Human Immunodeficiency Virus Status, Tenofovir Exposure, and the Risk of Poor Coronavirus Disease 19 Outcomes: Real-World Analysis From 6 United States Cohorts Before Vaccine Rollout.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) may be at increased risk for severe coronavirus disease 2019 (COVID-19) outcomes. We examined HIV status and COVID-19 severity, and whether tenofovir, used by PWH for HIV treatment and people without HIV (PWoH) for HIV prevention, was associated with protection. METHODS: Within 6 cohorts of PWH and PWoH in the United States, we compared the 90-day risk of any hospitalization, COVID-19 hospitalization, and mechanical ventilation or death by HIV status and by prior exposure to tenofovir, among those with severe acute respiratory syndrome coronavirus 2 infection between 1 March and 30 November 2020. Adjusted risk ratios (aRRs) were estimated by targeted maximum likelihood estimation, with adjustment for demographics, cohort, smoking, body mass index, Charlson comorbidity index, calendar period of first infection, and CD4 cell counts and HIV RNA levels (in PWH only). RESULTS: Among PWH (n = 1785), 15% were hospitalized for COVID-19 and 5% received mechanical ventilation or died, compared with 6% and 2%, respectively, for PWoH (n = 189 351). Outcome prevalence was lower for PWH and PWoH with prior tenofovir use. In adjusted analyses, PWH were at increased risk compared with PWoH for any hospitalization (aRR, 1.31 [95% confidence interval, 1.20-1.44]), COVID-19 hospitalizations (1.29 [1.15-1.45]), and mechanical ventilation or death (1.51 [1.19-1.92]). Prior tenofovir use was associated with reduced hospitalizations among PWH (aRR, 0.85 [95% confidence interval, .73-.99]) and PWoH (0.71 [.62-.81]). CONCLUSIONS: Before COVID-19 vaccine availability, PWH were at greater risk for severe outcomes than PWoH. Tenofovir was associated with a significant reduction in clinical events for both PWH and PWoH.

Beyond Antiretroviral Treatment: Patterns and Factors Associated With Composite Medication Adherence Before and During the COVID-19 Pandemic in Patients With HIV With Multiple Chronic Conditions.

BACKGROUND: Polypharmacy for multiple chronic conditions (MCCs) poses an increasing challenge in people with HIV (PWH). This research explores medication adherence in PWH with MCCs before and during COVID-19. SETTING: Kaiser Permanente Mid-Atlantic States. METHODS: Medical and pharmacy records of a continuously enrolled cohort (September 2018-September 2021) of adult PWH were used. To estimate medication adherence, monthly proportion of days covered (PDC) was measured individually for antiretrovirals (ARVs), diabetes medications (DMs), renin-angiotensin antagonists (RASMs), and statins (SMs) and combined into composite measures (CMs) with and without ARVs. Descriptive statistics, time-series models, and multivariable population-averaged panel general estimating equations were used to profile trends, effects, and factors associated with adherence. RESULTS: The cohort (n = 543) was predominantly 51-64 years old (59.3%), Black (73.1%), male (69.2%), and commercially insured (65.4%). Two-thirds (63.7%) of patients were taking medications in 2 medication groups (ie, ARVs and either DMs, RASMs, or SMs), 28.9% were taking medications in 3 medication groups, and 7.4% were taking medications in all 4 medication groups. Overall, PDC for CMs without ARVs was 77.2% and 70.2% with ARVs. After March 2020, negative monthly trends in PDC were observed for CMs without ARVs (ß = -0.1%, P = 0.003) and with ARVs (ß = -0.3%, P = 0.001). For CMs with ARVs, Black race (aOR = 0.5; P < 0.001; ref: White) and taking medications for 3 medication groups (aOR = 0.8; P < 0.02; ref: 2) were associated with lower adherence. CONCLUSION: Decreasing medication adherence trends were observed during the COVID-19 pandemic with variations among population subgroups. Opportunity exists to improve medication adherence for non-White populations and those taking medications for MCCs beyond ARVs.

Post-acute sequelae of SARS-CoV-2 with clinical condition definitions and comparison in a matched cohort.

