Safety of live, attenuated oral vaccines in HIV-infected Zambian adults: oral vaccines in HIV.
BACKGROUND
Current recommendations are that HIV-infected persons should not be given live vaccines. We set out to assess potential toxicity of three live, attenuated oral vaccines (against rotavirus, typhoid and ETEC) in a phase 1 study.


METHODS
Two commercially available oral vaccines against rotavirus (Rotarix) and typhoid (Vivotif) and one candidate vaccine against Enterotoxigenic Escherichia coli (ACAM2017) were given to HIV seropositive (n=42) and HIV seronegative (n=59) adults. Gastrointestinal symptoms were sought actively by weekly interview up to 1 month of vaccination. In rotavirus vaccine recipients, intestinal biopsies were collected by endoscopy and evaluated for expression of IL-8 and pro-inflammatory cytokines.


RESULTS
No difference was observed between symptoms in HIV infected and HIV uninfected vaccinees, except for diarrhoea reported more than 7 days after the last dose of vaccine. If only diarrhoea episodes within 7 days of vaccination are included, diarrhoea was not more frequent in HIV seropositive than in HIV seronegative vaccinees (OR 6.7, 95% CI 1.2-67; P=0.09). However, if later episodes of diarrhoea are included, a significant increase in diarrhoea was demonstrated (OR 5.3, 95% CI 0.98-53; P=0.04). All episodes were mild and transient. IL-8 was slowly up-regulated over the week following vaccination (P=0.02), but IL-β, IFNγ or TNFα were not.


CONCLUSIONS
No evidence was found of adverse events following administration of these three vaccines, except for late episodes of diarrhoea which may not be attributable to vaccination. Our data do not support the need for a prohibition on oral administration of live, attenuated vaccines to all HIV infected adults, though further work on severely immunocompromised adults and children are required.
Tropical Gastroenterology & Nutrition Group, Department of Medicine, University of Zambia School of Medicine, University Teaching Hospital, Lusaka, Zambia.
Rose
R
Banda
Vera
V
Yambayamba
Bwalya Daka
BD
Lalusha
Edford
E
Sinkala
Melissa Chola
MC
Kapulu
Paul
P
Kelly
D000284:Administration, Oral; D000328:Adult; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D016099:Endoscopy, Gastrointestinal; D054307:Enterotoxigenic Escherichia coli / Q000472:pathogenicity; D022361:Escherichia coli Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000009:adverse effects*; D012401:Rotavirus / Q000472:pathogenicity; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D012485:Salmonella typhi / Q000472:pathogenicity; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects; D015024:Zambia
D016207:Cytokines; D022361:Escherichia coli Vaccines; D011135:Polysaccharides, Bacterial; C492457:RIX4414 vaccine; D022243:Rotavirus Vaccines; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated