Randomized Controlled Trial of 60 minutes for Health With Rapid Antiretroviral Therapy to Reengage Persons With HIV Who Are Out of Care.

BACKGROUND: Many persons with HIV remain out of care (PWH-OOC). We evaluated InstaCare, a complex intervention integrating the brief behavioral intervention 60 minutes for Health with the rapid restart of antiretroviral therapy (rapid ART). SETTING: Prospective open-label randomized controlled trial among PWH-OOC in San Diego, USA. METHODS: PWH-OOC were randomized 1:1 to InstaCare or a time-and-attention control integrating a diet-and-nutrition behavioral intervention also with rapid ART initiation (restart ≤7 days from enrollment). All participants had access to support services (free transport, HIV peer navigation, adherence counseling, and linkage to care) and primary care services (mental health, case management, social work, medication-assisted treatment, and specialist pharmacy). The primary outcomes were viral suppression (<50 copies/mL) and re-engagement with care (≥2 HIV care visits >90 days apart) by 24 weeks. Outcomes were reported on an intention-to-treat basis. RESULTS: Between November 2020 and August 2022, 52 PWH-OOC were enrolled. Baseline substance use in the preceding month (49%), unstable housing (51%), moderate/severe depression (49%), and moderate/severe anxiety (41.7%) were prevalent. Rapid ART was provided for all participants. At week 24, the proportion with HIV viral load <50 copies/mL was 37.3% (19/51) (InstaCare 28.0%, control 46.2%, P = 0.25). Fourteen (27.5%) were engaged with care (InstaCare 7/25 [28.0%], control 7/26 [26.9%], P = 1.00). Most participants (94%) reported low or very low emotional distress associated with rapid ART. Study lost to follow-up by week 24 was high (23/51, 45%). CONCLUSIONS: The InstaCare complex intervention did not improve viral suppression or reengagement with care among PWH-OOC. Investigation of high-intensity, individually adapted interventions is needed among PWH-OOC.

Relative Cost and Infectious Days Averted Associated With Rapid Gonorrhea and Chlamydia Testing Among Men Who Have Sex With Men.

BACKGROUND: Standard-of-care nucleic acid amplification tests (routine NAATs) for Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) can take several days to result and therefore delay treatment. Rapid point-of-care GC/CT NAAT (rapid NAAT) could reduce the time to treatment and therefore onward transmission. This study evaluated the incremental cost per infectious day averted and overall cost of implementation associated with rapid compared with routine NAAT. METHODS: Prospective sexually transmitted infection (STI) treatment data from men who have sex with men and transgender women in San Diego who received rapid NAAT between November 2018 and February 2021 were evaluated. Historical time from testing to treatment for routine NAAT was abstracted from the literature. Costs per test for rapid and routine NAAT were calculated using a micro-costing approach. The incremental cost per infectious day averted comparing rapid to routine NAAT and the costs of rapid GC/CT NAAT implementation in San Diego Public Health STI clinics were calculated. RESULTS: Overall, 2333 individuals underwent rapid NAAT with a median time from sample collection to treatment of 2 days compared with 7 to 14 days for routine NAAT equating to a reduction of 5 to 12 days. The cost of rapid and routine GC/CT NAAT was $57.86 and $18.38 per test, respectively, with a cost-effectiveness of between $2.43 and $5.82 per infectious day averted. The incremental cost of rapid NAAT improved when at least 2000 tests were performed annually. CONCLUSIONS: Although rapid GC/CT NAAT is more expensive than routine testing, the reduction of infectious days between testing and treatment may reduce transmission and provide improved STI treatment services to patients.

Annual N95 respirator fit-testing: an unnecessary burden on healthcare.

US regulations mandate annual N95 mask fit testing for healthcare workers, but the optimal testing interval is unknown. In our study using data from 12,565 healthcare workers, the probability of survival free from fit-test failure after 3 years was 99.4%, suggesting that less frequent fit testing every 3 years would be safe.

Effects of a hospital discharge clinic among people with HIV: Lack of early follow-up is associated with 30-day hospital readmission and decreased retention in care.

