The incidence of invasive pneumococcal disease and community-acquired pneumonia remains high among people living with HIV, investigators from the Netherlands report in Clinical Infectious Diseases. Rates of these serious infections were highest among people not taking anti-HIV drugs and with CD4 cell count below 500. Incidence was also much higher than that seen in the general population. Dr Hannah Garcia Garrido and her colleagues at the University of Amsterdam Medical Centre believe their findings show the importance of providing the pneumococcal vaccine to all people with HIV.
“This highlights that even in a well-managed patient population in an academic HIV treatment centre in a high-income country, pneumococcal disease and community-acquired pneumonia remain important causes of morbidity,” comment the authors.
Background and methods
Pneumonia is an infection of the lungs that causes inflammation. The infecting organism may be bacteria, a virus (such as influenza), a fungus (such as Pneumocystis pneumonia or PCP) or something else. The disease is sometimes characterised by where the infection was acquired: in the community, in hospital or in a nursing home. This study looked at community-acquired pneumonia.
Pneumococcal disease refers to any disease caused by the bacterial infection Streptococcus pneumoniae. This includes pneumonia with that cause (sometimes called pneumococcal pneumonia). However, this study also looked at invasive pneumococcal disease, which refers to often serious infections such as bacteraemia, sepsis or meningitis.
A large body of research has shown that people living with HIV have an increased risk of pneumococcal disease, but much of this research was conducted either before combination therapy was introduced (in the mid-1990s) or in the early treatment era which relied on drugs that would now be considered sub-optimal. Moreover, since 2015, antiretrovirals have been recommended for all people with HIV, regardless of CD4 cell count.
Dr Garcia Garrido and her colleagues therefore wanted to see if people with HIV remained at increased risk of pneumococcal disease and community-acquired pneumonia in the modern treatment era. Their study involved people with HIV who received care at the University of Amsterdam’s HIV clinic between 2008 and 2017. They identified all cases of pneumococcal disease and community-acquired pneumonia and undertook a series of analyses to calculate incidence rates for both diseases. A case-controlled analysis was used to identify risk factors for community-acquired pneumonia.
Cases of pneumococcal disease and community acquired pneumonia were laboratory confirmed. Samples were analysed to determine the pneumococcal strain and the type of pathogen causing the community acquired pneumonia. The investigators especially wanted to see if strains were covered by pneumococcal vaccines. The use of this vaccine among people with HIV is recommended in international guidelines, though in the Netherlands it is only recommended for people with HIV who have additional risk factors. Despite longstanding recommendations, in all settings, vaccine uptake is low.
The investigators identified 24 cases of invasive pneumococcal disease (in 21 people living with HIV) and 318 episodes of community-acquired pneumonia (in 215 people living with HIV). There was a high mortality rate: 8% for invasive pneumococcal disease and 4% for community-acquired pneumonia.
Incidence rates of invasive pneumococcal disease, community-acquired pneumonia and pneumococcal community-acquired pneumonia were 111, 1529 and 159 per 100,000 person-years of follow-up, respectively.
Rates of invasive pneumococcal disease were higher among individuals who were not taking anti-HIV drugs (490/100,000) or who had a CD4 cell count below 500 (246/100,000) compared with people on antiretrovirals (80/100,000) or with a CD4 cell count above 500 (40/100,000).
Similarly, for community-acquired pneumonia, incidence was highest among those not on antiretrovirals and with a CD4 cell count below 500 (8023/100,000). Rates were much lower in people taking anti-HIV drugs and with a high CD4 cell count (946/100,000).
The investigators undertook a case-control analysis to determine the risk factors for community-acquired pneumonia among individuals on antiretrovirals. Each case was matched with a person diagnosed with HIV in the same year who did not develop pneumonia.
"The incidence of invasive pneumococcal disease among people with HIV was seven times higher than that seen in the general Dutch population."
Identified risk factors included age of 60 years and older, a CD4 cell count below 500, smoking, recreational drug use and chronic obstructive pulmonary disease. Coverage of pneumococcal vaccination was low in both the cases and controls (7% vs 4%).
The incidence of invasive pneumococcal disease among people with HIV was seven times higher than that seen in the general Dutch population and 20-times higher than that recorded among healthy individuals in the Netherlands. Similarly, incidence of community-acquired pneumonia among the HIV-positive individuals was eight times higher than that seen among the Dutch population as a whole.
Microbiological analysis showed that the pneumococcal vaccines covered all the cultured strains. Penicillin resistance was identified in 7% of Streptococcus pneumoniae cases, with one strain having resistance to multiple classes of antibiotics.
“With Streptococcus pneumoniae the most commonly identified pathogen of community acquired pneumonia, and all the serotyped pneumococcal isolates being covered by available pneumococcal vaccines, we provide additional arguments against the current poor adherence to international recommendations for pneumococcal vaccination,” conclude the authors.
Garcia Garrido HM et al. Incidence and risk factors for invasive pneumococcal disease and community-acquired pneumonia in human immunodeficiency virus-infected individuals in a high-income setting. Clinical Infectious Diseases, online ahead of print, 2019 (open access).
This article was updated on 27 November 2019 to include more background information.