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HIV

Last reviewed: January 27, 2021

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Overview

Current recommendations for COVID-19 managementdiagnostic evaluation and infection prevention in people living with HIV (PLWH) do not differ from the general population. However, PLWH face adverse social determinants of health as well as medical comorbidities, and the risk of infection and poor outcomes for both COVID-19 and HIV is known to be higher among people of color (Price-Haywood, June 2020; Nydegger, June 2020; Millett, October 2020). It is not yet known what effect SARS-CoV-2 infection and COVID-19 disease may have on HIV viral replication, metabolism/efficacy of antiretroviral therapy and susceptibility to other HIV-associated morbidity.

COVID-19 vaccine safety and efficacy data specific to people with HIV is not yet available, but CDC advises that people with HIV should be eligible to receive the vaccines currently available in the U.S. as long as they do not have any contraindications, as they may be risk for serious illness due to COVID-19. See HIVMA's COVID-19 Vaccines and People with HIV FAQ for more information.

Risk of COVID-19 Infection in PLWH

Current data generally shows that PLWH have similar COVID-19 incidence and severity risk as people without HIV, after controlling for comorbidities such as elevated body mass index, diabetes mellitus and kidney disease. However, the majority of these observational studies include people who are on antiretroviral therapy and are virologically suppressed. Additional large population-based studies are needed to determine whether PLWH are at higher risk of COVID-19 after adjusting for known independent risk factors for the acquisition of and adverse outcomes in COVID-19. Larger studies are also needed to examine whether low CD4 or unsuppressed viral load are associated with increased risk of COVID-19 disease; to date, the literature is mixed. It is also not yet known what effect SARS-CoV-2 infection and COVID-19 disease may have on HIV viral replication, metabolism/efficacy of antiretroviral therapy, and susceptibility to other HIV-associated morbidity.

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COVID-19 Outcomes in PLWH

HIV infection, especially in those with unsuppressed HIV viral load and low CD4 count (<200 cells/μL), is a well-established risk factor for several viral opportunistic infections, including respiratory viral infections (Sellers, March 2020). It is therefore possible that PLWH with untreated HIV or advanced immunosuppression are at increased risk of poor outcomes from COVID-19.

Conversely, it has been proposed that immunosuppression could attenuate the immune activation associated with severe COVID-19, although the data is mixed in patients who have cancer, a solid organ transplant or take immunosuppressive medications. In two large population-based studies, one in New York State and one in South Africa, HIV was associated with approximately a two-fold overall risk of death; in one of the studies comorbidities known to be risk factors for severe COVID-19 and poor outcomes were not adjusted for (Tesoriero, November 2020). In the other some comorbidities were adjusted for, but several important ones (such as BMI) were not, and there were also high rates of tuberculosis (Boulle, August 2020).

Other published studies to date have not consistently found associations between HIV status and hospitalization, ICU admission or mortality. However, it does seem CD4 count <200 is consistently associated with poor outcomes. Because most persons in these analyses had suppressed HIV viral load, the risks due to untreated HIV are less clear.

Antiretroviral Therapy

Early in the pandemic it was hypothesized that protease inhibitors, specifically lopinavir/ritonavir, could have activity against SARS-CoV-2. This was primarily driven by the fact that:  lopinavir/ritonavir has in-vitro activity against MERS-CoV and SARS-CoV, albeit at much higher concentrations that what are typically used in humans (Yao, February 2020); that studies during the SARS epidemic had suggested benefit (Chan, December 2003; Chu, March 2004); and that in animal studies of MERS there was benefit (Chan, December 2015).  Lopinavir/ritonavir was used widely early in the pandemic, particularly in China, but the subsequent results of published randomized controlled clinical trials have not shown benefit (Cao, May 2020; RECOVERY Collaborative Group, October 2020). In addition, in July WHO’s multi-country SOLIDARITY trial discontinued its lopinavir/ritonavir arm after an interim analysis found little or no reduction in the mortality of hospitalized COVID-19 patients when compared to standard of care. IDSA guidelines recommend against the use of lopinavir/ritonavir for treatment of patients with COVID-19, and NIH guidelines recommend against the use of lopinavir/ritonavir for treatment of patients with COVID-19 outside of clinical trials.

Several observational studies have found nucleoside reverse transcription inhibitors, specifically tenofovir disoproxil or tenofovir alafenamide, may be protective against acquiring SARS-CoV-2 and against severe outcomes (Del Amo, June 2020; Boulle, August 2020). However, these studies are limited by significant confounding. In addition, other observational studies have not found such a relationship between  tenofovir disoproxil / tenofovir alafenamide and risk of SARS-CoV-2 acquisition or severe outcomes (Vizcarra, May 2020; Ho, June 2020; Charre, October 2020). Additional data is forthcoming.

