Rates of pneumococcal disease remain high in patients with HIV

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Overall incidence of invasive pneumococcal disease is approximately 20 times higher in patients with HIV compared to the general population, according to UK research published in the online edition of AIDS. Even in patients with a CD4 cell count above 500 cells/mm3 rates of the disease were seven times higher than those seen in HIV-negative individuals.

Risk factors for invasive pneumococcal disease included older age, a low CD4 cell count and not taking HIV therapy. The researchers also found that a newer vaccine that is effective against 13 pneumococcal serotypes (PCV13) would provide greater levels of protection for patients with HIV than the vaccine currently in use.

“The risk of invasive pneumococcal disease among HIV-positive adults remains elevated compared to the general population even among those with higher CD4 and receiving antiretroviral therapy,” comment the researchers.

Glossary

pneumococcal disease

Disease caused by the bacterial infection Streptococcus pneumoniae. In most people, it causes relatively minor health problems (called ‘non-invasive’ infections) such as bronchitis, sinusitis (sinus inflammation) and middle-ear infections. It can also cause serious pneumococcal diseases including severe bacterial pneumonia, sepsis (blood poisoning) or meningitis (inflammation of the brain lining).

invasive

In medical terms, going inside the body.

adjusted odds ratio (AOR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

nadir

Lowest of a series of measurements. For example, an individual’s CD4 nadir is their lowest ever measured CD4 count.

matched

In a case-control study, a process to make the cases and the controls comparable with respect to extraneous factors. For example, each case is matched individually with a control subject on variables such as age, sex and HIV status. 

They recommend that a diagnosis of invasive pneumococcal disease in any adult aged 15-44 in the United Kingdom should trigger the offer of an HIV test, due to the elevated risk in people with HIV infection. Testing adults diagnosed with pneumococcal disease for HIV could help to identify people otherwise unaware of their HIV status.

Patients with HIV are especially susceptible to pneumococcal infection. The immune restoration that accompanies successful antiretroviral therapy can provide protection against pneumococcal disease. Studies conducted in the US have shown a decline in incidence of the disease since effective HIV treatment because available.

However, these studies involved patients with lower CD4 cell counts. Wider data on the incidence of invasive pneumococcal disease in HIV-infected individuals is lacking.

UK investigators therefore analysed the records of 63,109 adults who received HIV care between 2000 and 2009. They calculated the incidence of invasive pneumococcal disease in these patients which was then compared to the rates observed in the general population. Analyses were conducted to determine the risk factors for the disease.  The investigators also assessed the impact of PCV7 vaccination programmes on the prevalence of Streptococcus pneumoniae serotypes.

Overall, 951 patients developed invasive pneumococcal pneumonia in the period of analysis. The disease recurred in 43 (5%) of individuals. A fifth of patients had an AIDS diagnosis and 13% had died by the end of 2009. The median time between the detection of the disease and death was 178 days, but 28% of deaths occurred within the first month after diagnosis.

A total of 136 individuals (14%) were unaware of their HIV status at the time pneumococcal disease was diagnosed.

“We suggest that the offer and recommendation of HIV tests should be adopted for adults aged 15-44 who present with invasive pneumococcal disease regardless of clinical presentation, especially where no other risk factors for IPD are found,” write the authors.

Average annual incidence of invasive pneumococcal disease was 245 cases per 100,000, approximately 20 times higher than that seen in the general UK population.

Incidence differed according to age and was 246 cases per 100,000 among patients aged 15 to 44, approximately 50 times higher than the rate observed in HIV-negative individuals, and 232 cases per 100,000 for patients aged between 45 and 64, some 25 times than the rate in the general UK population.

Rates of the disease were high in patients with a low CD4 cell count (below 200 cells/mm3 = 563 cases per 100,000 vs. 140 cases per 100,00 for individuals with a CD4 cell count above 200 cells/mm3; p < 0.001).

The highest incidence of the disease was seen in individuals with a low CD4 cell count who were not receiving HIV treatment (1,685 cases per 100,000).

Rates of invasive pneumococcal disease were significantly lower in patients taking antiretroviral therapy who had a CD4 cell count above 500 cells/mm3 (71 cases per 100,000; p < 0.001). Nevertheless, incidence of the disease was still almost seven times higher than the rate seen in the general population.

The 951 patients who developed the disease were matched with 3,804 HIV-positive controls without indentified invasive pneumococcal disease. Significant risk factors for the disease were older age – 65 years and above (adjusted odds ratio [aOR] = 3.53; 95% CI, 1.55-8.04); a CD4 cell count nadir below 200 cells/mm3 and between 201-349 cells/mm3 (aOR = 2.61; 95% 1.85-3.70 and aOR = 1.77; 95% CI, 1.30-2.41 respectively); and not taking HIV therapy (aOR = 8.40; 95% CI, 6.75-14).

“Our study underscores the importance of early HIV diagnosis and the protective effect of antiretroviral therapy on invasive pneumococcal disease co-infection,” comment the investigators.

In 2009 the proportion of disease episodes covered by the PCV7 vaccine was 23%. However, a much higher proportion of cases – 61% - were covered by the recently developed PCV13 vaccine.

“Our study provides evidence for policies regarding the use of the newly available PCV13 in HIV-positive adults for their direct protection,” note the authors.

References

Yin Z et al. Invasive pneumococcal disease among HIV-positive individuals in England and Wales, 2000-2009. AIDS 25, doi: 10. 1097/QAD.0b013e32834dcf27, 2011.