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COVID-19 in patients with HIV: clinical case series
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April 15, 2020 HIV Lancet
Jose L Blanco, Juan Ambrosioni, Felipe Garcia, Esteban Martínez, Alex Soriano, Josep Mallolas,
*Jose M Miro, on behalf the COVID-19 in HIV Investigators
Download the PDF here
https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(20)30111-9/fulltext
As of March 24, 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected almost 400 000 people in 168 countries on five continents. Older patients (>60 years) and those with comorbidities (eg, hypertension, diabetes, cardiovascular disease, lung disease, and chronic kidney disease) present with more severe infection and worse prognosis. 1
Coronavirus disease 2019 (COVID-19) has been described in only one patient with HIV in Wuhan, China,2
but case series in patients with HIV are lacking despite 37·9 million people having HIV globally.3
Here we describe, to our knowledge, the first single-centre experience of COVID-19 in patients infected with HIV-1, including clinical characteristics, antiviral and antiretroviral treatment, and outcomes.
All patients gave informed consent for publishing their clinical data. We used nasopharyngeal swab samples for all diagnoses, amplifying the betacoronavirus E gene and the specific SARS-CoV-2 RdRp gene by PCR.
On March 9, 2020, 2 weeks into the COVID-19 outbreak in Spain, 543 consecutive patients with SARS-CoV-2 infection had been admitted to hospital at Hospital Clínic Barcelona, Barcelona, Spain. We admitted 62 (12%) into intensive care units and we discharged 208 (38%) with supervised outpatient care. Of all patients, five (0·92%; 95% 0·39–2·14) were HIV positive (table), of whom three were male and two were transgender, and four identified as men who have sex with men (MSM). Two patients had comorbid conditions. Two patients were sex workers. Four were virologically suppressed: two with protease-inhibitor (darunavir-boosted cobicistat) and two with integrase-inhibitor (dolutegravir)-based antiretroviral therapy (ART). CD4 counts were above 400 cells per μL in all patients apart from patient 5, who was ART naive and a very advanced late presenter. Two patients had upper-respiratory tract infections, and three had viral pneumonia, including two requiring admission to the intensive care unit with invasive (patient 2) and non-invasive (patient 5) mechanical ventilation.
Lopinavir-boosted ritonavir was given as 400 mg of ritonavir boosted with 100 mg of lopinavir twice a day for 14 days; azithromycin was given as 500 mg once a day, with a loading dose on the first day, and then 250 mg once a day for 4 days; hydroxychloroquine was given as 400 mg twice a day with a loading dose on the first day and then 200 mg twice a day for 4 days, and interferon beta-1b was given as 250 μg (8 million units) every 48 h. MSM=men who have sex with men. ND=Not done.
We started all five patients on anti-SARS-CoV-2 treatment on the day of diagnosis. We gave all five patients boosted-protease inhibitor ART. We explained to patients treated with ART that we were making a transitional change in their regimen on the basis of the fact that HIV protease inhibitors might have activity against the coronavirus protease and that once the treatment ended they would return to their usual regimen. Patient 1 with darunavir-boosted cobicistat, and patients 2–4 were adapted to lopinavir-boosted ritonavir. We gave patient 5 darunavir-boosted cobicistat. We left patient 1, who had mild infection, on his normal ART. We gave the other patients hydroxychloroquine (patients 2, 3, 4, and 5) with azithromycin (patients 3, 4, and 5), and interferon beta-1b (patient 2 and 5). No patients were given remdesivir (only available through clinical trials, with restricted access at the time these patients were evaluated). We administered concomitant antibacterials in all three patients who had pneumonia (patients 2, 4, and 5), and corticosteroids in two patients (patients 4 and 5) and tocilizumab in one (patient 2). We have discharged four patients (80%); one remains in hospital in the intensive care unit (patient 2).
Our preliminary experience highlights several issues. First, patients with HIV accounted for almost 1% of patients with COVID-19 who required admission to hospital in Barcelona.
We only observed the infection in people younger than 50 years, who identified as MSM, and who have a COVID-19 clinical pictures resembling the general population. None of these five patients has died, although we admitted two to intensive care, where one remains. More studies of COVID-19 in patients with HIV are needed in the older MSM population, drug users, and heterosexual men and women in middle-income and lower-income settings. Second, two patients who were MSM were sex workers, one reporting participating in a chemsex party 6 days before admission to hospital. During this pandemic, implementing health education programmes is very important to explain that such activities as these could cause clusters of SARS-CoV-2 transmission. Third, we adapted ART in all patients to a regimen based on protease inhibitors: three patients were given lopinavir-boosted ritonavir and two were given darunavir-boosted cobicistat. In the past month, a clinical trial4 found that lopinavir-boosted ritonavir was ineffective as a monotherapy against severe pneumonia associated with COVID-19 in China. Therefore, investigation of the efficacy of this treatment in patients with COVID-19 in combined therapy in earlier stages of the disease is needed. Additionally, Janssen reported on March 18, 2020, that darunavir was ineffective against SARS-CoV-2 due to low affinity to coronavirus protease. Fourth, we did not give our patients remdesivir, the most active in-vitro and in-vivo antiviral drug against coronavirus to date,5
and is currently only available through clinical trials or for compassionate use. This drug has no pharmacokinetic interactions with any medication including ART drugs. Finally, in advanced patients (ie, late presenters), we must ensure differential diagnosis and initial antimicrobial treatment to address pulmonary opportunistic infections (eg, Pneumocystis jirovecii, as seen in patient 5) presenting with similar clinical and radiological symptoms. This pandemic is a challenge affecting everyone. By generating information such as we present here, the management and prognosis of patients co-infected with HIV and SARS-CoV-2 might be improved.
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