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Guidelines

Both the U.S. Department of Health & Human Services and IDSA/HIVMA make the following key recommendations regarding COVID-19 and PLWH:

  • Maintaining ART continuity in both people at risk for and with COVID-19.
  • Not adjusting patients’ ART regimens with a goal of preventing/mitigating COVID-19 infection, due to lack of data for the efficacy of any antiretroviral agent or combination (g., lopinavir/ritonavir, boosted darunavir, tenofovir disoproxil fumarate/emtricitabine) against SARS-CoV-2.
  • Maintaining a high awareness of COVID-19 infection and complications in PLWH due to possibility of more severe disease, especially in those with other high-risk comorbidities.
  • Not using HIV status in decision-making about potentially life-saving interventions or enrollment in clinical trials.

 

Key Literature

In summary: Current limited data does not suggest that HIV infection is an independent risk factor for acquisition of COVID-19, nor does it suggest an increased risk of adverse outcomes.

Elevated COVID-19 outcomes among persons living with diagnosed HIV infection in New York State: Results from a population-level match of HIV, COVID-19 and hospitalization databases (Tesoriero, November 2020).

Overall, in this large population-matched observational study, PLWH in New York State had higher rates of COVID-19 diagnoses and hospital-based mortality compared to those not living with HIV, but data was not adjusted for comorbidities.

Patient population:

  • PLWH with COVID-19 compared to people not living with HIV and COVID-19.
  • Researchers identified people diagnosed with COVID-19 through June 7, 2020 in the New York State electronic clinical laboratory reporting system, then made a determination of HIV status by evaluating the New York State HIV Surveillance Registry.

Primary endpoint:

  • The continuum of rates of COVID-19 diagnoses, hospitalizations and in-hospital deaths for PLWH compared to the non-PLWH population; factors associated with these outcomes among PLWH.

Key findings:

  • Among 108,062 PLWH in New York State, 2,988 were diagnosed with COVID-19 (rate: 27.65/1,000).
    • The unadjusted rate ratio comparing PLWH to non-PLWH was 1.43-fold higher (95% CI: 1.38-1.48); however, the adjusted diagnosis rate-ratio (sRR) of PLWH vs non-PLWH was 0.94 (95% CI: 0.91-0.97).
    • Per-population COVID-19 hospitalization was higher among PLWH (sRR 1.38; 95% CI 1.29-1.47)
  • Among PLWH who were diagnosed with COVID-19, nearly one-third (299.87 per 1,000) were hospitalized, a rate 1.83-fold (95% CI: 1.72-1.96) that of non-PLWH.
  • Among those hospitalized with COVID-19, no differences were seen in in-hospital death, comparing PLWH vs. non-PLWH (sRR: 0.96, 95% CI: 0.83-1.09).
  • Overall, 207 PLWH (rate: 1.92/1,000) had a COVID-19 diagnosis and died in the hospital, resulting in an sRR of 2.55 (95% CI: 2.22-2.93) compared to the rate of the non-PLWH population.
    • After adjustment, the sRR was 1.23 (95% CI: 1.13-1.48).
  • In the adjusted model, PLWH of older age, race and ethnicity not white non-Hispanic, and living in the regions of metropolitan NYC were significantly more likely to be diagnosed with COVID-19.
  • Those with unsuppressed viral load had 30% increased likelihood of hospitalization (aRR 1.54; 95% CI: 1.24-1.91).

Limitations:

  • Due to limitations of the data available, information on comorbidities and other demographics was not included or analyzed.
    • In other studies, once comorbidities are controlled for, differences in COVID-19 related outcomes between PLWH and non-PLWH disappear.
  • Differences in SARS-CoV-2 diagnosis propensity between PLWH and the non-PLWH population could alter the interpretation of some findings.
  • Information on disease severity upon hospitalization was not shared; it is therefore not possible to determine if the higher rate of hospitalizations among PLWH was due to higher disease severity, to patients being more likely to present to care or because their providers were more likely to hospitalize them due to having HIV as a comorbidity.

 

Characteristics and outcomes of COVID-19 in patients with HIV: a multicenter research network study (Hadi, November 2020).

Overall, in this propensity-matched observational study of a research network cohort, after adjusting for comorbidities, PLWH did not have a higher rate of COVID-related mortality than persons not living with HIV.

Patient population:

  • PLWH with COVID-19 who were part of a research network (TriNETX) that contains data on more than 50 million patients from more than 35 U.S. healthcare organizations.

Primary endpoint:

  • Mortality (within 30 days of COVID-19 diagnosis), hospitalization (within 30 days of COVID-19 diagnosis) and laboratory data (within 30 days of COVID-19 diagnosis).

Key findings:

  • 404 PLWH were identified among 50,167 patients with COVID-19.
  • PLWH were more likely to be men, African-American and obese and have concurrent hypertension, diabetes, chronic kidney disease and nicotine dependence compared with non-PLH cohort (all P values <0.05).
  • After propensity score matching for BMI, diabetes, hypertension, chronic lung disease, chronic kidney disease, race, history of nicotine dependence and sex, there was no difference in mortality between the groups (RR 1.33, 95% CI: 0.69–2.57).
  • A higher proportion of the PLWH group needed inpatient care (19.31 vs. 11.39%, RR 1.696, 95% CI: 1.21–2.38).
  • Mortality was not different for PLWH with a history of antiretroviral treatment.

