The challenging of HIV care 1 year after of coronavirus disease 2019 pandemic: results from a Brazilian cohort.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by SARS-Cov-2 has not only caused a direct morbidity and years of life lost but also an indirect impact on chronic diseases, even on high-income countries [1]. Once the continuum care of chronic disease during the pandemic period becomes closely related to the availability of technological resources, people with HIV/AIDS in middle-income or low-income countries are at high risk of treatment interruption [2]. In addition, even in high-income countries, there is difficulty in maintaining the viral suppression, mostly in patients living in a precarious scenario (i.e. marginalized population) [3]. Thus, in spite of being a postcombination antiretroviral therapy (cART) era, some of the patients are back living in a pre-cART era, and consequently there are more hospital admissions with respect to AIDS-related conditions with a lower lymphocyte CD4+ count [4]. Considering this hypothesis, we evaluate the impact of COVID-19 on treatment of people with HIV/AIDS and patients under pre-exposure prophylaxis (PrEP) in a Brazilian public HIV care clinic. This was a cross-sectional analysis from a public adult HIV care clinic in Curitiba, Brazil, in which 5300 patients are registered and regularly collect cART or PrEP. Cross-sectional period was from March 2019 to February 2021. Prepandemic period was defined as March 2019 to February 2020 (first COVID-19-confirmed case was identified in Brazil on 25 February, 2020); postpandemic period was defined as March 2020 to February 2021. The folowing variables were analyzed: number of patients who attended to collect antiretrovirals, cART scheme collection frequency, new patients registered to HIV treatment and PrEP, latent tuberculosis treatment, and cART switch because of adverse reactions. The number of COVID-19 locally reported cases was also collected from the Municipal Health Department (https://coronavirus.curitiba.pr.gov.br/painelcovid/) and COVID-19 Data Repository by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (https://github.com/CSSEGISandData/COVID-19). Categorical and continuous variables were analyzed using a chi-squared test and Mann–Whitney U tests, respectively. Pearson correlation was performed to evaluate the number of COVID-19 cases and the variables collected. Significance was set at P less than 0.05, and IBM SPSS v.22 statistical software was used (IBM Corp., Armonk, New York, USA). In the prepandemic and postpandemic period, there was a median [IQR] of 4924 [4674–5239] and 4819 [4076–5181] ART collection was analyzed per month (P = 0.41). However, if the correlation between COVID-19 incidence and ART collection was analyzed, only the combination dolutegravir did not present modification, R = −0.1 (P = 0.77). Moderate correlation was found between COVID-19 incidence and darunavir/ritonavir-based therapy collection R = −0.47 (P = 0.0014) (Fig. 1). A strong correlation was found between COVID-19 incidence and efavirenz-based therapy, and atazanavir/ritonavir-based therapy, R = −0.602 (P = 0.001) and R = −0.698 (P < 0.001) (Fig. 1). In addition to the impact on ART collection, a moderate correlation was found between COVID-19 incidence and new registered patients at the HIV clinic, R = −0.4 (P = 0.0037), and a strong correlation was found between COVID-19 incidence and cART switch because of adverse effects, and latent tuberculosis treatment, R = −0.63 (P < 0.001) and R = −0.78 (P < 0.001), respectively (Fig. 2). In spite of some variation in patients under PrEP, there was no correlation with COVID-19 incidence, R = −0.3 (P = 0.1).Fig. 1: Combination antiretroviral therapy collection per month and coronavirus disease 2019 incidence between January 2019 and December 2020 – TDF+3TC+EFZ, ATZ/r- and DRV/r-based therapy. TDF, tenofovir; 3TC, lamivudine; EFZ, efavirenz; ATZ/r, atazanavir plus ritonavir; DRV/r, darunavir plus ritonavir.Fig. 2: Number of patients with combination antiretroviral therapy switch because of adverse effects, under latent tuberculosis treatment, and coronavirus disease 2019 incidence between January 2019 and December 2020.In Brazil, zidovudine/lamivudine/efavirenz and zidovudine/lamivudine with lopinavir/ritonavir were largely used 10–15 years ago as the initial therapy. Further, zidovudine was substituted by tenofovir, and lopinavir was