Is HIV a fragile virus
Georg Härter, Ulm
HIV and COVID-19 - Current Status
Issue 2 - 2020
So far, there is very little data worldwide on the course of COVID-19 in HIV infection. A new case series from Germany shows no relevant increased mortality.
In December 2019, an accumulation of pneumonia of unknown cause was noticed in the city of Wuhan in China. A coronavirus was identified as the cause (Zhu N, 2020). In the meantime, the virus has been named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease as COVID-19 (Lu 2020, Zhu N, 2020). The WHO has classified the SARS-CoV-2 infection as a global pandemic and according to the current status (May 19, 2020), 4,696,849 infected people and 315,131 deaths are reported in 216 countries worldwide (WHO 2020).
So far, the data on COVID-19 infections in high prevalence countries for HIV (e.g. Africa) are only sparse (WHO 2020). With the increasing number of infections, however, it is to be feared that SARS-CoV-2 infections will also increase significantly in HIV-infected people. Especially in countries with fragile health systems and inadequate basic medical care, severe disease and numerous deaths among people infected with HIV must be expected.
In larger case series, risk factors for a serious course of a COVID-19 infection are above all older age, male gender, obesity and existing underlying diseases, including above all D. mellitus and arterial hypertension as well as COPD or chronic kidney diseases and a history of malignant disease ( Richardson 2020; Grasselli 2020; Liang 2020).
People infected with HIV now have a normal life expectancy. As a result, HIV patients are more likely to reach old age. Many HIV patients, especially those who have been infected for a longer period of time, have a statistically significantly higher percentage of comorbidities such as chronic kidney disease, COPD or diabetes mellitus (Gueraldi 2018). This may result in an increased risk of a more severe course of a COVID-19 infection.
For coronaviruses, including severe acute respiratory syndrome (SARS) -CoV and SARS-CoV-2, it has been shown that there is a temporary immune dysfunction with a decrease in the absolute CD4 cell count (Chen 2020, He 2005, Quin 2020). It is currently unclear whether this temporary immunosuppression is relevant for people infected with HIV.
Previous study results on other respiratory viruses (e.g. pandemic influenza) show that HIV-infected people who receive antiretroviral therapy do not have any increased morbidity and mortality (Peters 2011, Lynfield 2014).
So far there is no reliable evidence that an infection with SARS-CoV-2 or an illness from it (COVID-19) is more severe in HIV-infected people than in non-infected people. This is accepted by the various specialist societies, at least under the prerequisite of a well-controlled HIV infection with suppressed HIV-RNA and a good immune status under antiretroviral therapy (joint statement of the German AIDS Society, the European AIDS Society (EACS), the BHIVA, GESIDA & Polish Scientific AIDS Society; Statement from the US Public Health Authority (DHHS)).
In a large cohort study from the UK, 1% of patients with comorbidities out of 16,749 hospitalized COVID-19 patients were HIV positive (Docherty 2020). However, details of the clinical course in HIV-infected people are not apparent from this. In addition to individual case reports (Wu 2020, Zhu F 2020, Louisa 2020), there are currently five “larger” case series in the literature. A report from Spain with five patients (Blanco 2020), from China with 8 cases with confirmed HIV and COVID-19 infection (Guo 2020), from Germany with 33 cases (Härter 2020), from Italy (Gervasoni 2020) with 47 patients (28 confirmed) and from the USA with 21 cases (Karmen-Tuohy 2020). The last three studies mentioned are examined in more detail below.
The symptoms most frequently mentioned in Germany for COVID-19 infections in the general population were cough (49%), fever (41%) and runny nose (21%) (RKI 2020). In the case series from Germany (Härter 2020), the symptoms mentioned were comparable: cough in 78%, fever in 69%, arthralgias / myalgias as well as headaches and pharyngitic complaints in 22% each. Sinusitis and odor or taste disorders were observed in 19% each. In the study from Italy, fever (87%), cough (49%) and dyspnoea (21%) were the most frequently mentioned symptoms (Gervasoni 2020). In summary, the symptoms were comparable to larger cohorts (RKI, 2020; Zhou F 2020).
The somewhat younger age of those infected with HIV compared to larger cohorts was striking: in the German case series, the mean age was 48 years (Härter 2020) and in Italy 51 years (Gervasoni 2020), whereas in a large cohort study of hospitalized patients in New York, the median age was 63 years (Richardson 2020). One explanation here could be the overall younger age in HIV cohorts, but also country-specific differences; the median age of confirmed cases in Germany is only 49 years (RKI 2020).
