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Phase I/II, Open-Label Trial of Safety and Immunogenicity of Meningococcal (Groups A, C, Y, and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine in Human Immunodeficiency Virus-Infected Adolescents

Siberry, George K. MD, MPH*; Williams, Paige L. PhD; Lujan-Zilbermann, Jorge MD; Warshaw, Meredith G. MSS, MA; Spector, Stephen A. MD§; Decker, Michael D. MD, MPH; Heckman, Barbara E. BS; Demske, Emily F. BA**; Read, Jennifer S. MD, MS, MPH, DTM&H*; Jean-Philippe, Patrick MD††; Kabat, William BS‡‡; Nachman, Sharon MD§§the IMPAACT P1065 Protocol Team

The Pediatric Infectious Disease Journal: May 2010 - Volume 29 - Issue 5 - p 391-396
doi: 10.1097/INF.0b013e3181c38f3b
Original Studies

Background: Quadrivalent meningococcal polysaccharide conjugate vaccine (MCV4) is routinely recommended for healthy youth in the United States, but there are no data about its use in HIV-infected people.

Methods: P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network. All youth (11–24 years old) received 1 dose of open-label MCV4 at entry. Standardized questionnaires were used to evaluate safety. Baseline protective immunity was defined as rabbit serum bactericidal antibody (rSBA) titer ≥1:128. Immunogenic response was defined as a ≥4-fold rise in rSBA against each meningococcal serogroup. Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C.

Results: Among 319 subjects who received MCV4, 10 (3.1%) reported immediate adverse events which were local and mild, and 7 (2.2%) experienced Grade ≥3 adverse events, unrelated to vaccine. The 305 subjects with serologic data had a median age of 17 years and were 59% male, 50% Black, and 38% Latino. Subjects were stratified by entry CD4%: 12%, CD4 <15%; 40%, 15% to 24%; and 48%, ≥25%. Baseline protective immunity varied by serogroup: A, 41%; C, 11%; W-135, 15%; Y, 35% The immunogenic response rates to serogroups A, C, W-135, and Y were 68%, 52%, 73%, and 63%, respectively. In multivariable logistic regression models, lower entry CD4%, higher entry viral load, and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C.

Conclusion: Many HIV-infected youth naturally acquire meningococcal immunity. MCV4 is safe and immunogenic in HIV-infected youth, but response rates are lower than in healthy youth, particularly for those with more advanced HIV clinical, immunologic, and virologic status.


From the *Pediatric, Adolescent, and Maternal AIDS Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; †Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA; ‡Division of Infectious Diseases, Department of Pediatrics, University of South Florida College of Medicine, Tampa, FL; §Department of Pediatrics, Division of Infectious Diseases, University of California, San Diego, and Rady Children's Hospital San Diego, La Jolla, CA; ¶Sanofi Pasteur Inc., Swiftwater, PA, and Department of Preventive Medicine, Vanderbilt University, Nashville, TN; ∥Frontier Science and Technology Research Foundation, Amherst, NY; **Social and Scientific Systems, Inc, Silver Spring, MD; ††Henry Jackson Foundation for the Advancement of Military Medicine, National Institute of Allergy and Infectious Diseases, Division of AIDS, Bethesda, MD; ‡‡Special Infectious Disease Laboratory, Divisions of Infectious Disease and Pathology, The Children's Memorial Hospital, Chicago, IL; and §§Department of Pediatrics, SUNY Stony Brook, Stony Brook, NY.

Accepted for publication September 29, 2009.

Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by the National Institute of Allergy and Infectious Diseases (NIAID) the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9–001/HHSN267200800001C). Additional support for this work was provided with Federal funds from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200800014C. Sanofi-Pasteur Inc. provided study vaccine and performed meningococcal serum bactericidal antibody activity assays.

M.D.D. is an employee of Sanofi-Pasteur, manufacturer of the vaccine evaluated in this study. S.A.S. holds stock in Sanofi-Pasteur, manufacturer of the vaccine evaluated in this study. There are no additional financial disclosures. There are no additional conflicts of interest to report.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Address for correspondence: George K. Siberry, MD, MPH, Pediatric, Adolescent, and Maternal AIDS (PAMA) Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6100 Executive Boulevard, Room 4B11H, Bethesda, MD 20892–7510. E-mail:

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