BACKGROUND: The transition between inpatient and outpatient care for hospitalized people with HIV represents an opportunity for linkage and re-engagement in care. We evaluated whether attendance at a post-hospitalization visit ('discharge clinic') within 1-2 weeks of discharge would reduce readmissions and improve retention in care (RIC) among people with HIV in San Diego, California, USA. METHODS: This was a retrospective cohort study of people with HIV hospitalized between June 2020 and November 2021. Our primary outcome was 30-day readmissions among people with HIV who did or did not attend a discharge clinic visit. Secondary outcomes included the effect of discharge clinic attendance on RIC, along with the impact of attendance at any HIV clinic visit within 30 days of discharge on readmissions and RIC. RESULTS: We evaluated 114 people with HIV, of whom 77 (67.5%) and 90 (78.9%) attended a discharge clinic visit or any HIV clinic visit within 30 days of discharge, respectively. Active substance use disorder (SUD) was associated with failing to attend a discharge clinic visit (odds ratio 0.31; 95% confidence interval 0.13-0.77). We observed no significant differences in readmissions between people with HIV who did or did not attend a discharge clinic visit; however, the former had significantly higher 6-month RIC (79.2% vs. 35.1%, p < 0.001). People with HIV attending any HIV clinic visit within 30 days of discharge had significantly fewer 30-day readmissions (8.9% vs. 29.2%, p = 0.02) and better 6-month RIC (75.6% vs. 25%, p < 0.001) than those who did not attend. CONCLUSION: Early hospital follow-up care was associated with a reduction in readmissions among people with HIV. Active SUD was a significant barrier to linkage to outpatient follow-up and RIC.

Risk of COVID-19 after natural infection or vaccination.

BACKGROUND: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. METHODS: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7-15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. FINDINGS: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05-0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01-0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. INTERPRETATION: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. FUNDING: National Institutes of Health.

Comparison of bivalent and monovalent SARS-CoV-2 variant vaccines: the phase 2 randomized open-label COVAIL trial.

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs and AEs of special interest. Boosting with prototype/wild-type vaccines produced numerically lower ID50 titers than any variant-containing vaccine against all variants. Conversely, boosting with a variant vaccine excluding prototype was not associated with decreased neutralization against D614G. Omicron BA.1 or Beta monovalent vaccines were nearly equivalent to Omicron BA.1 + prototype or Beta + prototype bivalent vaccines for neutralization of Beta, Omicron BA.1 and Omicron BA.4/5, although they were lower for contemporaneous Omicron subvariants. Safety was similar across arms and stages and comparable to previous reports. Our study shows that updated vaccines targeting Beta or Omicron BA.1 provide broadly crossprotective neutralizing antibody responses against diverse SARS-CoV-2 variants without sacrificing immunity to the ancestral strain. ClinicalTrials.gov registration: NCT05289037 .

Cardiovascular Outcomes After Tixagevimab and Cilgavimab use for Pre-Exposure Prophylaxis Against Coronavirus Disease 2019: A Population-Based Propensity-matched Cohort Study.

Tixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.

4th Generation HIV screening in the emergency department: net profit or loss for hospitals?

ABSTRACTThe objective of this study was to determine hospital costs and revenue of universal opt-out HIV ED screening. An electronic medical record (EMR)-directed, automated ED screening program was instituted at an academic medical center in San Diego, California. A base model calculated net income in US dollars for the hospital by comparing annual testing costs with reimbursements using payor mixes and cost variables. To account for differences in payor mixes, testing costs, and reimbursement rates across hospitals in the US, we performed a probabilistic sensitivity analysis. The base model included a total of 12,513 annual 4th generation HIV tests with the following payor mix: 18% Medicare, 9% MediCal, 28% commercial and 8% self-payers, with the remainder being capitated contracts. The base model resulted in a net profit for the hospital. In the probabilistic sensitivity analysis, universal 4th generation HIV screening resulted in a net profit for the hospital in 81.9% of simulations. Universal 4th generation opt-out HIV screening in EDs resulted in a net profit to an academic hospital. Sensitivity analysis indicated that ED HIV screening results in a net-profit for the majority of simulations, with higher proportions of self-payers being the major predictor of a net loss.

Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19.

The return of COVID-19 symptoms after Nirmatrelvir/Ritonavir (Nm/R) treatment is being increasingly reported. Limited evidence suggests most cases of rebound symptoms are mild and do not require further intervention. Here we present a male veteran reporting rebound symptoms who was found to be hypoxic with pulmonary emboli. Our case highlights the need to evaluate known complications of SARS-CoV-2 including venous thromboembolism in patients reporting recurring symptoms. Further, cases of severe rebound phenomenon should continue to be reported by clinicians to better appreciate the use of the Nm/R during the Omicron wave and among vaccinated persons.

SARS-CoV-2 Variant Vaccine Boosters Trial: Preliminary Analyses.

Background: Protection from SARS-CoV-2 vaccines wanes over time and is compounded by emerging variants including Omicron subvariants. This study evaluated safety and immunogenicity of SARS-CoV-2 variant vaccines. Methods: This phase 2 open-label, randomized trial enrolled healthy adults previously vaccinated with a SARS-CoV-2 primary series and a single boost. Eligible participants were randomized to one of six Moderna COVID19 mRNA vaccine arms (50µg dose): Prototype (mRNA-1273), Omicron BA.1+Beta (1 or 2 doses), Omicron BA.1+Delta, Omicron BA.1 monovalent, and Omicron BA.1+Prototype. Neutralization antibody titers (ID 50 ) were assessed for D614G, Delta, Beta and Omicron BA.1 variants and Omicron BA.2.12.1 and BA.4/BA.5 subvariants 15 days after vaccination. Results: From March 30 to May 6, 2022, 597 participants were randomized and vaccinated. Median age was 53 years, and 20% had a prior SARS-CoV-2 infection. All vaccines were safe and well-tolerated. Day 15 geometric mean titers (GMT) against D614G were similar across arms and ages, and higher with prior infection. For uninfected participants, Day 15 Omicron BA.1 GMTs were similar across Omicron-containing vaccine arms (3724-4561) and higher than Prototype (1,997 [95%CI:1,482-2,692]). The Omicron BA.1 monovalent and Omicron BA.1+Prototype vaccines induced a geometric mean ratio (GMR) to Prototype for Omicron BA.1 of 2.03 (97.5%CI:1.37-3.00) and 1.56 (97.5%CI:1.06-2.31), respectively. A subset of samples from uninfected participants in four arms were also tested in a different laboratory at Day 15 for neutralizing antibody titers to D614G and Omicron subvariants BA.1, BA.2.12.2 and BA.4/BA.5. Omicron BA.4/BA.5 GMTs were approximately one third BA.1 GMTs (Prototype 517 [95%CI:324-826] vs. 1503 [95%CI:949-2381]; Omicron BA.1+Beta 628 [95%CI:367-1,074] vs. 2125 [95%CI:1139-3965]; Omicron BA.1+Delta 765 [95%CI:443-1,322] vs. 2242 [95%CI:1218-4128] and Omicron BA.1+Prototype 635 [95%CI:447-903] vs. 1972 [95%CI:1337-2907). Conclusions: Higher Omicron BA.1 titers were observed with Omicron-containing vaccines compared to Prototype vaccine and titers against Omicron BA.4/BA.5 were lower than against BA.1 for all candidate vaccines. Clinicaltrialsgov: NCT05289037.

Risk of hepatitis C reinfection following successful therapy among people living with HIV: a global systematic review, meta-analysis, and meta-regression.

