Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study

Vaccine. 2013 Nov 19;31(48):5745-53. doi: 10.1016/j.vaccine.2013.09.032. Epub 2013 Oct 1.

Abstract

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339.

Keywords: APC; ART; ATP; BARC; Bio Analytical Research Corporation; CI; ELISA; GMT; HIV; HPV; HPV vaccination; HPV-16/18 AS04-adjuvanted vaccine; Human immunodeficiency virus (HIV); Human papillomavirus (HPV); IDMC; Immunogenicity; Independent Data Monitoring Committee; MPL; NOCD; PMTCT; Preventing Mother-to-Child Transmission of HIV; SAE; Safety; TVC; WHO; World Health Organisation; according-to-protocol; antigen-presenting cell; antiretroviral therapy; confidence interval; enzyme-linked immunosorbent assay; geometric mean antibody titre; human immunodeficiency virus; human papillomavirus; monophosphoryl lipid A; new-onset chronic disease; serious adverse event; total vaccinated cohort.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adolescent
  • Adult
  • Aluminum Hydroxide / administration & dosage*
  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes / immunology
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • HIV / isolation & purification
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Human papillomavirus 16 / immunology
  • Human papillomavirus 18 / immunology
  • Humans
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives*
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / prevention & control*
  • Papillomavirus Infections / virology
  • Papillomavirus Vaccines / administration & dosage
  • Papillomavirus Vaccines / adverse effects*
  • Papillomavirus Vaccines / immunology*
  • Single-Blind Method
  • South Africa
  • Vaccination / adverse effects
  • Vaccination / methods
  • Viral Load
  • Young Adult

Substances

  • ASO4 mixture
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Lipid A
  • Papillomavirus Vaccines
  • human papillomavirus vaccine, L1 type 16, 18
  • Aluminum Hydroxide

Associated data

  • ClinicalTrials.gov/NCT00586339