Disease characterization of Post-Acute Sequelae of SARS-CoV-2 (PASC) does not account for pre-existing conditions and time course of incidence. We utilized longitudinal data and matching to a COVID PCR-negative population to discriminate PASC conditions over time within our patient population during 2020. Clinical Classification Software was used to identify PASC condition groupings. Conditions were specified acute and persistent (occurring 0-30 days post COVID PCR and persisted 30-120 days post-test) or late (occurring initially 30-120 days post-test). We matched 3:1 COVID PCR-negative COVIDPCR-positive by age, sex, testing month and service area, controlling for pre-existing conditions up to four years prior; 28,118 PCR-positive to 70,293 PCR-negative patients resulted. We estimated PASC risk from the matched cohort. Risk of any PASC condition was 12% greater for PCR-positive patients in the late period with a significantly higher risk of anosmia, cardiac dysrhythmia, diabetes, genitourinary disorders, malaise, and nonspecific chest pain. Our findings contribute to a more refined PASC definition which can enhance clinical care.

Usefulness of Statins as Secondary Prevention Against Recurrent and Terminal Major Adverse Cardiovascular Events.

Clinical guidelines recommend statins for patients with atherosclerotic cardiovascular disease (ASCVD), but many remain untreated. The goal of this study was to assess the impact of statin use on recurrent major adverse cardiovascular events (MACE). This study used medical records and insurance claims from 4 health care systems in the United States. Eligible adults who survived an ASCVD hospitalization from September 2013 to September 2014 were followed for 1 year. A multivariable extended Cox model examined the outcome of time-to-first MACE, then a multivariable joint marginal model investigated the association between post-index statin use and nonfatal and fatal MACE. There were 8,168 subjects in this study; 3,866 filled a statin prescription ≤90 days before the index ASCVD event (47.33%) and 4,152 filled a statin prescription after the index ASCVD event (50.83%). These post-index statin users were younger, with more co-morbidities. There were 763 events (315/763, 41.3% terminal) experienced by 686 (8.4%) patients. The adjusted overall MACE risk reduction was 18% (HR 0.82, 95% CI 0.70 to 0.95, p = 0.007) and was more substantial in the first 180 days (HR 0.72, 95% CI 0.60 to 0.86, p <0.001). There was a nonsignificant 19% reduction in the number of nonfatal MACE (rate ratio 0.81, 95% CI 0.49 to 1.32, p = 0.394) and a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p <0.001). In conclusion, we found a modest increase in statin use after an ASCVD event, with nearly half of the patients untreated. The primary benefit of statin use was protection against early death. Statin use had the greatest impact in the first 6 months after an ASCVD event; therefore, it is crucial for patients to quickly adhere to this therapy.

Differences in COVID-19 testing and adverse outcomes by race, ethnicity, sex, and health system setting in a large diverse US cohort.

BACKGROUND: Racial/ethnic disparities during the first six months of the COVID-19 pandemic led to differences in COVID-19 testing and adverse outcomes. We examine differences in testing and adverse outcomes by race/ethnicity and sex across a geographically diverse and system-based COVID-19 cohort collaboration. METHODS: Observational study among adults (≥18 years) within six US cohorts from March 1, 2020 to August 31, 2020 using data from electronic health record and patient reporting. Race/ethnicity and sex as risk factors were primary exposures, with health system type (integrated health system, academic health system, or interval cohort) as secondary. Proportions measured SARS-CoV-2 testing and positivity; attributed hospitalization and death related to COVID-19. Relative risk ratios (RR) with 95% confidence intervals quantified associations between exposures and main outcomes. RESULTS: 5,958,908 patients were included. Hispanic patients had the highest proportions of SARS-CoV-2 testing (16%) and positivity (18%), while Asian/Pacific Islander patients had the lowest portions tested (11%) and White patients had the lowest positivity rates (5%). Men had a lower likelihood of testing (RR = 0.90 [0.89-0.90]) and a higher positivity risk (RR = 1.16 [1.14-1.18]) compared to women. Black patients were more likely to have COVID-19-related hospitalizations (RR = 1.36 [1.28-1.44]) and death (RR = 1.17 [1.03-1.32]) compared with White patients. Men were more likely to be hospitalized (RR = 1.30 [1.16-1.22]) or die (RR = 1.70 [1.53-1.89]) compared to women. These racial/ethnic and sex differences were reflected in both health system types. CONCLUSIONS: This study supports evidence of disparities by race/ethnicity and sex during the COVID-19 pandemic that persisted even in healthcare settings with reduced barriers to accessing care. Further research is needed to understand and prevent the drivers that resulted in higher burdens of morbidity among certain Black patients and men.