In the larger case series, a high percentage of comorbidities was recorded: 60% (Härter 2020) and 64% (Gervasoni 2020). This is in line with the overall higher rates of comorbidities among people infected with HIV (Gueraldi 2018).
In the case series from Germany, the outcome is documented in 32 patients. 29/32 (91%) recovered from COVID-19 at the last follow-up. 76% were classified as mild. Nevertheless, 24% were severe or critical cases. The hospitalization rate was 42% higher than in the general population in Germany with 17% (RKI 2020). In Italy, too, the hospitalization rate was 46% higher than in the general population (Gervasoni 2020). The number of patients who required intensive medical treatment, at 43% of the hospitalized patients (Härter et al., 2020) and 29% (Karmen-Tuohy 2020), was higher than in comparison with large cohort studies (14%) (Ri-chardson 2020) or 28% (Petrilli 2020). However, the hospitalization rate for SARS-CoV-2 infections cannot be specified precisely, since an estimated 20-40% of infections are asymptomatic (Gudbjartsson 2020; Mizumoto 2020). It is therefore possible that the hospitalization rate for HIV-infected people is overestimated in the case series because only symptomatic patients or only hospitalized patients are described. Another “bias” could lie in the fact that HIV-infected patients were more likely to be admitted to the hospital for observation due to the classification as possible risk patients.
A total of three patients died (9%) (Härter et al., 2020). This means a case fatality rate of 9% and thus appears at first glance to be higher than in the entire German population of 4.6% (RKI 2020). However, the mortality of the hospitalized patients with 3/14 (21%) (Härter 2020) is comparable to the mortality of the HIV case series from New York with 29% (Karmen-Tuohy 2020). The large cohort analyzes from China and the USA show similar mortality rates among hospitalized patients of 28% (Zhou F 2020) and 21% (Richardson 2020). Thus, there is no relevant increased mortality among the hospitalized HIV-infected people with COVID-19.
Effect of ART
There may be a protective effect from the antiretroviral therapy. In particular, the HIV protease inhibitors (PI) such as lopinavir and darunavir are attributed a certain effect in the context of the current epidemic, but the data are not uniform.
Lopinavir appears to have antiviral effects against both MERS-CoV and SARS-CoV and to inhibit a post-entry step in the replication cycle (de Wilde 2020). The first larger, well-controlled and openly randomized study of lopinavir / ritonavir in 199 hospitalized adults with severe COVID-19 disease showed no relevant clinical benefit versus standard therapy (Cao 2020).
A large study (CQ4COV19) with over 3,000 participants started on March 18 in Spain for the protease inhibitor darunavir. Patients with mild symptoms are treated with darunavir / r and chloroquine immediately after a positive SARS-CoV-2 test. However, on March 13, the manufacturer Janssen-Cilag published a letter to the EMA, according to which “Darunavir will probably not have any significant activity against SARS-CoV based on preliminary, unpublished results of an in vitro experiment - when administered in the approved dose for the treatment of HIV- 1 infections. ”Even a small case series from Italy showed no relevant benefit from darunavir / ritonavir (Riva 2020). In our case series (Härter et al., 2020), too, four patients were treated with a darunavir-containing regimen before the COVID-19 disease, 3/4 had to be hospitalized and one patient died. In the Italian case series, 5/47 (10%) were treated with a boosted protease inhibitor (Gervasoni 2020). This makes a protective effect of the protease inhibitors unlikely.
In addition to the protease inhibitors, a potential effect against SARS-CoV-2 is also postulated for tenofovir. The nucleoside analogue remdesivir shares some chemical similarities with tenofovir alafenamide (TAF). Tenofovir possibly binds to the SARS-CoV-2 RNA polymerase (RdRp) (Elfiky 2020; Jockusch 2020, Ju J 2020). A large, randomized, placebo-controlled study on prophylaxis against COVID-19 health workers is currently ongoing in Spain. Tenofovir disoproxil / emtricitabine is compared with hydroxychloroquine or the combination versus placebo (EPICOS).
The clinical course of COVID-19 in HIV-infected people is similar to the general population.
Overall, a relevant increase in mortality cannot be observed.
Antiretroviral therapy does not seem to have a protective effect. Therefore, switching to a protease inhibitor, for example, is not justified. The use of TDF / FTC as PrEP outside of the existing indication as HIV prophylaxis cannot be recommended either.
Regular clinical care for people infected with HIV must be maintained even in times of pandemic.
Dr. med. Georg Härter, Medicover Ulm
Münsterplatz 6 89073 Ulm
Email: [email protected]
Literature from the author
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