BACKGROUND: The benefits of direct-acting antivirals towards the elimination of hepatitis C virus (HCV) in people living with HIV are decreased when individuals are reinfected with HCV following treatment. We aimed to systematically review the existing evidence of HCV reinfection risk after treatment among people living with HIV, including people who inject drugs and men who have sex with men (MSM), and to identify the factors that explain heterogeneity in the incidence of HCV reinfection. METHODS: For this systematic review and meta-analysis, we searched PubMed, Scopus, Web of Science, Cochrane, PsycINFO, and conference presentations from date of database inception to Jan 10, 2022, for clinical trials and cohort studies providing data that could be used to calculate the incidence of HCV reinfection following HCV treatment. Random-effect meta-analysis models were used to calculate rate estimates. Study-level factors contributing to heterogeneity of reinfection estimates were assessed using meta-regression. This study is registered with PROSPERO, CRD42019146973. FINDINGS: 41 studies, predominantly conducted in Europe, were included, with a total of 9024 participants. The incidence of reinfection was 3·76 cases per 100 person-years of follow-up (95% CI 2·80-5·05; I2 85·9%) among people living with HIV overall, 6·01 (4·54-7·95; 74·1%) among MSM, and 3·29 (2·01-5·39; 83·9%) among people who inject drugs. A similar incidence of reinfection was observed following interferon-based therapy (4·92 cases per 100 person-years of follow-up, 3·30-7·32; I2 78·3%) and direct-acting antiviral therapy (3·88, 2·51-6·01; 85·4%). A higher proportion (≥85%) of MSM in the study population (adjusted rate ratio 2·66, 95% CI 1·37-5·15) and recent HCV infection (2·22, 1·09-4·55) were associated with an increased incidence of reinfection; a longer duration of follow-up after treatment (0·97, 0·96-0·99) was associated with a decreased incidence. INTERPRETATION: Risk of HCV reinfection following treatment in people living with HIV was highest among MSM and those with recent HCV infection. Continued scale-up of HCV treatment and ongoing HCV screening and treatment of infection in this patient population should reduce viraemic burden and risk of reinfection. FUNDING: None.

Sex differences in type 2 diabetes mellitus prevalence among persons with HIV.

OBJECTIVE: To examine whether type 2 diabetes mellitus (T2DM) is more common among women with HIV (WWH) than men with HIV (MWH). DESIGN: A cross-sectional analysis of a demographically heterogenous population-based sample of more than 64 million patients in the United States. METHODS: Using the Explorys (IBM) database, compare the prevalence of T2DM among men and women without HIV and influence of HIV on T2DM by sex controlling for confounding factors. RESULTS: From 19 182 775 persons included in the study, 39 485 were with HIV. Rates of obesity was higher among WWH than MWH (58 vs. 35%). Prevalence of T2DM among WWH was 23% compared with 16% among MWH (P < 0.001). In sex-stratified adjusted analysis, WWH had 1.31 [95% confidence interval (CI), 1.24-1.38] times the odds of having T2DM than women without HIV. Women with HIV was associated with T2DM across all demographic subgroups. In contrast, no association between HIV and T2DM was observed among men (OR 1.01; 95% CI 0.98-1.05). CONCLUSION: These data suggest that HIV confers a sex-specific increase in odds of T2DM among women but not men.

Rapid Antiretroviral Therapy Among Individuals With Acute and Early HIV.

HIV transmission is increased during acute and early HIV (AEH). Rapid antiretroviral therapy may shorten the duration of infectivity. We show rapid antiretroviral therapy in AEH is acceptable and effective, with 69.0% of participants starting ART within 7 days of HIV diagnosis disclosure, and 88.1% achieving suppression by 48 weeks.

Tenofovir alafenamide and rifabutin co-administration does not lead to loss of HIV-1 suppression: A retrospective observational study.

OBJECTIVES: Tenofovir alafenamide (TAF) is a preferred nucleotide reverse transcriptase inhibitor used in the treatment of HIV. Co-administration of TAF with rifabutin (RFB) is not recommended due to concerns that RFB decreases TAF gastrointestinal absorption. The objective of this study was to determine the efficacy of antiretroviral therapy regimens that include the co-administration of TAF and RFB. METHODS: Persons with HIV (PWH) who received TAF-RFB co-administration for ≥1 month were identified retrospectively. The primary outcome was the maintenance of HIV viral load <200 copies/mL (cpm) for those already on HIV therapy at RFB initiation, or suppression of viral load to <200 cpm for those with unsuppressed HIV viral load prior to TAF-RFB co-administration. RESULTS: Twenty-two PWH met the inclusion criteria. Four out of five patients (80%) maintained a viral load <200 cpm and 15/17 (88%) achieved a viral load <200 cpm during TAF-RFB co-administration. After the exclusion of patients who self-discontinued therapy or were lost to follow-up, 19/19 (100%) met the combined primary endpoint of HIV viral load <200 cpm. CONCLUSIONS: This study suggests that TAF-RFB co-administration may be effective despite concerns that RFB could reduce TAF absorption.

