Incidence and Risk Factors for Invasive Pneumococcal Disease and Community-acquired Pneumonia in Human Immunodeficiency Virus–Infected Individuals in a High-income Setting

Abstract

Background Although people living with human immunodeficiency virus (PLWH) are at increased risk of invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP), it is unclear whether this remains the case in the setting of early initiation of combination antiretroviral therapy (cART), at high CD4 cell counts. This is important, as pneumococcal vaccination coverage in PLWH is low in Europe and the United States, despite longstanding international recommendations. Methods We identified all CAP and IPD cases between 2008 and 2017 in a cohort of PLWH in a Dutch HIV referral center. We calculated incidence rates stratified by CD4 count and cART status and conducted a case-control study to identify risk factors for CAP in PLWH receiving cART. Results Incidence rates of IPD and CAP in PLWH were 111 and 1529 per 100 000 patient-years of follow-up (PYFU). Although IPD and CAP occurred more frequently in patients with CD4 counts <500 cells/μL (incidence rate ratio [IRR], 6.1 [95% confidence interval, 2.2–17] and IRR, 2.4 [95% confidence interval, 1.9–3.0]), the incidence rate in patients with CD4 counts >500 cells/μL remained higher compared with the general population (946 vs 188 per 100 000 PYFU). All IPD isolates were vaccine serotypes. Risk factors for CAP were older age, CD4 counts <500 cells/μL, smoking, drug use, and chronic obstructive pulmonary disease. Conclusions The incidence of IPD and CAP among PLWH remains higher compared with the general population, even in those who are virally suppressed and have high CD4 counts. With all serotyped IPD isolates covered by pneumococcal vaccines, our study provides additional argumentation against the poor current adherence to international recommendations to vaccinate PLWH.

The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation

“…As these cells are known to be highly permissive to HIV infection and serve as reservoirs during chronic infection, they could potentially explain these disrupted B/T cell interactions (64)(65)(66). Clinically, compromised B/T cells interactions may contribute to impaired immune responses to vaccination as well as increased risks for infections, such as invasive pneumococcal disease (5,67). Finally, improvement of B/T cell communication is crucial for the development of broadly neutralizing antibodies and thus functional cure in PLHIV (68).…”

“…Combination antiretroviral therapy (cART) has drastically curtailed morbidity and mortality in people living with HIV (PLHIV) (1). Still, PLHIV remain at an increased risk for pneumococcal infections, Mycobacterium tuberculosis (M. tuberculosis) reactivation and impaired vaccine responses (2)(3)(4)(5)(6). Moreover, HIV infection predisposes to non-infectious comorbidities, such as cardiovascular disease and non-AIDSrelated cancer, which share an underlying pathophysiological pathway characterized by a persisting and inappropriate activation of innate and adaptive immune cells (7,8).…”

Immunogenicity of pneumococcal vaccination in HIV infected individuals: A systematic review and meta-analysis

“…The durability of the immune response following pneumococcal vaccination is an important issue, even more so as life expectancy of PLWH under cART has nowadays approximated that of HIV-negative counterparts. In addition, the risk of pneumococcal infections increases at more advanced age [1] . With respect to the durability of the immune response, PCV is often thought to be superior, because PPSV23 does not induce immunologic memory [5 , 65] .…”

“…People living with HIV (PLWH) are at increased risk of pneumococcal disease, even in the era of advanced combination antiretroviral therapy (cART). A recent study showed an incidence rate of pneumococcal disease in PLWH of 190 per 100,000 patient-years of follow-up, compared to 38 per 100,000 in the general population [1] . Pneumococcal disease in PLWH often requires hospitalisation, and mortality rates range up to 25% [2].…”

Underutilised human immunodeficiency virus testing in the setting of invasive pneumococcal disease

“…People living with human immunodeficiency virus (HIV) are at an increased risk of invasive pneumococcal disease (IPD), 1–3 being at least seven times more likely to develop IPD, independent of other known risk factors 4 or CD4 count, 2 resulting in significant mortality and morbidity. In addition, IPD may be the first presentation to healthcare for people living with HIV, 5,6 providing an opportunity for earlier diagnosis of HIV.…”