In this prospective cohort study the investigators will assess the prevalence and incidence of a broad range of age-related co-morbidities and their (known) risk factor among HIV-patients and HIV-negative controls. HIV might cause premature onset or accelerated aging and could therefore result in an increase of age-related comorbidities when compared with controls.

The standard use of combination antiretroviral therapy (cART) has resulted in major and sustained declines in HIV-associated morbidity and mortality. Nonetheless, the life expectancy of patients with HIV on cART still remains 10 or more years shorter than that of uninfected persons of the same age, especially in patients starting cART at the time infection is already advanced. A greater risk of a broad range of co-morbidities, experienced by as many as 60% of patients, even after adjustment for age, may contribute to this discrepancy. Several studies have demonstrated an increased incidence of heart disease, diabetes mellitus, kidney disease, liver disease, osteoporosis, malignancies (other than Kaposi's sarcoma and non-Hodgkin's lymphoma traditionally associated with HIV), cognitive disorders and possibly chronic obstructive pulmonary disease in HIV-infected individuals when compared to age matched HIV-uninfected controls. Of note, the incidence of each of the mentioned co-morbidities is also higher after adjustment for age and other traditional risk factors. Most studies were conducted in the United States where prevalence of and risk factors for the various co-morbidities may be different than in Europe, in particular the Netherlands.

HIV-related factors and adverse effects of cART each may independently contribute to the observed increased risk of several of the earlier mentioned co-morbidities. Interestingly, HIV-infected men in the absence of cART have increased frailty (a clinical syndrome associated with aging that identifies a subset of older adults at high risk of mortality and other adverse outcomes) when compared to uninfected men of similar age. Middle aged HIV-infected men despite cART use also show reduction in exercise capacity, functional performance, physical activity, and grip strength.

The multidisciplinary expertise regarding co-morbidities which is present within the AMC in close collaboration with the existing data collection structures of the HIV Monitoring Foundation (HMF) and the Cluster of Infectious Diseases of the Public Health Service Amsterdam (PHSA), offers a unique opportunity to systematically identify the burden of co-morbidity, their (known) risk factors and their effect on quality of life among HIV-infected individuals and in a comparable group of uninfected individuals.

As of August 2020, the study was amended to include a substudy, the main aim of which is to determine and compare the rate of SARS-CoV-2 infection, the extent of the SARS-CoV-2-specific adaptive immune response, and the incidence and severity of COVID-19 disease between PWH and HIV-negative cohort participants who remain in active follow-up.

Furthermore, if disease prevalence is sufficiently high, another aim will be to determine and compare risk factors for the development of severe COVID-19 between PWH and HIV-negative controls. Furthermore, an attempt will be made to compare the impact of nationally imposed social distancing measures on substance use, medication adherence, sexual behavior, quality of life and depressive symptoms in study participants.

Specific aims

1. To assess the SARS-CoV-2 infection rate in HIV-positive and -negative participants over 24 months by combined testing for in vivo SARS-CoV-2 specific antibodies, and in vitro SARS-CoV-2 specific memory B-cell and T-cell responses.
2. To assess the course over time of SARS-CoV-2 specific antibody levels, the quantity of SARS-CoV-2-specific memory B-cell, as well as CD4 and CD8 T-cell responses, and the functionality of the overall T cell response in vitro in HIV-positive and -negative participants with demonstrated SARS-CoV-2 infection, as well as the presence of SARS-CoV-2 cross-reactive common cold coronavirus (HKU1, OC43, NL63 and 229E) specific CD4 and CD8 T-cell responses in selected participants.
3. To assess the proportion of HIV-positive and -negative participants who carried broadly recognizing coronavirus (HKU1, OC43, NL63 and 229E) antibodies, prior to demonstrated SARS-CoV-2 infection.
4. To assess the rate and severity of COVID-19 disease in HIV-positive and -negative participants.
5. To assess factors associated with SARS-CoV-2 infection, development of COVID-19 and severe disease (i.e. requiring hospitalization and/or ICU-admission) in HIV-positive and HIV-negative participants.
6. To assess associations between nationally imposed social distancing measures and substance use, medication adherence, social behavior, quality of life and depression in study participants.

Inclusion Criteria:

• For the HIV-positive patients: HIV-1 infection and aged 45 years and above
• For the HIV-negative controls: HIV-uninfected and aged 45 years and above

Exclusion Criteria:

• None

The HIV-positive patients are recruited at the HIV outpatient clinic of the Academic Medical Center The HIV-negative controls are recruited at the STD-clinic of the Public Health Service Amsterdam and at the existing Amsterdam Cohort Studies.