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  Conference on Retroviruses
and Opportunistic Infections
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Boston USA
March 6-10, 2021
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In-Hospital COVID-19 Outcomes Not
Worse With HIV in 6-Center UK Analysis
  CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021
Mark Mascolini
COVID-19 mortality was similar with and without HIV in a 249-person British case-control comparison, even before statistical adjustment for potential confounders [1]. And after adjustment for other factors, HIV infection did not carry a higher risk of worse in-hospital nondeath outcomes [1]. These findings generally agree with results of a US HIV/non-HIV comparison [2] and a systematic review [3]. But together the three studies leave unanswered questions about the impact of HIV on recovery from COVID-19.
The authors of the new study [1] cite two previous analyses that found an adjusted 2.9-fold [4] or 1.49-fold [5] higher death risk with HIV in COVID-19 patients. But Lee and colleagues [1] believe several limitations undermine the strength of these conclusions, including inaccurate primary care coding for HIV; use of nonmatched populations; lack of data on CD4 count, viral load, or HIV treatment; possible over-representation of HIV-positive people with worse outcomes; and the uncertainties of focusing on mortality endpoints.
The new retrospective matched-cohort analysis involved COVID-19 patients from 6 large hospital trusts across England [1]. It included all HIV-positive people 18 or older admitted to the hospital with PCR-confirmed COVID-19 between February 1, 2020 and May 31, 2020. The researchers matched this HIV group in a 3-to-1 ratio to HIV-negative COVID-19 patients by hospital of admission, gender, SARS-CoV-2 test date (+/- 7 days), age (+/- 5 years), and index of multiple deprivation decile (IMDD)* (+/- 1).
The primary study outcome was time from COVID-19 diagnosis to hospital discharge or at least a 2-point improvement on a 7-point ordinal scale. The researchers used multivariable Cox proportional hazards regression to identify independent predictors of improvement then performed several sensitivity analyses, such as excluding missing data, excluding ethnicity, and adjusting for age. Cox model covariates were ethnicity, clinical frailty score, body mass index, hypoxia at admission, duration of symptoms before diagnosis, hypertension, diabetes, and chronic kidney disease.
The analysis focused on 68 people with HIV matched to 181 HIV-negative controls. The HIV and non-HIV groups matched closely on median age (57 and 56), median IMDD (3 and 3), percent female (38% and 37%), and baseline 7-point ordinal scale. The HIV group had a significantly higher median frailty score (3 vs 2, P = 0.0069) and a significantly higher proportion of black and minority ethnicities (75% vs 49%, P = 0.0002). Comorbidities more prevalent with HIV were end-stage renal failure requiring dialysis, stage 3 or worse chronic kidney disease, and liver disease. Comorbidities more prevalent in the non-HIV group were rheumatologic disease and asthma.
An unadjusted analysis determined that the HIV group had about a 45% lower chance of attaining the primary outcome (time to clinical improvement or discharge) (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.39 to 0.85, P = 0.005). But risk of 28-day mortality did not differ significantly between the HIV and HIV-negative groups in an unadjusted analysis (HR 1.18, 95% CI 0.54 to 2.60, P = 0.68).
In multivariate analysis, HIV infection had a much-attenuated (and nonsignificant) impact on time to clinical improvement or discharge (adjusted HR [aHR] 0.70, 95% CI 0.43 to 1.17, P = 0.18). But three factors did independently predict worse time to clinical improvement or discharge:
- Each 1-unit higher frailty score: aHR 0.79, 95% CI 0.65 to 0.95, P = 0.011
- Body mass index below 25 kg/m2: aHR 0.46, 95% CI 0.21 to 0.99, P = 0.047
- Active malignancy: aHR 0.37, 95% CI 0.17 to 0.82, P = 0.014
In sensitivity analyses, excluding or adding factors to the unadjusted analysis yielded a lower chance of clinical improvement or discharge in the HIV group, but the last two of these three associations stopped short of statistical significance:
- Excluding ethnicity: aHR 0.62, 95% CI 0.39 to 0.96, P = 0.031
- Excluding COVID-related factors (hypoxia, symptom duration): aHR 0.68, 95% CI 0.43 to 1.06, P = 0.088
- Adding age: aHR 0.67, 95% CI 0.42 to 1.06, P = 0.088
Among secondary outcomes, people with HIV did significantly worse than the HIV-negative group by only one measure: longer median days in hospital days (10 vs 7.5, P = 0.0061).
The researchers concluded that the unadjusted mortality rate did not differ significantly between COVID-19 inpatients with or without HIV. And after adjustment for comorbidities and demographics, HIV infection did not have a significant impact on time to clinical improvement or discharge. But baseline frailty and active malignancy remained independently associated with slower time to clinical improvement or discharge. The last conclusion suggests that some HIV populations, burdened by a higher prevalence of certain comorbidities like frailty or cancer, may face slower improvement from COVID-19 in the hospital.
A US comparison of 21 people with COVID-19 and HIV matched to 42 HIV-negative COVID-19 patients documented nonsignificant trends toward higher rates of intensive care unit admission, mechanical ventilation, and mortality in the HIV group [2]. People with HIV had significantly higher admission and peak C-reactive protein values than HIV-negative people, but other inflammatory markers did not differ between the groups. Three people with HIV and bacterial pneumonia died in the hospital.
Systematic review of 8 studies including 70 people with HIV and COVID-19 found no strong evidence that "controlled HIV infection" resulted in worse COVID-19 outcomes [3]. But the analysis could not establish whether people with "poorly controlled HIV and AIDS" have worse outcomes than HIV-negative people.
*"IMDD is a national index which ranks areas in England from most deprived to least deprived. Ethnicity was not included in the matching criteria as ethnicity data are often poorly defined and collected."
1. Not hospitalized, resumption of normal activities
2. Not hospitalized, unable to resume normal activities
3. Hospitalized, not requiring supplemental oxygen 4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive ventilation or both
6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both
7. Death or palliation
1. Lee MJ, Smith C, Fidler S, et al. HIV and COVID-19 inpatient outcomes: a matched retrospective multicentre analysis. CROI 2021, Conference on Retroviruses and Opportunistic Infections, March 6-10, 2021. Abstract 142. 2. Karmen-Tuohy S, Carlucci PM, Zervou FN, et al. Outcomes among HIV-positive patients Hospitalized With COVID-19. J Acquir Immune Defic Syndr. 2020;85:6-10. doi: 10.1097/QAI.0000000000002423. https://journals.lww.com/jaids/Fulltext/2020/09010/
3. Cooper TJ, Woodward BL, Alom S, et al. Coronavirus disease 2019 (COVID-19) outcomes in HIV/AIDS patients: a systematic review. HIV Med. 2020 Oct;21(9):567-577. doi:
10.1111/hiv.12911. https://onlinelibrary.wiley.com/doi/10.1111/hiv.12911 4. Bhaskaran K, Rentsch CT, MacKenna B, et al. HIV infection and COVID-19 death: a population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. Lancet HIV. 2020; 0. DOI:10.1016/S2352-3018(20)30305-2.
5. Geretti AM, Stockdale AJ, Kelly SH, et al. Outcomes of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical Characterization Protocol (UK): a prospective observational study. Clin Infect Dis 2020; published online Oct 23. DOI:10.1093/cid/ciaa1605.