SARS-CoV-2 Testing and Positivity Among Persons With and Without HIV in 6 US Cohorts.

BACKGROUND: It is not definitively known if persons with HIV (PWH) are more likely to be SARS-CoV-2 tested or test positive than persons without HIV (PWoH). We describe SARS-CoV-2 testing and positivity in 6 large geographically and demographically diverse cohorts of PWH and PWoH in the United States. SETTING: The Corona Infectious Virus Epidemiology Team comprises 5 clinical cohorts within a health system (Kaiser Permanente Northern California, Oakland, CA; Kaiser Permanente Mid-Atlantic States, Rockville, MD; University of North Carolina Health, Chapel Hill, NC; Vanderbilt University Medical Center, Nashville, TN; and Veterans Aging Cohort Study) and 1 interval cohort (Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study). METHODS: We calculated the proportion of patients SARS-CoV-2 tested and the test positivity proportion by HIV status from March 1 to December 31, 2020. RESULTS: The cohorts ranged in size from 1675 to 31,304 PWH and 1430 to 3,742,604 PWoH. The proportion of PWH who were tested for SARS-CoV-2 (19.6%-40.5% across sites) was significantly higher than PWoH (14.8%-29.4%) in the clinical cohorts. However, among those tested, the proportion of patients with positive SARS-CoV-2 tests was comparable by HIV status; the difference in proportion of SARS-CoV-2 positivity ranged from 4.7% lower to 1.4% higher. CONCLUSIONS: Although PWH had higher testing proportions compared with PWoH, we did not find evidence of increased positivity in 6 large, diverse populations across the United States. Ongoing monitoring of testing, positivity, and COVID-19-related outcomes in PWH are needed, given availability, response, and durability of COVID-19 vaccines; emergence of SARS-CoV-2 variants; and latest therapeutic options.

Analysis of Postvaccination Breakthrough COVID-19 Infections Among Adults With HIV in the United States.

Importance: Recommendations for additional doses of COVID-19 vaccines for people with HIV (PWH) are restricted to those with advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk after vaccination among PWH is essential for informing vaccination guidelines. Objective: To estimate the rate and risk of breakthrough infections among fully vaccinated PWH and people without HIV (PWoH) in the United States. Design, Setting, and Participants: This cohort study used the Corona-Infectious-Virus Epidemiology Team (CIVET)-II (of the North American AIDS Cohort Collaboration on Research and Design [NA-ACCORD], which is part of the International Epidemiology Databases to Evaluate AIDS [IeDEA]), collaboration of 4 prospective, electronic health record-based cohorts from integrated health systems and academic health centers. Adult PWH who were fully vaccinated prior to June 30, 2021, were matched with PWoH on date of full vaccination, age, race and ethnicity, and sex and followed up through December 31, 2021. Exposures: HIV infection. Main Outcomes and Measures: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after a patient was fully vaccinated. Results: Among 113 994 patients (33 029 PWH and 80 965 PWoH), most were 55 years or older (80 017 [70%]) and male (104 967 [92%]); 47 098 (41%) were non-Hispanic Black, and 43 218 (38%) were non-Hispanic White. The rate of breakthrough infections was higher in PWH vs PWoH (55 [95% CI, 52-58] cases per 1000 person-years vs 43 [95% CI, 42-45] cases per 1000 person-years). Cumulative incidence of breakthroughs 9 months after full vaccination was low (3.8% [95% CI, 3.7%-3.9%]), albeit higher in PWH vs PWoH (4.4% vs 3.5%; log-rank P < .001; risk difference, 0.9% [95% CI, 0.6%-1.2%]) and within each vaccine type. Breakthrough infection risk was 28% higher in PWH vs PWoH (adjusted hazard ratio, 1.28 [95% CI, 1.19-1.37]). Among PWH, younger age (<45 y vs 45-54 y), history of COVID-19, and not receiving an additional dose (aHR, 0.71 [95% CI, 0.58-0.88]) were associated with increased risk of breakthrough infections. There was no association of breakthrough with HIV viral load suppression, but high CD4 count (ie, ≥500 cells/mm3) was associated with fewer breakthroughs among PWH. Conclusions and Relevance: In this study, COVID-19 vaccination, especially with an additional dose, was effective against infection with SARS-CoV-2 strains circulating through December 31, 2021. PWH had an increased risk of breakthrough infections compared with PWoH. Expansion of recommendations for additional vaccine doses to all PWH should be considered.