Ceftaroline-associated Encephalopathy in Patients With Severe Renal Impairment.

Encephalopathy complicates beta-lactam therapy, particularly with impaired renal function, though no studies have reported ceftaroline-associated encephalopathy. Among 28 patients with estimated glomerular filtration rates <30 mL/min who received ≥5 days of ceftaroline, 3 developed encephalopathy. Ceftaroline, when dosed supra-therapeutically for serious infections, may be a cause of antibiotic-associated encephalopathy.

Genetic Network Analysis to Assess the Risk of Human Immunodeficiency Virus Transmission Among Men Who Have Sex With Men Seeking Partners on the Internet.

BACKGROUND: Online partner seeking (OPS) among men who have sex with men (MSM) is associated with increased risk behavior including frequency of unprotected anal intercourse, number of partners, and incidence of sexually transmitted infections (STIs). However, the impact on transmission of human immunodeficiency virus (HIV) is uncertain. METHODS: MSM diagnosed with acute and early HIV infection were recruited from the Primary Infection Resource Consortium. HIV transmission events in the year following infection were inferred using estimated date of infection combined with genetic network analysis with linked sequences defined as ≤0.015 sequences/site difference in the HIV type 1 (HIV-1) pol coding region. Participants completed a detailed baseline questionnaire including reported methods of meeting sexual partners, including OPS, in the prior 3 months, and regression was performed with inferred transmission as the outcome. RESULTS: From 147 MSM who completed the questionnaire, there were an associated 20 inferred HIV transmissions. No association with OPS was found (odds ratio, 0.64 [95% confidence interval, .24-1.69]; P = .37), though individuals who reported OPS were more likely to have reported a greater number of partners (P = .003) and prior STIs (P = .002). Geospatial analysis did not indicate that OPS was associated with increased geographical reach of the user (P = .68). CONCLUSIONS: Individuals reporting OPS did not have increased odds of inferred HIV-1 transmission in the year following infection using genetic linkage analysis despite apparently increased risk behavior. OPS also did not increase the geographic distance between genetically clustered HIV infections, suggesting that individuals mainly use the internet to meet partners in their local region.

Primary Incidence of Hepatitis C Virus Infection Among HIV-Infected Men Who Have Sex With Men in San Diego, 2000-2015.

BACKGROUND: Little is known about the hepatitis C virus (HCV) epidemic among HIV-infected men who have sex with men (HIV+ MSM) in the United States. In this study, we aimed to determine the incidence of primary HCV infection among HIV+ MSM in San Diego, California. METHODS: We performed a retrospective cohort analysis of HCV infection among HIV+ MSM attending 2 of the largest HIV clinics in San Diego. Incident HCV infection was assessed among HIV+ MSM with a negative anti-HCV test and subsequent HCV test between 2000 and 2017, with data censored to 2015. HCV reinfection was assessed among HIV+ MSM successfully treated for HCV between 2008 and 2015. Infection/reinfection rates were calculated using person-time methods. RESULTS: Among 3068 initially HCV-seronegative HIV+ MSM, 178 new infections occurred over 15 796 person-years, giving an incidence of 1.13 per 100 person-years (/100py; 95% confidence interval [CI], 0.97-1.31). Incidence was stable from 2000 to 2014 (0.83/100py; 95% CI, 0.41-1.48), with an increase to 3.01/100py (95% CI, 1.97-4.42) in 2015 (P = .02). Among 43 successfully treated patients, 3 were reinfected. CONCLUSIONS: HCV incidence is high among HIV+ MSM in San Diego, with evidence suggesting a recent increase in 2015. Strong HCV testing guidelines and active prevention efforts among HIV+ MSM are urgently needed that include rapid diagnosis, treatment, and risk reduction.