Limitations:

  • Retrospective observational study; bias is possible.
  • Some bias may be inherent due to utilizing an electronic medical record-based database.

 

Lopinavir–ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomized, controlled, open-label, platform trial (The RECOVERY Collaborative Group, October 2020).

Overall, in this large randomized controlled trial of patients admitted to hospitals in the UK with COVID-19,  lopinavir/ritonavir did not reduce mortality or time to clinical improvement. The majority of patients in the study received lopinavir/ritonavir at the end of their week of illness, which may be too late for lopinavir/ritonavir to have an effect.

Patient population:

  • Patients admitted with COVID-19 disease to 176 National Health Service hospitals in the U.K., of whom 1616 patients were randomly allocated to receive lopinavir/ritonavir and 3424 patients to receive usual care.

Primary endpoint:

  • All-cause mortality within 28 days of randomization. 

Key findings:

  • The median time from symptom onset to randomization in the lopinavir/ritonavir group was 8 days (IQR 5–12) and in the usual care group it was also 8 days (IQR 4–12).
  • 374 (23%) patients allocated to lopinavir/ritonavir and 767 (22%) patients allocated to usual care died within 28 days (rate ratio 1.03, 95% CI: 0.91–1.17; p=0.60).
  • There was no difference in time until discharge alive from hospital (median 11 days [IQR 5 to >28] in both groups).
  • There was no difference in the proportion of patients discharged from hospital alive within 28 days (rate ratio 0.98, 95% CI: 0.91–1.05; p=0.53).
  • Among patients not on invasive mechanical ventilation at baseline, there was no significant difference in the proportion who met the composite endpoint of invasive mechanical ventilation or death (risk ratio 1.09, 95% CI: 0.99–1.20; p=0.092).

Limitations:

  • The mortality rate of patients with severe COVID-19 disease found in this study is higher than what has been generally found in this group in the United States.
  • Open-label design; researchers and patients in the study knew who was receiving which treatment. This could have introduced bias into the results.
  • Not all patients had proven SARS-CoV-2 infection via RT-PCR.
  • Most patients were at the end of their first week of illness, which may be too late for an antiviral to have an effect.

 

Disproportionate burden of coronavirus disease 2019 among racial minorities and those in congregate settings among a large cohort of people with HIV (Meyerowitz, October 2020).

Overall, in this small observational study of PLWH and COVID-19, the rate of comorbidities associated with severe COVID-19 was high, and a large proportion of the patients were non-Hispanic black or Hispanic/Latinx. Patients with mild or asymptomatic disease were not well-represented. The study is limited by a lack of a comparator group.

Patient population:

  • 36 confirmed and 11 probable cases of COVID-19 among PLWH in a single HIV clinic.

Primary endpoint:

  • Descriptive study evaluating the demographics, risk factors, clinical presentation and diagnosis of COVID-19.

Key findings:

  • Among the 36 PLWH with confirmed COVID-19, 21 required hospitalization, 8 had severe disease and 7 had critical illness.
  • 2 patients died and 4 remained hospitalized at the time of publication.
  • At presentation, 21 (58.3%) reported fever, 20 (55.6%) reported cough and 14 (38.9%) reported shortness of breath.
  • The average age was 53.4 years (range 24–81 years).
  • 2 patients had a CD4+ cell count <200 cells/μl, and 1 patient was not on ART.
    • Of patients on ART, 29/35 were on an integrase strand transfer inhibitor, 9 were on a nonnucleoside reverse transcriptase inhibitor and 4 were on protease inhibitors. Thirty were on a tenofovir-containing regimen.
  • Patients who required hospitalization were older than those who did not (55.9 versus 50 years, respectively).
  • 30 (83.3%) had comorbidities associated with severe COVID-19, including:
    • BMI >30 (12/36; 33.3%);
    • Hypertension (11/36; 30.6%);
    • Diabetes (8/36; 22.2%);
    • Hyperlipidemia (8/36; 22.2%);
    • Chronic kidney disease (8/36; 22.2%).
  • 16 (44.4%) of the patients were non-Hispanic Black and 12 (33.3%) were Hispanic/Latinx.
    • In the general clinic population, 50% are White, 30% Black and 10% Hispanic/Latinx.
  • 16 of 36 (44.4%) lived or worked in a congregate setting (group home, assisted living or skilled nursing facility).
  • 11 (30.6%) worked in frontline jobs, including home health care and retail/grocery stores, or had household members working in these positions.

Limitations:

  • Observational/descriptive study; bias is possible.
  • The paper reports both probable and confirmed cases).
  • May have underrepresented patients with mild disease, as COVID-19 testing was not widely available for low-acuity symptoms during the early epidemic.
  • Did not capture asymptomatic cases.