substituted by atazanavir as the initial therapy before 2018. After 2018, the preferential adult regimen is based on lamivudine/tenofovir/dolutegravir, whereas protease inhibitors were set as a salvage therapy. Our results demonstrated that the current preferential scheme (dolutegravir-based) was not correlated with COVID-19 incidence. However, cART schemes based on PIs (i.e. ATZ/r and DRV/r) presented at least a moderate correlation. This might be an issue considering that this population probably presented an earlier HIV/AIDS diagnosis than patients under tenofovir/lamivudine with dolutegravir or presents HIV resistance to the initial preferred regimen. Additionally, cART regimens based on protease inhibitors usually present more adverse effects. Considering the simultaneous lower rates of protease inhibitor collection and cART switch because of adverse effects, this specific population is at a high risk of cART abandon because of intolerant adverse effects. Thus, the indirect clinical consequences of COVID-19 incidence in patients living with HIV/AIDS depend upon the duration of the COVID-19 pandemic and the further lockdown frequencies. Vaccination is still an issue in Brazil, and there is no more economic subsidy to the population; therefore, there is a high probability that 2021 will repeat the second semester 2020 COVID-19 incidence. The scenario in which patients with HIV/AIDS live and the antiretroviral therapy interruption risks have been studied to further create a better treatment approach. In the COVID-19 pandemic, initial studies have demonstrated that cART interruption was closely related to a previous interruption, lockdown policy, and areas with difficulty of medical access [2]. However, this issue may present itself as a quite more complex situation according to COVID-19 pandemic prolongation. In the late-pandemic COVID-19, an increase of substances abuse (e.g. alcohol and illicit drugs) and psychological diseases has been demonstrated, both of which increase the risk of cART abandonment also and worsen quality of life [5,6]. Telemedicine has been successfully used to overcome COVID-19 lockdown's consequences in some regions [7]. Nevertheless, considering that racial and ethnic minorities, and advanced AIDS patients, demonstrated a high risk of cART interruption [8,9], with an increase of substance abuse, and that these groups also have difficulty in accessing technological resources, there is a need to correctly evaluate which population is suitable for telemedicine in order to not increase social disparities and marginalization [10,11]. Moreover, our results highlighted the strong correlation between COVID-19 incidence and latent tuberculosis treatment. In Brazil, Mantoux Test is frequently unavailable, whereas Interferon Gamma Release Assay (IGRA) tests are too expensive to be used in a public health policy. Therefore, Brazilian protocols have established that all patients living with HIV/AIDS with a lymphocyte count less than 350 cel/μl should receive latent tuberculosis treatment because of the high tuberculosis (TB) endemicity in our country. Consequently, this recommendation should rise latent tuberculosis treatment rates; nevertheless, the opposite was demonstrated in our results. Two possible reasons may explain this result. First, the patient's loss of follow-up during the pandemic, and, second, the resources, such as X-ray machines, are aimed at supporting patients with COVID-19. Therefore, there is an accumulation of patients on the X-ray waiting list to exclude active TB before beginning latent TB treatment. These findings may be a concern over further months and the cause of a rise on tuberculosis rate in patients living with HIV/AIDS. Our study presents limitations. First, clinical and social characteristics were not evaluated. Second, no telephone survey was conducted to evaluate the impact of COVID-19 on quality of life of patients registered in our HIV care clinic. Our results highlight that the COVID-19 pandemic has influenced the continuum care of people with HIV/AIDS (i.e. missed cART collection, lower cART switch because of adverse effects, and lower HIV/AIDS new diagnosis). Additionally, latent tuberculosis treatment has dramatically decreased and this was strongly related to COVID-19 incidence. The clinical consequences remain to be evaluated in further studies. Acknowledgements Conflicts of interest There are no conflicts of interest.