PMID- 23840618
OWN - NLM
STAT- MEDLINE
DCOM- 20140121
LR  - 20240222
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 6
DP  - 2013
TI  - Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naive 
      subjects gives comparable immunogenicity to one dose in ART+ subjects.
PG  - e67177
LID - 10.1371/journal.pone.0067177 [doi]
LID - e67177
AB  - Tuberculosis (TB) is a global public health problem exacerbated by the HIV 
      epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in 
      HIV-infected adults in Senegal. 24 patients were enrolled: Group 1ratio12, 
      antiretroviral therapy (ART) naive, adults, with CD4 counts >300 and HIV RNA load 
      <100,000 copies/ml. Group 2ratio12 adults, stable on ART, with CD4 counts >300, and 
      an undetectable HIV RNA load. Safety was evaluated by occurrence of local and 
      systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, 
      haematology and biochemistry. Immunogenicity was evaluated by ex-vivo 
      interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 
      0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. 
      There were no vaccine-related Serious Adverse Events (SAEs) or clinically 
      significant effects on HIV RNA load or CD4 count. In ART naive subjects, the 
      first MVA85A immunisation induced a significant immune response at 1 and 4 weeks 
      post-immunisation, which contracted to baseline by 12 weeks. Durability of 
      immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A 
      second dose of MVA85A at 12 months enhanced immunogenicity in ART naive subjects. 
      Subjects on ART had higher responses after the first vaccination compared with 
      ART naive subjects; responses were comparable after 2 immunisations. In 
      conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in 
      Senegal. A two dose regimen in ART naive subjects is comparable in immunogenicity 
      to a single dose in subjects on ART. Clinicaltrials.gov trial identifier 
      NCT00731471.
FAU - Dieye, Tandakha N
AU  - Dieye TN
AD  - Laboratoire de Bacteriolgie-Virologie, Centre Hospitalier Universitaire Le 
      Dantec, Dakar, Senegal.
FAU - Ndiaye, Birahim P
AU  - Ndiaye BP
FAU - Dieng, Alle B
AU  - Dieng AB
FAU - Fall, Marema
AU  - Fall M
FAU - Brittain, Nathaniel
AU  - Brittain N
FAU - Vermaak, Samantha
AU  - Vermaak S
FAU - Camara, Makhtar
AU  - Camara M
FAU - Diop-Ndiaye, Halimatou
AU  - Diop-Ndiaye H
FAU - Ngom-Gueye, Ndeye Fatou
AU  - Ngom-Gueye NF
FAU - Diaw, Papa A
AU  - Diaw PA
FAU - Toure-Kane, Coumba
AU  - Toure-Kane C
FAU - Sow, Papa S
AU  - Sow PS
FAU - Mboup, Souleymane
AU  - Mboup S
FAU - McShane, Helen
AU  - McShane H
LA  - eng
SI  - ClinicalTrials.gov/NCT00731471
GR  - Wellcome Trust/United Kingdom
GR  - 095780/Wellcome Trust/United Kingdom
GR  - 076943/Z/05/Z/WT_/Wellcome Trust/United Kingdom
PT  - Clinical Trial, Phase I
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130628
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Tuberculosis Vaccines)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
EIN - PLoS One. 2013;8(10). 
      doi:10.1371/annotation/67550546-cacf-4063-8d62-d165da14ca61. Britain, Nathaniel 
      [corrected to Brittain, Nathaniel]
MH  - Adult
MH  - Anti-HIV Agents/*therapeutic use
MH  - CD4 Lymphocyte Count
MH  - CD4-Positive T-Lymphocytes/immunology/metabolism
MH  - Cells, Cultured
MH  - Drug Therapy, Combination
MH  - Female
MH  - HIV Infections/drug therapy/*immunology
MH  - HIV-1/*immunology
MH  - Humans
MH  - Immunization, Secondary
MH  - Immunocompromised Host
MH  - Interferon-gamma/metabolism
MH  - Male
MH  - Middle Aged
MH  - Tuberculosis Vaccines/administration & dosage/*immunology
MH  - Tuberculosis, Pulmonary/immunology/*prevention & control
MH  - Young Adult
PMC - PMC3696007
COIS- Competing Interests: HMcS is an inventor on a patent for MVA85A and is a 
      shareholder in a Joint Venture, the Oxford Emergent Tuberculosis Consortium, 
      formed for the development of MVA85A. This does not alter the authors' adherence 
      to all the PLOS ONE policies on sharing data and materials.
EDAT- 2013/07/11 06:00
MHDA- 2014/01/22 06:00
PMCR- 2013/06/28
CRDT- 2013/07/11 06:00
PHST- 2013/02/27 00:00 [received]
PHST- 2013/05/15 00:00 [accepted]
PHST- 2013/07/11 06:00 [entrez]
PHST- 2013/07/11 06:00 [pubmed]
PHST- 2014/01/22 06:00 [medline]
PHST- 2013/06/28 00:00 [pmc-release]
AID - PONE-D-13-10398 [pii]
AID - 10.1371/journal.pone.0067177 [doi]
PST - epublish
SO  - PLoS One. 2013 Jun 28;8(6):e67177. doi: 10.1371/journal.pone.0067177. Print 2013.