 

Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users (Charre, October 2020).

Overall, in this observational study of comparing COVID-19 incidence among PLWH and persons who use PrEP, and persons not living with HIV or not using PrEP, HIV status and PrEP use were not associated with difference in COVID-19 incidence rates. The study is limited by a lack of matching.

Patient population:

  • PLWH and PrEP users in a region in France.

Primary endpoint:

  • The attack rate of COVID-19 in PLWH and PrEP users, compared to the general population.

Key findings:

  • The attack rate in the persons without HIV and not taking PrEP was 0.24% (95% CI: 0.23–0.24%, n=1,397,909 adults).
  • The attack rate in PLWH was 0.31% (95% CI: 0.18–0.55%, n=3874) and in PrEP users was 0.38% (.23–0.64%, n=1675).
  • A corrected attack rate estimation, accounting for temporal increases in PCR tests performed in outside laboratories reflected in cases registered with the health department, was similar.
  • HIV status and PrEP use was not associated with COVID-19 detection in multivariate analysis.
    • The only associated factor was age (OR 1.01 per year [1.01–1.01%)]).

Limitations:

  • Only symptomatic persons and health care workers were offered SARS-CoV-2 PCR testing; asymptomatic cases were not included.
  • Single locale study; the findings may not be generalizable.
  • Observational; bias is possible.

 

Characteristics, Comorbidities and Outcomes in a Multicenter Registry of Patients with HIV and Coronavirus Disease-19 (Dandachi, October 2020).

Overall, in this observational study of outcomes in PLWH and COVID-19, overall half of patients were hospitalized, and 16% required ICU stay. The overall mortality rates in persons admitted, and in the ICU, were relatively high. The study is limited by the lack of a comparator group.

Patient population:

  • A registry consisting of 286 consecutively, non-randomly enrolled PLWH with PCR-confirmed COVID-19 from 286 33 U.S. institutions and 3 non-U.S. institutions.
  • Mean age was 51.4 years (SD, 14.4).
  • 9% were female, and 75.4% were African-American or Hispanic.
  • Most patients (94.3%) were on ART, 88.7% had HIV virologic suppression and 80.8% had comorbidities.

Primary endpoint:

  • Severe outcome, defined as a composite endpoint of intensive care unit (ICU) admission, mechanical ventilation or death.

Key findings:

  • 164 (57.3%) patients were hospitalized, and 47 (16.5%) required ICU admission.
  • Mortality rates were 9.4% (27/286) overall, 16.5% (27/164) among those hospitalized and 51.5% (24/47) among those admitted to an ICU.
  • Older age, CD4 <200, chronic kidney disease and chronic lung disease were significant predictors for hospitalization.
  • Older age, CD4 <200, chronic lung disease, hypertension and 3 or more comorbidities were significant predictors for a combined severe outcome of ICU admission, mechanical ventilation, or death.

Limitations:

  • COVID-19 testing, treatment and hospitalization were all done at the discretion of individual healthcare providers and may have varied widely between sites and time point in pandemic.
  • Death was counted as all-cause mortality; did not verify the exact cause of death.

 

Epidemiological, virological and serological features of COVID-19 cases in people living with HIV in Wuhan City: A population-based cohort study (Huang, August 2020).

Overall, in this large observational study of COVID-19 among PLWH in Wuhan, China, people who were older and not on ART had higher rates of COVID-19 incidence than those who did not. The study is limited by a lack of a comparator group.

Study population:

  • 6001 PLWH in Wuhan City, of whom 35 developed COVID-19.

Primary endpoint:

  • The cumulative incidence of COVID-19 in PLWH in the designated time period in Wuhan City compared to the incidence in the general population.

Key findings:

  • 58% of 6,001 PLWH in Wuhan, China, acquired COVID-19 (confirmed or probable) by April 16, 2020, compared to 0.45% in the general population (95% CI: 0.42-0.81).
    • Of the cases, 62.9% were confirmed, and 31.4% were diagnosed clinically
    • 86% of cases had severe illness and 5.71% were asymptomatic.
  • COVID-19 incidence among PLWH aged ≥50 years was 1.18%, which was higher than that of PLWH below 50 years (0.35%, IRR of 3.37 [95% CI: 1.73-6.57, p<0.001]).
  • COVID-19 incidence was 0.52% (95% CI: 0.36-0.76), 2.20% (95% CI: 0.82%-5.86%) and 0.63% (95% CI: 0.20%-1.96%) in PLWH with ART continuation, PLWH with ART discontinuation and PLWH without ART, respectively.
  • The mean duration of viral RNA shedding among confirmed COVID-19 cases in PLWH was 30 (IQR: 20-46) days. In the general population it was 20 days.
  • PLWH who acquired COVID and who were detectable (viral load >20 copies/mL) had lower IgM and IgG levels than those who were virologically suppressed (<20 copies/mL; median signal/cut off (S/CO) for IgM, 0.03 vs. 0.11, p<0.001; median S/CO for IgG, 10.16 vs. 17.0, p=0.069).
  • Compared to PLWH aged below 50 years with ART continuation, PLWH aged 50 years or above with ART discontinuation were at increased risk for COVID-19 (IRR=16.86, 95% CI: 4.71-60.26).

