HIV-positive patients still at high risk of pneumococcal infections in the HAART era

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The incidence of pneumococcal disease in HIV-positive patients remains elevated in the HAART era, according to Spanish research published in the June 1st edition of Clinical Infectious Diseases, which is now available on-line. What’s more, the investigators found that pneumococcal disease was as likely to occur in patients with a CD4 cell count above 200 cells/mm3 as it was in individuals with a CD4 cell count below this level, and that mortality caused by pneumococcal infections was high.

A variety of infections caused by the bacterium Streptococcus pneumoniae are termed pneumococcal illnesses. The most common types of pneumococcal infection include pneumonia and meningitis. There was an elevated incidence of pneumococcal infections in HIV-positive individuals in the pre-HAART era.

As trends in the incidence of pneumococcal infections since the advent of HAART had not been properly defined, investigators from Barcelona conducted a study looking at all HIV-positive patients treated at their hospital for invasive pneumococcal infections between 1996 and 2002.

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).

antibiotics

Antibiotics, also known as antibacterials, are medications that destroy or slow down the growth of bacteria. They are used to treat diseases caused by bacteria.

invasive

In medical terms, going inside the body.

pneumonia

Any lung infection that causes inflammation. The infecting organism may be bacteria (such as Streptococcus pneumoniae), 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.

sensitivity

When using a diagnostic test, the probability that a person who does have a medical condition will receive the correct test result (i.e. positive). 

The investigators set out to determine the incidence of infections, the influence of CD4 cell count on presentation, severity and outcome of the infection, and the value of preventative antibiotic prophylaxis. Data were collected retrospectively until 2000 and prospectively from 2000 onwards.

Between 1996 and 2002, a total of 467 episodes of invasive pneumococcal disease were identified at the investigators’ centre. In total,. 70 (15% of all cases) episodes occurred in 57 HIV-positive individuals. The incidence rate in HIV-positive patients was 677 cases per 100,000 patient years of follow-up, 60 times greater than the incidence in HIV-negative patients (11.3 cases per 100,000 patient years of follow-up).

A little over half (54.3%) of pneumococcal infections in HIV-positive individuals occurred when a patient had a CD4 cell count below 200 cells/mm3. A total of 32 cases (45.7%) involved patients whose CD4 cell count was above 200 cells/mm3, and seven of these cases involved patients whose CD4 cell count was above 500 cells/mm3.

HAART was being used by patients involved in 33% of the pneumococcal episodes, and a further 12 episodes occurred when a patient was taking antiretroviral therapy involving less than three drugs. In 50% of episodes, the pneumococcal disease developed when the patient was taking no anti-HIV treatments.

A little over half of the cases (52%) involved strains that were highly susceptible to penicillin, 41% of cases had intermediate penicillin sensitivity, and 7% were highly resistant to penicillin.

It did not matter if a patient’s CD4 cell count was above or below 200 cells/mm3: clinical presentation, severity, rates of antibiotic resistance and mortality (21%) were the same.

In 30 of the episodes, the patient was taking prophylactic antibiotic treatment against pneumococcal infection, consisting of trimethoprim-sulfamethoxazole (TMP-SMZ). There was no difference in the incidence rate of infections according to the use of prophylaxis. Nor did the use of prophylaxis have any influence on the severity of disease or mortality rates. Patients who received prophylaxis were, however, significantly more likely to have resistance to TMP-SMZ antibiotics.

The investigators comment that even though the incidence of certain other AIDS-related opportunistic infections has declined markedly in their centre since the introduction of HAART, “the number of cases of invasive pneumococcal infections has remained stable.”

They discuss possible reasons why the incidence has remained unchanged, even with the introduction of HAART, and note that several other immune factors, other than CD4 cell count, are involved in pneumococcal infection. These include IgA levels, mononuclear cells, and humoral host responses. What’s more, they note that only 33% of patients with pneumococcal infections were taking HAART, and that large numbers of patients were taking either suboptimal anti-HIV therapy or no anti-HIV treatment at all. They speculate that “it is possible that the incidence of pneumococcal disease would have been decreased if only patients receiving HAART had been analysed.”

Risk factors for pneumococcal infections include injecting drug use, and the investigators note that there was a high prevalence of intravenous drug users in their cohort.

Given the high mortality associated with pneumococcal infection, the investigators conclude that in areas with a high incidence of the infection, “pneumococcal vaccine should be offered to HIV-infected patients until new data on its efficacy is available.”

Further information on this website

Bacterial infections - overview

Immunisations - factsheet

References

Jordano Q et al. Invasive pneumococcal disease in patients infected with HIV: still a threat in the era of highly active antiretroviral therapy. Clinical Infectious Diseases 38 (on-line edition), 2004.