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Safety, Reactogenicity, and Immunogenicity of Human Rotavirus Vaccine RIX4414 in Human Immunodeficiency Virus-positive Infants in South Africa

Steele, Andrew Duncan PhD*†; Madhi, Shabir Ahmed MD, PhD‡; Louw, Cheryl Emily MB ChB§; Bos, Pieter NHD†; Tumbo, John M. MB ChB, MFamMed¶; Werner, Corne M. MB ChB§; Bicer, Ceyhun MS∥; De Vos, Beatrice MD**; Delem, Andree MSc**; Han, Htay Htay MB BS**

Pediatric Infectious Disease Journal: February 2011 - Volume 30 - Issue 2 - pp 125-130
doi: 10.1097/INF.0b013e3181f42db9
Original Studies

Background: Rotavirus and human immunodeficiency virus (HIV) infections are a cause of great public health concern in developing countries. The current study evaluated the safety, reactogenicity, and immunogenicity of RIX4414 vaccine in asymptomatic or mildly symptomatic (clinical stages I and II according to WHO classification) HIV-infected South African infants.

Methods: A total of 100 HIV-positive infants aged 6 to 10 weeks enrolled in this double-blind, 1:1 randomized, placebo-controlled study were allocated into 2 groups to receive 3 doses of RIX4414 vaccine/placebo according to a 0-, 1-, and 2-month schedule. Routine vaccines were concomitantly administered. Solicited and unsolicited symptoms were recorded for 15 and 31 days after each dose, respectively. Serious adverse events were recorded throughout the study period. Serum antirotavirus IgA concentrations (enzyme-linked immunosorbent assay, cut-off ≥20 U/mL) and the immunodeficiency status were determined at screening and 2 months post-Dose 3. Stool samples were analyzed for rotavirus using enzyme-linked immunosorbent assay at predetermined points and during diarrhea episodes.

Results: All symptoms (solicited and unsolicited) occurred at a similar frequency in both groups. Six fatal serious adverse events in RIX4414 and 9 in placebo groups were reported. At 2 months post-Dose 3, the seroconversion rates were 57.1% (95% CI: 34–78.2) in RIX4414 and 18.2% (95% CI: 5.2–40.3) in the placebo group. The mean absolute CD4+ cell count, CD4+ percentage, and HIV-1 viral load were comparable in both groups at screening and 2 months post-Dose 3. Rotavirus shedding peaked at Day 7 after Dose 1 of RIX4414 with prolonged shedding was observed in 1 infant only.

Conclusions: Three doses of RIX4414 vaccine was tolerated well by the South African HIV-positive infants. A satisfactory immune response was mounted without aggravating their immunologic or HIV condition.

From the *Initiative for Vaccine Research, Department of Immunization, Vaccines and Biologicals, WHO, Geneva, Switzerland; †MRC Diarrheal Pathogens Research Unit, University of Limpopo, Pretoria, South Africa; ‡Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of Witwatersrand, Johannesburg, South Africa; §MCR (Madibeng Centre for Research), Brits, South Africa; ¶Department of Family Medicine, University of Limpopo, Pretoria, South Africa; ∥BICER Consulting & Research, Antwerp, Belgium; and **GSK Biologicals, Rixensart, Belgium.

Accepted for publication July 27, 2010.

Supported by research grants from the World Health Organization (V27/181/173), the Program for Appropriate Technology in Health (PATH Grant GAV.1142–01–07211-SPS), the Norwegian Program for Development, Research and Higher Education research grant (PRO 48/2002), and the South African Medical Research Council. GlaxoSmithKline Biologicals was also the funding source and was involved in all stages of the study conduct and analysis. GSK Biologicals also took in charge all costs associated with the development and the publishing of the present manuscript.

Beatrice De Vos is currently at University of Antwerp, Antwerp, Belgium.

Rotarix, Tritanrix, and PolioSabin are trademarks of GlaxoSmithKline group of companies.

Address for correspondence: Duncan Steele, M Med, PhD, Rotavirus Vaccine Program, PATH, PO Box 900922, Seattle, WA 98109. E-mail: dsteele@path.org.

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© 2011 Lippincott Williams & Wilkins, Inc.