Limitations:

  • Retrospective observational study; bias is possible.
  • Small sample of patients with COVID-19 and HIV in which to examine secondary endpoints.
  • Cases of COVID-19 were not all confirmed.
  • Complete data on viral load and CD4 count was not available for all patients.



Factors associated with hospital admission for COVID-19 in HIV patients (Di Biago, August 2020).

Overall, in this observational health network study of PLWH in Italy, 3% of all patients in the network were diagnosed with COVID-19, and approximately 50% were admitted to a hospital. Of these patients, having a lower median CD4 lymphocyte count was associated with death, and 16% of admitted patients died. The study is limited by a lack of a comparator group and a lack of evaluation of the impact of comorbidities.

Patient population:

  • 22,000 PLWH within a network of health centers in Italy, of whom 69 had confirmed SARS-CoV-2.

Primary endpoint:

  • Descriptive study of the epidemiological, clinical features and outcomes of HIV patients with SARS-CoV-2.

Key findings:

  • Between February and March, of the 22,000 patients in the network, 69 (3%) were diagnosed with COVID-19.
  • 33 of the 69 patients were admitted; of these 3 were only admitted due to an inability to isolate at home.
  • The sex and age aORs for nadir CD4+ cells was 0.83 [by 50 cells/μl, 95% CI: 0.72–0.96] and 0.87 for lymphocytes count (by 100 cells/μl, 95% CI: 0.78–0.97).
  • Among those who were admitted to hospital, lower median lymphocyte count was associated with death (700 versus 1530, p=0.033).
    • The median hospital stay length was 12 days (range 1–33).
  • 10% of patients who acquired COVID-19 died, while 16% of the admitted patients died.

Limitations:

  • Small patient population.
  • The study was observational; there is risk for bias and the findings may not be generalizable.
  • Did not evaluate risks associated with medical comorbidities or social determinants of health.



Description of COVID-19 in HIV-infected individuals: a single-center, prospective cohort (Vizcarra, August 2020).

Overall, in this observational prospective cohort of PLWH in Spain, the incidence of COVID-19 in PLWH was not different from persons not living with HIV. The study is limited by a lack of matching, being single center, and because nearly a third of patients included did not have confirmed COVID-19.

Patient population:

  • 2,873 adult PLWH followed at a single health center in Spain.
  • The mean age was 53.3 years (SD 9.5); 43 (84%) were men.

Primary endpoint:

  • SARS-CoV-2 infection rate and clinical characteristics of COVID-19 among adults living with HIV.

Key findings:

  • The incidence of COVID-19 among PLWH was 1.8% (51 people).
    • 28 (55%) required hospital admission.
  • The incidence of confirmed COVID-19 with PLWH was similar to that of the general population (1.2% vs. 0.96%).
  • The incidence of confirmed and suspected COVID-19 in PLWH was lower than that of the general population (1.8% vs. 4.02%).
  • Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those without COVID-19.
  • 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0.00059).
  • 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0.0036).
  • 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0.578).
  • Six (12%) individuals were critically ill, two of whom had CD4 counts <200 cells/; two (4%) died.
  • SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in 6 (32%) individuals; 4 had severe disease or a low nadir CD4 count.

Limitations:

  • Only 69% of the cohort were confirmed cases.
  • Single center study; the findings may not be generalizable.
  • Observational; bias is possible.

 

 

Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa (Boulle, August 2020).

Overall, in this large observational study of PLWH in South Africa, HIV status was associated with increased mortality, as was current or prior tuberculosis infection. Some comorbidities were controlled for (diabetes, hypertension, chronic kidney disease and chronic pulmonary disease), but BMI, cardiac disease, etc., were not. Results may not be generalizable to areas with low rates of tuberculosis.

Patient population:

  • Population-based cohort study in South Africa using de-identified public sector health data from the Western Cape from over 3.4 million people, with 22,308 PCR-confirmed COVID-19 cases.
    • Approximately 520,000 PLWH live in the Western Cape.

Primary endpoint:

  • Comparison of the standard mortality ratio for COVID-19 between PLWH and persons without HIV.