Analysis of Severe Illness After Postvaccination COVID-19 Breakthrough Among Adults With and Without HIV in the US.

Importance: Understanding the severity of postvaccination SARS-CoV-2 (ie, COVID-19) breakthrough illness among people with HIV (PWH) can inform vaccine guidelines and risk-reduction recommendations. Objective: To estimate the rate and risk of severe breakthrough illness among vaccinated PWH and people without HIV (PWoH) who experience a breakthrough infection. Design, Setting, and Participants: In this cohort study, the Corona-Infectious-Virus Epidemiology Team (CIVET-II) collaboration included adults (aged ≥18 years) with HIV who were receiving care and were fully vaccinated by June 30, 2021, along with PWoH matched according to date fully vaccinated, age group, race, ethnicity, and sex from 4 US integrated health systems and academic centers. Those with postvaccination COVID-19 breakthrough before December 31, 2021, were eligible. Exposures: HIV infection. Main Outcomes and Measures: The main outcome was severe COVID-19 breakthrough illness, defined as hospitalization within 28 days after a breakthrough SARS-CoV-2 infection with a primary or secondary COVID-19 discharge diagnosis. Discrete time proportional hazards models estimated adjusted hazard ratios (aHRs) and 95% CIs of severe breakthrough illness within 28 days of breakthrough COVID-19 by HIV status adjusting for demographic variables, COVID-19 vaccine type, and clinical factors. The proportion of patients who received mechanical ventilation or died was compared by HIV status. Results: Among 3649 patients with breakthrough COVID-19 (1241 PWH and 2408 PWoH), most were aged 55 years or older (2182 patients [59.8%]) and male (3244 patients [88.9%]). The cumulative incidence of severe illness in the first 28 days was low and comparable between PWoH and PWH (7.3% vs 6.7%; risk difference, -0.67%; 95% CI, -2.58% to 1.23%). The risk of severe breakthrough illness was 59% higher in PWH with CD4 cell counts less than 350 cells/µL compared with PWoH (aHR, 1.59; 95% CI, 0.99 to 2.46; P = .049). In multivariable analyses among PWH, being female, older, having a cancer diagnosis, and lower CD4 cell count were associated with increased risk of severe breakthrough illness, whereas previous COVID-19 was associated with reduced risk. Among 249 hospitalized patients, 24 (9.6%) were mechanically ventilated and 20 (8.0%) died, with no difference by HIV status. Conclusions and Relevance: In this cohort study, the risk of severe COVID-19 breakthrough illness within 28 days of a breakthrough infection was low among vaccinated PWH and PWoH. PWH with moderate or severe immune suppression had a higher risk of severe breakthrough infection and should be included in groups prioritized for additional vaccine doses and risk-reduction strategies.

Screening and Preventative Strategies for Patients at High Risk for Breast Cancer.

