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  52nd ICAAC Interscience Conference on
Antimicrobial Agents and Chemotherapy
September 9-12, 2012, San Francisco
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Pneumococcal Disease Risk 30 Times Higher With Than Without HIV in Denmark
  52nd ICAAC, September 9-12, 2012, San Francisco

Poorly Controlled HIV Infection Raises Risk of Pneumococcal Disease in French Study - Written by Mark Mascolini - (09/09/12)

Mark Mascolini

HIV-positive people in Denmark run almost a 30 times higher risk of invasive pneumococcal disease (IPD) than HIV-negative people, according to results of a nationwide study [1]. IPD risk declined after the year 2000, while a low CD4 count raised the risk.

Incidence of IPD (bacteremia, meningitis, or infection of other normally sterile sites [2]) is more than 100 times higher in HIV-positive people than in the general population. US CDC guidelines say "HIV-infected adults and adolescents who have a CD4+ count of greater than 200 cells/uL should be administered a single dose of 23-valent polysaccharide pneumococcal vaccine (PPV23) unless they have received this vaccine during the previous 5 years" [3]. But many countries, including Denmark, don't have HIV-specific recommendations for PPV vaccination.

Danish researchers planned this nationwide population-based case-control study to define IPD incidence in HIV-positive and negative people in Denmark, and to identify risk factors. The analysis involved all HIV-positive people older than 15 seen at all Danish HIV treatment centers from 1995 through 2007. For each HIV-positive person, the researchers identified 19 HIV-negative controls matched to the HIV "cases" by age and gender.

Among the 4944 people with HIV there were 110 IPD diagnoses (2.2%), compared with 83 among 93,955 HIV-negative controls (0.009%) (P < 0.001). Age at IPD diagnosis was significantly younger in the HIV group (40 versus 50 years, P < 0.001), but 30-day IPD mortality was lower in the HIV group (7% versus 25%, P = 0.01). HIV infection boosted the risk of IPD more than 30 times (adjusted incidence rate ratio [aIRR] 31, 95% confidence interval (CI) 23 to 41, P < 0.001).

IPD risk dropped sharply from about 750 cases per 100,000 person years in 1995-1996 (before wide use of combination antiretroviral therapy), to about 500 per 100,000 in the early years of combination therapy (1997-1999) to less than 500 per 100,000 in 2000-2007. In 1995-1996 IPD incidence was 47 times higher in people with HIV than in HIV-negative people; in 1997-1998 IPD incidence was 42 times higher in the HIV group; and in 2000-2007 IPD incidence was still 26 times higher in people with HIV.

Besides HIV infection, the researchers identified three other predictors of IPD. Being 65 or older (compared with 16 to 39) almost quadrupled the risk (aIRR 3.8, 95% CI 2.2 to 6.5, P < 0.001). Follow-up in the early combination ART era (1997-1999) boosted the IPD risk 50% (aIRR 1.5, 95% CI 1.4 to 1.5, P < 0.001), and follow-up in the precombination era (1995-1996) more than doubled the risk (aIRR 2.4, 95% CI 1.5 to 3.9, P < 0.001).

Looking only at people with HIV, the researchers found that a lower proportion with than without IPD were men (66% versus 76%, P < 0.001), and a higher proportion with than without IPD were injection drug users (26% versus 11%, P < 0.001). Nadir CD4 count was significantly lower in HIV-positive people diagnosed with IPD (87 versus 150, P < 0.001). In multivariate analysis limited to HIV-positive people, injection drug use tripled the risk of IPD, a CD4 count of 100 to 349 versus 350 or higher more than doubled the risk, and a CD4 count below 100 versus 350 or higher upped the risk more than 8 times.

Compared with HIV-negative people, the HIV-positive group had a quadrupled risk of recurrent IPD (IRR 4.3, 95% CI 2.9 to 6.7, P < 0.001). Of the 10 cases of recurrent IPD in people with HIV, 6 occurred in people with a CD4 count below 200 and 1 in a person with an unknown CD4 count. Seven of 10 people with recurrent IPD were taking antiretroviral therapy.

Another study of invasive pneumococcal disease at this meeting (reported separately by NATAP) identified several risk factors in a 2000-2001 case-control analysis in France: cumulative AIDS and non-AIDS conditions, a low CD4 count, a detectable viral load, and being born outside of France [4].


1. Harboe ZB, Larsen MV, Ladelund S, et al. Incidence and risk factors for invasive pneumococcal disease in HIV infected and uninfected individuals in Denmark. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-1916.

2. Centers for Disease Control and Prevention. Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 1997;46(No. RR-8):1-19. http://www.cdc.gov/mmwr/pdf/rr/rr4608.pdf.

3. Centers for Disease Control and Prevention. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents. MMWR. 2009;58(No. RR-4):1-216.

4. Munier A, de Lastours V, Porcher R, et al. Risk factors of invasive pneumococcal disease in HIV-infected patients in France from 2000-2011. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract H-219.