Key findings:

  • Among 3,460,932 persons (16% HIV positive) who sought out public health sector services between March-June 2020, 22,308 were diagnosed with COVID-19.
    • 625 patients with COVID-19 died.
  • COVID-19 death was associated with male sex, increasing age, diabetes, hypertension and chronic kidney disease.
  • HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR] 2.14; 95% CI: 1.70-2.70), with similar risks across strata of viral load and immunosuppression. 
  • Current and previous tuberculosis were associated with COVID-19 death (aHR [95%CI] 2.70 [1.81-4.04] and 1.51 [1.18-1.93] respectively).
  • A greater proportion of COVID-19 deaths in PLWH occurred in persons <50 years (39%) compared to COVID-19 deaths in persons without HIV (13%).
  • There was an increased risk of death in PLWH hospitalized with COVID-19 as CD4 count decreased, compared to HIV-negative persons (CD4 >350: aHR 1.24, 95% CI: 0.95-1.63; CD4 200-349: aHR 1.65, 95% CI: 0.94- 2.88; CD4<200: aHR 2.36, 95% CI: 1.47-3.78).
  • PLWH receiving tenofovir-containing ART regimens had a lower risk of COVID-19 death compared to persons receiving abacavir or ziodovudine based regimens (aHR 0.41, 95% CI: 0.21-0.78, p=0.007), adjusting for age, sex and certain comorbidities. There was no difference when comparing to other ART regimens.

Limitations:

  • Relatively large numbers of PLWH had no recent viral load or CD4 count results, limiting the ability to distinguish outcomes for different strata of these measures.
  • Of patients who did have viral load data available, the majority were suppressed; it is possible if more patients with uncontrolled HIV were included the findings would be different.
  • Observational study; bias is possible.
  • The tenofovir and outcomes relationship may be confounded by indication, with persons receiving non-tenofovir ART more likely to do so as a result of concomitant renal disease or other unadjusted comorbidities. 

 

COVID-19 in Hospitalized Adults with HIV (Stoeckle, August 2020).

Overall, in this small matched observational cohort of PLWH who were hospitalized with COVID-19, there was no difference in lymphocyte counts, inflammatory markers or hospital outcomes between PLWH and those without HIV. Upon presentation more PLWH required oxygen. The study is limited by a small sample size.

Patient population:

  • 30 PLWH who were hospitalized with COVID-19 in New York City were matched to 90 persons without HIV by age, sex and race/ethnicity.
  • The median age was 60.5 (IQR 56.6–70.0 years).
  • 20% were female, 30% were black, 27% were white and 24% were of Hispanic/Latinx ethnicity.

Primary endpoint:

  • A comparison of respiratory status and other hospital events between PLWH and matched controls.

Key findings:

  • PLWH were more likely to smoke, have hepatitis B infection and have chronic obstructive pulmonary disease (COPD), but had similar cardiovascular comorbidities, frequency of diabetes and BMI compared to hospitalized COVID-19 cases without HIV.
  • All but one PLWH was on ART, and the mean CD4 was 332 (123–526) cells/μL.
  • Similar lymphocyte counts were seen between the groups.
  • Inflammatory markers between the groups were similar, except a trend toward lower C-reactive protein in PLWH.
  • There was no difference in hospital outcomes (ICU admission, ventilation, length of stay, death).
  • Upon presentation, more patients without HIV required a higher level of supplemental oxygen than PLWH.

Limitations:

  • The sample size was small.
  • The PLWH group appeared less ill based upon their lower levels of oxygenation/ventilation support required on admission.
  • The majority of PLWH were on ART and virally suppressed, which may limit the generalizability of these findings to persons with uncontrolled HIV or advanced disease.

 

Outcomes among HIV-positive patients hospitalized with COVID-19 (Karmen-Tuohy, June 2020).

Overall, in this small matched observational study of PLWH with COVID-19 in New York City, and persons not living with HIV and COVID-19, PLWH had higher inflammatory markers. However, hospital based outcomes, including length of stay and mortality, were not different between the groups. The study is limited by a small sample size. 

Patient population:

  • 21 PLWH with COVID-19 who were admitted March 2-April 23, 2020 were matched with 42 persons without HIV and COVID-19 in New York City.
    • Matching was performed on admission date, age, gender and comorbidities.
  • All PLWH were on antiretroviral therapy prior to admission; of the 19 people in whom viral load data was available, 17 were suppressed.
  • The median CD4 count was 298 (IQR 135-542).

Primary endpoint:

  • A comparison of admission characteristics, laboratory test results and hospital outcomes between PLWH and matched controls.

Key findings:

  • Admission and peak C-reactive protein values differed between groups, with median values (IQR) consistently higher in PLWH vs. non-HIV COVID cases (HIV+ baseline 154.48 ± 94.44 vs. non-HIV: 96.1 ± 90.0, P value: 0.020; HIV+: 185.13 ± 107.35 vs. non-HIV: 128.06 ± 99.29, P value: 0.024).
  • Length of hospital stay, proportion requiring intensive care or mechanical ventilation, and mortality were not statistically significantly different between the groups.
  • There was a non-statistically significant trend towards higher ICU admission (28.6% vs. 16.7%), mechanical ventilation (23.8% vs. 11.9%) and mortality (28.6% vs. 23.8%) among PLWH vs. non-HIV COVID patients.