PURPOSE: Current US guidelines recommend more intensive breast cancer screening and preventive strategies for patients at more than 20% lifetime risk for breast and ovarian cancer (high risk for breast and ovarian cancer [HRBOC]). Guidelines recommend that yearly mammograms alternating with magnetic resonance imaging (MRI) screening should be considered as early as 30 years old. Furthermore, BRCA mutation carriers should consider bilateral mastectomy and bilateral oophorectomy after age 35. It was unclear what the uptake of screening and risk-reducing strategies were for patients who were cancer-free and cancer survivors seen by Kaiser Permanente Mid-Atlantic States (KPMAS) Genetics. METHODS: We retrospectively studied female patients (members of KPMAS between 2005 and 2016) diagnosed as HRBOC and/or tested for breast cancer-related mutations by KPMAS Genetics during 2013-2016. We identified cancer diagnoses, mammogram and breast MRI screening, mastectomies, and oophorectomies that occurred before and after the Genetics visit during the study period. RESULTS: Our cohort included 813 women with a HRBOC diagnosis, with a median 51 years of age at diagnosis, 45% White, 38% Black, and 15% other ethnicity. Most cancers occurred prior to the Genetics visit: 513/527 breast cancer diagnoses and 55/57 ovarian cancer diagnoses. Fewer than five prophylactic mastectomies and 89 prophylactic oophorectomies were identified. Among 228 patients who were 30-75 years old, breast cancer-free at the time of HRBOC diagnosis, and members for over 6 months, 190 (83%) had at least one screening test (mammogram or MRI) after the consultation with Genetic, but 79% never had an MRI before or after the consultation. CONCLUSION: Our findings suggest that earlier detection of patients with HRBOC and closer monitoring is needed.

COVID-19 infections post-vaccination by HIV status in the United States.

IMPORTANCE: Recommendations for additional doses of COVID vaccine are restricted to people with HIV who have advanced disease or unsuppressed HIV viral load. Understanding SARS-CoV-2 infection risk post-vaccination among PWH is essential for informing vaccination guidelines. OBJECTIVE: Estimate the risk of breakthrough infections among fully vaccinated people with (PWH) and without (PWoH) HIV in the US. DESIGN SETTING AND PARTICIPANTS: The Corona-Infectious-Virus Epidemiology Team (CIVET)-II cohort collaboration consists of 4 longitudinal cohorts from integrated health systems and academic health centers. Each cohort identified individuals ≥18 years old, in-care, and fully vaccinated for COVID-19 through 30 June 2021. PWH were matched to PWoH on date fully vaccinated, age group, race/ethnicity, and sex at birth. Incidence rates per 1,000 person-years and cumulative incidence of breakthrough infections with 95% confidence intervals ([,]) were estimated by HIV status. Cox proportional hazards models estimated adjusted hazard ratios (aHR) of breakthrough infections by HIV status adjusting for demographic factors, prior COVID-19 illness, vaccine type (BNT162b2, [Pfizer], mRNA-1273 [Moderna], Jansen Ad26.COV2.S [J&J]), calendar time, and cohort. Risk factors for breakthroughs among PWH, were also investigated. EXPOSURE: HIV infection. OUTCOME: COVID-19 breakthrough infections, defined as laboratory evidence of SARS-CoV-2 infection or COVID-19 diagnosis after an individual was fully vaccinated. RESULTS: Among 109,599 individuals (31,840 PWH and 77,759 PWoH), the rate of breakthrough infections was higher in PWH versus PWoH: 44 [41, 48] vs. 31 [29, 33] per 1,000 person-years. Cumulative incidence at 210 days after date fully vaccinated was low, albeit higher in PWH versus PWoH overall (2.8% versus 2.1%, log-rank p<0.001, risk difference=0.7% [0.4%, 1.0%]) and within each vaccine type. Breakthrough infection risk was 41% higher in PWH versus PWoH (aHR=1.41 [1.28, 1.56]). Among PWH, younger age (18-24 versus 45-54), history of COVID-19 prior to fully vaccinated date, and J&J vaccination (versus Pfizer) were associated with increased risk of breakthroughs. There was no association of breakthrough with HIV viral load suppression or CD4 count among PWH. CONCLUSIONS AND RELEVANCE: COVID-19 vaccination is effective against infection with SARS-CoV-2 strains circulating through 30 Sept 2021. PWH have an increased risk of breakthrough infections compared to PWoH. Recommendations for additional vaccine doses should be expanded to all PWH.