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Pneumococcal conjugate vaccination in persons with HIV: the effect of highly active antiretroviral therapy

Søgaard, Ole Sa; Schønheyder, Henrik Cb; Bukh, Anne Ra; Harboe, Zitta Bc; Rasmussen, Thomas Aa; Østergaard, Larsa; Lohse, Nicolaia

doi: 10.1097/QAD.0b013e328339fe0b
Clinical Science

Objective: Vaccination responses may be affected by concomitant use of highly active antiretroviral therapy (HAART). We aimed to determine HAART's impact on seven-valent pneumococcal conjugate (7vPnC) vaccine immunization with or without a Toll-like receptor 9 (TLR9) agonist adjuvant.

Design: Observational cohort study.

Methods: Adults with HIV were immunized with double doses of 7vPnC ±1 mg CPG 7909, a TLR9 agonist and vaccine adjuvant, at 0 and 3 months, and 23-valent pneumococcal polysaccharide vaccine at 9 months. We measured IgG levels (ELISA) and opsonophagocytic activity (OPA) at months 0, 3, 4, 9, and 10. Persistent 7vPnC vaccine responders were defined as individuals with two-fold IgG increases to 1 μg/ml or more for at least five of the 7vPnC serotypes at 9 months.

Results: We included 75 participants on HAART and 20 HAART-naive. Forty-one received CPG 7909 and 48 received placebo adjuvant. More persistent 7vPnC vaccine responders were found among HAART-treated than among HAART-naive (42.3 vs. 15.0%, P = 0.03). Mean loss of vaccine-specific IgG from month 4 to 9 was greater among HAART-naive than among HAART-treated (54.8 vs. 38.1%, P = 0.001). Functional activity (OPA) was higher among HAART-treated than among HAART-naive at 4, 9, and 10 months. In a logistic regression analysis (adjusted for baseline CD4+ cell count, CPG 7909, smoking status, BMI, AIDS diagnosis, and age), HAART use was significantly associated with being persistent 7vPnC vaccine responder at month 9 [odds ratio = 4.65, 95% confidence interval (CI) 1.07–20.2].

Conclusions: HIV-infected adults on HAART achieved a more durable antibody response of higher functional activity following pneumococcal conjugate vaccination than HAART-naive individuals, independently of baseline CD4+ cell count.

aDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark

bDepartment of Clinical Microbiology, Aarhus University Hospital, Aalborg, Denmark

cDepartment of Bacteriology, Mycology and Parasitology, Statens Serum Institut, Copenhagen, Denmark.

Received 30 December, 2009

Revised 12 March, 2010

Accepted 16 March, 2010

Correspondence to Ole S. Søgaard, MD, Department of Infectious Diseases, Aarhus University Hospital, Skejby Brendstrupgaardvej 100, 8200 Aarhus N, Denmark. Tel: +45 8949 8492; fax: +45 8949 8490; e-mail:

© 2010 Lippincott Williams & Wilkins, Inc.