Limitations:

  • This was a retrospective study that is susceptible to confounding variables.
  • The small sample size prevented detection of small differences among groups.
  • The majority of PLWH were on ART and virally suppressed, which may limit the generalizability of these findings to persons with uncontrolled HIV or advanced disease.

 

Clinical Outcomes and Immunologic Characteristics of Coronavirus Disease 2019 in People with Human Immunodeficiency Virus (Ho, June 2020).

Overall, in this large randomized controlled trial of patients admitted to hospitals in China with COVID-19,  lopinavir/ritonavir did not reduce mortality or time to clinical improvement. The majority of patients in the study received lopinavir/ritonavir in their second week of illness, which may be too late for  lopinavir/ritonavir to have an effect.

Patient population:

  • Retrospective case series of 93 PLWH in New York City who presented to emergency departments between March 2-April 15, 2020 and were found to have COVID-19.

Primary endpoint:

  • To characterize the clinical course of PLWH who develop COVID-19.

Key findings:

  • The median age was 58 years (IQR, 52–65 years).
  • Median duration of HIV infection was 20 years (IQR, 15–26 years) and nadir CD4+ T-cell count was 320 cells/μL (IQR, 139–490 cells/μL).
  • 72 (77.4%) patients were admitted to the hospital; 19 (26.4%) admitted patients required ICU-level care, 15 (20.8%) requiring mechanical ventilation, and 19 (26%) died.
  • In 30 patients with CD4+ data from the past year, a substantial decline in median CD4 count at admission was seen (464 vs. 188 cells/μL; p<.0001); similarly a decline in absolute lymphocyte count at the time of COVID-19 diagnosis was seen in persons with previous data available (1.9 vs. 0.9 × 103 cells/μL; p<.0001).
  • Low absolute nadir lymphocyte count was associated with mortality.
  • Inflammatory markers including CRP, IL-6 and IL-8 were significantly higher among subsets of those who died compared with those who recovered.
  • There was no statistically significant difference in the proportion of COVID-19 deaths in persons receiving tenofovir-based vs. non-tenofovir-containing ART (73.6% vs. 55.5%, p=0.15).

Limitations:

  • Retrospective study conducted in single center.
  • There was no comparison group of HIV-negative persons.
  • The majority of patients were on ART and virally suppressed, which may limit the generalizability of these findings to persons with uncontrolled HIV or advanced disease.

 

Additional Literature

Clinical characteristics, risk factors, and incidence of symptomatic coronavirus disease 2019 in a large cohort of adults living with HIV: a single-center, prospective observational study (Inciarte, October 2020). In this prospective observational single-center cohort study of adult PLWH reporting symptoms of COVID-19 in Barcelona, clinical characteristics, risk factors for COVID-19 diagnosis and severity and standardized incidence rate ratio for COVID-19 cases were assessed. Fifty-three out of 5,683 PLWH were diagnosed with COVID-19. The median absolute CD4 count was 618/μl, and only 2 people were not suppressed. Forty-nine percent of patients were admitted, 14% had severe disease, 8% required ICU admission and 4% died. No HIV or antiretroviral-related factors were associated with COVID-19 diagnosis or severity.

Clinical characteristics, comorbidities and outcomes among persons with HIV hospitalized with coronavirus disease 2019 in Atlanta, Georgia (Collins, October 2020). In this case series of all PLWH sequentially admitted with COVID-19 from March 8, 2020 to April 23, 2020 at three hospitals in Atlanta, sociodemographic, clinical and HIV-associated characteristics were assessed. Of 530 confirmed COVID-19 cases hospitalized during this period, 20 occurred among PLWH (3.8%). The median age was 57 (Q1–Q3, 48–62) years, and 85% were non-Hispanic Black. Presenting median symptom duration was 5 (Q1–Q3, 3–7) days. Forty percent of patients required oxygenation support and 65% had an abnormal chest radiograph. Median length of hospitalization was 5 (Q1–Q3, 4–12) days, 30% required intensive care, 15% required intubation and 15% died. Median CD4+ cell count prior to admission was 425 (Q1–Q3, 262–815) cells/μl and 90% of patients had HIV-1 RNA less than 200 copies/mL. Half of the patients had at least five comorbidities. All three patients who died had CD4 cell count >200, HIV suppression and each had a total of five comorbidities.

Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users (Charre, October 2020). In this retrospective observational study of persons using  tenofovir-based PrEP and PLWH in France, the positivity rate was similar in PLWH (15.6%), PrEP users (14.8%) and in other patients (19.1%). The crude/corrected COVID-19 attack rate appeared similar in PLWH (0.31/0.38%) and in PrEP users (0.38/0.42%) and of the same order as the estimated attack rate in the general population (0.24%). Of note, this study is limited by the testing strategy at the time, which tested symptomatic and hospitalized persons only, and few tests performed on persons using PrEP (N=27).

