm3 were most likely to be hospitalized (adjusted RR, 3.20; 95% confidence interval: 1.44–7.09) compared to CD4 ≥500, but half as likely as those with CD4 <200 to receive tecovirimat. Overall, smallpox/mpox vaccine effectiveness of ≥1 vaccine was 71% (adjusted RR, 0.29; 95% confidence interval: .14–.47) at preventing mpox, and 86% or better with CD4 ≥350 or HIV viral suppression. Non-Hispanic Black PWH were less likely to be vaccinated than other racial/ethnic identities. Interpretation PWH not on antiretroviral therapy or with unsuppressed HIV were more likely to be diagnosed with, and hospitalized for, mpox. Mpox/smallpox vaccine effectiveness was high, inclusive of those with low CD4 count and HIV viremia.

Background We previously demonstrated at the Ward 86 HIV clinic in San Francisco that long-acting cabotegravir/rilpivirine (LA-CAB/RPV) can rapidly lead to viral suppression (VS) in people with HIV (PWH) with viremia due to adherence challenges. We now evaluate VS durability in this population. Methods We conducted a retrospective cohort study of PWH who started LA-CAB/RPV with viremia (HIV RNA viral load [VL]≥50 copies/mL) before December 2022. Our primary outcome was VS (VL<50 copies/mL) with LA-CAB/RPV persistence (not discontinued or late by >14 days) at 48 weeks, using the closest VL to 48+/-8 weeks. We also describe viral failure (VF), defined as <2-log VL decline at 4 weeks or VL≥200 copies/mL after initial VS with emergent CAB- or RPV-associated resistance mutations; and overall 48-week VS including those switched to alternative ART. Results Fifty nine PWH initiated LA-CAB/RPV with viremia and were included in analysis; 49% had CD4<200 cells/µL and median baseline VL was 42,900 copies/mL (Q1-Q3 5,272-139,038). At 48 weeks, 47 met the primary outcome of VS with LA-CAB/RPV persistence (80%; 95%CI 67-89%). Five had VF with resistance (three with RPV-associated mutations, two with CAB and RPV-associated mutations) and one was lost-to-follow-up. At week 48, two of those with VF were suppressed on alternative regimens (lenacapavir+BIC/TAF/FTC and CAB+lenacapavir). Overall week 48 VS on either LA-CAB/RPV or alternative ART was 92% (54/59). Conclusions In PWH initiating LA-CAB/RPV with initial viremia, 48-week VS (<50 copies/mL) was 92%. Long-acting ART can be an important tool for improving VS among patients who face adherence challenges to oral ART.

The purpose of this article is to describe a model of chronic disease self-management that incorporates the complexity of social and environmental interactions experienced by people who self-manage chronic conditions. This study combines quantitative data from a large national research cohort and qualitative interviews to test and refine a self-management model. The self-management within a syndemic model depicts the contextual, psychological, and social factors that predict self-management behaviors and clinical and long-term outcomes.