Early studies examining the impact of HIV status on COVID-19 clinical outcomes, performed predominantly in hospitalized cohorts, suggested similar or better outcomes for people with HIV (PWH) compared with the general population . However, hospitalized cohorts are susceptible to bias, particularly if the threshold for admission among PWH could be lower than that for people without HIV [1–4]. More recently, large population-based studies, including one in New York State, have demonstrated increased mortality risk among PWH from COVID-19 [2–4]. Given the heterogeneity in SARS-CoV-2 susceptibility [4–6] and clinical COVID-19 outcomes among cohorts of PWH , we performed a large population-based study in San Francisco. This study examines the impact of HIV status on COVID-19 outcomes within a municipal primary care health system containing one of San Francisco's largest HIV clinics, Ward 86, over the first year of the COVID-19 pandemic.
Materials and methods
We conducted a population-level match of the COVID-19 registry of the San Francisco Department of Public Health (SFDPH) with the clinic rosters of the San Francisco Primary Care Clinics (SFPCC) from February 1, 2020, to March 1, 2021, including individuals with at least one visit in the prior 2 years. The SFDPH COVID-19 testing registry is a centralized reporting system capturing COVID-19 diagnoses, given that COVID-19 is a reportable illness locally. The SFPCC is a safety-net municipal health system administered by the SFDPH compromising 12 adult medicine clinics, including one of the largest HIV clinics in San Francisco, Ward 86. We examined the COVID-19 attack rate and testing rate among the full prospective cohort by HIV status using Poisson mixed models with a random-effects for the individual patient identifier. To examine the severity of COVID-19 clinical outcomes by HIV status, we performed a case--cohort study and assessed need for supplemental oxygen, use of a ventilator, and COVID-19-related death through in-depth chart review . We performed chart review among all PWH with positive SARS-CoV-2 tests, and randomly sampled 591 adults without HIV with positive SARS-CoV-2 from the two largest adult medicine clinics within the health network. To assess risk of hospitalization, severe COVID-19, and death, we performed binomial relative risk regression, with the inclusion of probability weights and robust standard errors to account for the sampling fraction .
Attack and testing rate
Overall, there were 22 024 participants examined over 25 630 person-years at risk in the SFPCC system, of whom 2690 were PWH examined over 3168 person-years (Table 1). The SARS-CoV-2 incidence was 79.1 per 1000 person-years [95% confidence interval (CI): 75.6–83.9] among people without HIV and 34.7 per 1000 person-years (95% CI 37.0–51.6) among PWH. When adjusting for age, sex, and race/ethnicity, the rate of SARS-CoV-2 infection was 40% lower among PWH [adjusted rate ratio (ARR) 0.60, 95% CI: 0.50–0.72]. The rate of SARS-CoV-2 infection was 210% higher among Latinx vs. white individuals (adjusted relative risk [ARR] 3.10, 95% CI: 2.65–3.63). The rate of SARS CoV-2 testing was 8% higher among PWH (ARR 1.08, 95% CI: 1.05–1.11) than among people without HIV.
Table 1 -
Population characteristics and clinical outcomes among people diagnosed with COVID-19.
||Overall population (n = 22 024)
||Diagnosed with COVID-19 (n = 1915)
|Median age (IQR)
|Female sex % (n)
||50% (11 036)
| American Indian % (n)
| Asian % (n)
| Black % (n)
| Latinx % (n)
| White % (n)
| Pacific Islander % (n)
| Mixed/Other % (n)
|People with HIV (PWH) % (n)
|COVID-19 incident infection
| Adjusted rate ratioa (95% CI) for COVID-19 infection for PWH
||0.60 (95% CI: 0.50–0.72)
| With HIV % (n)c
| Without HIV % (n)c
| Adjusted relative riskafor severe disease (95% CI) for PWH
||1.84 (95% CI: 1.05–3.25)
CI, confidence interval; IQR, interquartile range.aAdjusted for age, sex, and race/ethnicity.bDefined as hypoxia with oxygen saturation at least two readings requiring supplemental oxygen.cAmong all 136 PWH and 591 people without HIV randomly sampled for in-depth chart review.
Overall, there were 1915 cases of SARS-CoV-2 infection during this time-period, of which all PWH were sampled (136) and a random sub-cohort that included 591 people without HIV. After adjusting for age, sex, and race/ethnicity, the risk of hospitalization among those with SARS-CoV-2 was 90% higher among PWH (ARR 1.90, 95% CI: 1.21–2.98), while the risk of severe COVID-19 infection requiring supplemental oxygen was 84% higher among PWH (ARR 1.84, 95% CI: 1.05–3.25). The ARR for requiring a ventilator among PWH was 1.58 (95% CI: 0.52–4.83) and for death it was 1.90 (95% CI: 0.37–9.69). Among the 136 PWH with SARS-CoV-2 infection, 29 were admitted, 16 required supplemental oxygen, 4 required a ventilator, and 3 died from COVID-19. The risk of severe COVID-19 requiring supplemental oxygen was 30% lower for each 100 CD4+ cell increase in CD4+ cell count (RR 0.70, 95% CI: 0.49–0.99), while those with CD4+ cell counts less than 200 cells μl-1 had a 150% higher risk (relative risk [RR] 2.50, 95% CI: 1.01–6.19). The RR for requiring supplemental oxygen with a detectable vs. undetectable viral load was 1.3 (95% CI: 0.51–3.40).
In a population-based study of primary care patients over the first year following known SARS-CoV-2 community transmission within San Francisco, the risk of hospitalization and severe COVID-19 was higher among PWH with SARS-CoV-2 than those without HIV. These results echo large, population-based studies within New York State, Western Cape, South Africa, and in the UK [2–4]. Severe clinical outcomes appear most concentrated among PWH with low CD4+ cell counts, presumably related to suppressed or a dysregulated immune response to respiratory infection among PWH [2,4,8]. SARS-CoV-2 vaccination is expected to attenuate this risk among PWH .
SARS-CoV-2 incidence was lower among PWH despite somewhat greater testing rates in this group, and is similar to the difference estimated via a prior seroprevalence study within a subset of these populations . This finding may reflect lower exposure to SARS-CoV-2 among PWH, potentially related to greater adherence to nonpharmaceutical interventions such as physical distancing due to self-perception of higher SARS-CoV-2 risk . As vaccine distribution was just beginning at the end of the study period, it is unlikely that these results are influenced by differential vaccination rates.
Limitations of this analysis include our inability to adjust for other comorbid medical conditions impacting severe COVID-19. Higher testing rates among PWH could also potentially lead to greater detection of asymptomatic infections among PWH. However, greater detection of asymptomatic infections would not be expected to qualitatively impact our results, as this bias would lead to an underestimation of COVID-19 disease severity among PWH and an overestimation of the SARS-CoV-2 attack rate. Finally, our results should be considered reflective of individuals engaged in primary care within the SFPCC and may not reflect individuals in San Francisco not engaged in primary care.
The higher attack rate among Latinx individuals within this cohort reflects the known epidemic dynamics within San Francisco, influenced by underlying health disparities . Outreach and prioritization campaigns for SARS-CoV-2 vaccination should target the populations disproportionately impacted by COVID-19, as well as populations with potentially higher risk of severe outcomes, including PWH.
This research was supported by U.S. National Institute of Allergy and Infectious Diseases (NIAID) R01AI158013 (M.A.S. and M.G.), and U.S. NIAID P30AI027763 (M.G.).
Conflicts of interest
The authors have no conflicts of interest to report.
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