Underlying health conditions play a major role in increased risk of hospitalisation with COVID-19 in people with HIV

Higher rates of hospitalisation or worse outcomes after admission for COVID-19 in people living with HIV are partially explained by underlying health conditions, especially heart disease and kidney disease, two studies from the United Kingdom and the United States have found.

But whereas British research found that the higher risk of COVID-19 in people with HIV was entirely attributable to underlying health conditions and greater physical frailty, the US study found a small but statistically significant increase in the risk of hospitalisation for COVID-19, even after controlling for some underlying conditions. Differences in methodology may explain the differing conclusions – whereas the British study matched cases in people with HIV to cases in the rest of the population to reduce distortions, the US study looked at outcomes for people with HIV within a much larger sample, but without matching.

The studies were presented this week at the 2021 virtual Conference on Retroviruses and Opportunistic Infections (CROI).

Several studies, in New York and the United Kingdom, have shown higher rates of hospitalisation for COVID-19 among people with HIV in the first wave of the pandemic in 2020. A low CD4 count and underlying health conditions emerged as the key risk factors for hospitalisation in people with HIV.

Several studies carried out in the UK found an increased risk of death from COVID-19 in people living with HIV, but it’s unclear how much these results were affected by the presence of underlying conditions such as heart disease, high blood pressure, diabetes and kidney disease that are known to raise the risk of death from COVID-19.

RECEDE: UK six-hospital study

Dr Ming Lee of Guy’s and St Thomas’s Hospital, London, reported the findings of the RECEDE study, designed to look carefully at the effects of HIV status on COVID-19 outcomes in people living with HIV. The study matched people living with HIV admitted to hospital with COVID-19 up to 31 May 2020, with HIV-negative people by hospital, age, gender, COVID-19 diagnosis date and deprivation index. The study matched people admitted at six hospitals in London, Leicester and Manchester.

The primary outcome of the study was the time to improvement in COVID-19 status or discharge from hospital, within 28 days of hospital admission. Improvement was measured on a 7-point scale, from death or palliative care, to not hospitalised and able to resume normal activities. Improvement was defined as a change of at least two points on the scale.

The researchers looked at all admissions between 1 February and 31 May 2020 and identified 69 people living with HIV among 6612 people admitted to the six hospitals with COVID-19. These people were matched with 181 HIV-negative people (one person with HIV could not be matched).

People with HIV were significantly more likely to be Black or of minority ethnicity (75 vs 49%, p = 0.0002), and had a higher median clinical frailty score. There was no difference between people with HIV and the control group in the frequency of severe illness requiring oxygen or mechanical ventilation.

People with HIV had been diagnosed with HIV for a median of 14.8 years, the median CD4 count was 352 cells and all but two had viral load below 200.

Several co-morbidities strongly associated with poorer COVID-19 outcomes were significantly more common in people with HIV, including end-stage renal disease (19 vs 5%, p = 0.005), chronic kidney disease (35 vs 12%, p < 0.0001) and liver cirrhosis (4.4 vs 0.6%, p = 0.031). Rheumatological disease (5.9 vs 10.5%, p = 0.0054) and asthma (13.3 vs 4.4%, p = 0.045) were more common in HIV-negative people. Diabetes and hypertension were common regardless of HIV status; 26% of people with HIV and 29% of HIV-negative people had diabetes, while 40% of HIV-negative people and 51% of people with HIV had a history of high blood pressure.

After admission to hospital, people with HIV were 43% less likely to experience the primary outcome, improvement by at least two points on the COVID severity scale (hazard ratio 0.57, 95% CI 0.39-0.85, p = 0.005), but did not have a higher risk of death within 28 days of COVID-19 diagnosis.

However, in a multivariable analysis that adjusted for confounding factors including body mass index, clinical frailty, hypoxia at admission, ethnicity, duration of symptoms prior to diagnosis, hypertension, diabetes and chronic kidney disease, HIV status ceased to be a risk factor for lack of improvement.

Instead, the analysis showed that active malignancy (HR 0.37, 95% CI 0.17-0.82, p = 0.014) and higher clinical frailty score (0.79, 95% CI 0.65-0.95, p = 0.011) were associated with longer time to clinical improvement or discharge.

The only difference in secondary outcomes between people with HIV and the control group was the median duration of hospital stay. People with HIV spent a median of ten days in hospital compared to 7.5 days for the control group (p = 0.0061).

"When people with HIV are admitted to hospital with COVID-19, it’s important not just to consider their HIV status, but the broader picture of comorbidities."

Dr Lee stressed the importance of appropriate matching in case-control studies to help clinicians understand which people with HIV are at greater risk of worse COVID-19 outcomes.

“People with HIV often have co-morbidities and greater frailty, so that could be contributing to their greater risk,” he told a question-and-answer session after his presentation. “When people with HIV are admitted to hospital with COVID-19, it’s important not just to consider their HIV status, but the broader picture of co-morbidities.”

“If someone has got well-controlled HIV, that should weigh a lot less strongly compared to other co-morbidities that might be contributing to their risk,” he concluded.

US: National COVID Cohort Collaborative

Dr Jing Sun of Johns Hopkins University, Baltimore, reported on the risk of severe COVID-19 outcomes in people with HIV and people who received solid organ transplants at 39 hospitals in the United States. The study was designed to compare the risks of severe COVID-19 in two groups of people with immunosuppression and the wider population, and to determine if COVID-19 has a similar impact regardless of the cause of immunosuppression.

The total study population comprised 509,092 cases of COVID-19 diagnosed by PCR or antigen testing between 1 January 2020 and 6 February 2021. The researchers calculated the risks of hospitalisation and mechanical ventilation, according to immunosuppression status.

Of the 509,092 people in the cohort, 2932 were people living with HIV, 4633 were organ transplant recipients and 111 were HIV-positive transplant recipients.

The rate of hospitalisation was higher in people with HIV (48.5%), organ transplant recipients (63.8%) and HIV-positive transplant recipients (70.3%) compared to HIV-negative people (30.6%). Rates of mechanical ventilation were also higher (5.5%, 9.9%, 20% and 1.9% respectively).

The odds of hospitalisation were raised for each of the three groups. After controlling for age, sex, race, ethnicity and co-morbidities (cancer, diabetes, severe liver disease, kidney disease and number of co-morbidities) people with HIV were at 32% higher risk of hospitalisation and transplant recipients at 69% higher risk of hospitalisation. People with HIV and transplant recipients were at 86% and 96% higher risk of mechanical ventilation after controlling for confounding factors.

Find out more: COVID-19 and coronavirus in people living with HIV

Several co-morbidities raised the risk of hospitalisation in people living with HIV. People with a history of heart attack were around 60% more likely to be hospitalised, while stroke and pulmonary disease increased the risk by around 50% and vascular disease by 43%. The greatest increase in risk was associated with congestive heart failure and chronic kidney disease, both of which more than doubled the risk of hospitalisation (odds ratios 2.27 and 2.28 respectively). All these differences were statistically significant. Liver disease, diabetes and cancer did not increase the likelihood that people with HIV would be admitted to hospital.

Dr Sun said that although the effect of HIV on risk of hospitalisation weakened when the analysis was adjusted for the presence of co-morbidities, they still found that people with HIV in the United States were at increased risk of severe COVID-19 outcomes.