Epidemiological, Virological and Serological Features of Coronavirus Disease 2019 (COVID-19) Cases in People Living With Human Immunodeficiency Virus in Wuhan: A Population-based Cohort Study (Huang, August 2020). In this population-based cohort study of all COVID-19 cases among all PLWH in Wuhan, China, by April 2020, epidemiological, virological and serological features were analyzed. The cumulative incidence of COVID-19 among PLWH was 0.58%. Fifteen (42.86%) had severe illness, with 2 deaths. The incidence, case-severity and case-fatality rates of COVID-19 in PLWH were comparable to those in the entire population in Wuhan. The median duration of SARS-CoV-2 viral shedding was 30 days (IQR, 20–46). Cases with high HIV viral loads (≥20 copies/mL) had lower IgM and IgG levels than those with low HIV viral loads (<20 copies/mL; median signal value divided by the cutoff value [S/CO] for IgM, 0.03 vs. 0.11, respectively [p<.001]; median S/CO for IgG, 10.16 vs. 17.04, respectively [p=0.069]).

COVID-19 and People with HIV Infection: Outcomes for Hospitalized Patients in New York City (Sigel, June 2020). In this matched cohort study in New York City comparing PLWH with COVID-19 to persons without HIV and COVID-19, clinical characteristics and outcomes were assessed. PLWH hospitalized with COVID-19 had high proportions of viral suppression on ART. PLWH had greater proportions of smoking (p<.001) and comorbid illness. There was no difference in COVID-19 severity on admission by HIV status (p=.15). Poor outcomes for hospitalized PLWH were similar to those in controls; 18% required mechanical ventilation and 21% died during follow-up (compared with 23% and 20%, respectively). There was similar cumulative incidence of death over time by HIV status (p=.94).

Clinical Characteristics and Outcomes in People Living with Human Immunodeficiency Virus Hospitalized for Coronavirus Disease 2019 (Shalev, May 2020). Description of clinical characteristics of 31 PLWH hospitalized for SARS-CoV-2 in New York. The mean age was 60.7 years (range, 23–89 years); 24 (77%) were men. Seventy percent had one or more high-risk non-HIV comorbidity. All were on ART and all had suppressed viral load. Disease severity was distributed as follows: mild, 1 patient (3.2%); moderate, 2 (6.5%); severe, 21 (67.7%); and critical, 7 (22.6%). All 8 deaths were in persons >50 (4) or >65 (4).

Clinical features and outcomes of HIV patients with coronavirus disease 2019 (Gervasoni, May 2020). Retrospective descriptive study of 47 PLWH in Italy with confirmed or probable COVID-19 between February 21-April 16, 2020. The majority were male (76%), mean age was 51 (SD 11) years, 64% had at least 1 comorbidity and all were receiving ART. Of the study population, 44 (94%) had undetectable HIV viral loads, the other 3 had VL<200 copies/mL. Thirteen (28%) were hospitalized, 2 required mechanical ventilation and 2 died. Mean age of PLWH with COVID-19 was approximately 10 years lower than in HIV-negative patients with COVID-19. Risk of death and ICU admission were lower in PLWH than in persons without HIV treated in the same hospital.

Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy (Del Amo, June 2020). In this cohort study of all PLWH with COVID-19 attending 6 HIV clinics in Spain, the risk of hospitalization was 20.3 (95% CI: 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 ( 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI: 17.2 to 31.1) among those receiving ABC/3TC and 20.0 (CI: 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI: 31.8 to 47.6), 16.9 (CI: 10.5 to 25.9), 28.3 (CI: 21.5 to 36.7) and 29.7 (CI: 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died. The major limitation of this study is that in places where TAF is widely available in 2019 and 2020, TDF may be disproportionately prescribed for persons without chronic kidney disease or others at high risk of it (age, diabetes, hypertension — all also risk factors of COVID-19). Because this study did not adjust for comorbidities, it is possible that confounding by indication (lack of comorbidities) accounts for the reported “protective” effect of TDF.

Description of COVID-19 in HIV-infected individuals: a single-center, prospective cohort (Vizcarra, May 2020). In this observational prospective study of all consecutive PLWH admitted to a hospital in Spain who had suspected or confirmed COVID-19 as of April 30, 2020, 37 (73%) patients had received TDF/TAF before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0.0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0.578). ART containing tenofovir (almost exclusively TAF) was associated with an OR of 3.7 for COVID-19 compared to non-tenofovir regimens after adjustment for comorbidities and obesity.

Triple combination of interferon beta-1b, lopinavir-ritonavir and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomized, phase 2 trial (Hung, May 2020). In this phase 2 randomized controlled trial examining a triple combination therapy of interferon beta-1b, lopinavir/ritonavir and ribavirin, the combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5–11]) than the control group (12 days [8–15]; hazard ratio 4.37 [95% C: 1.86–10.24], p=0.0010). The median number of days from symptom onset to start of study treatment was 5 days (IQR 3–7).

 

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