For patients with HIV viral load is key in immune response to yellow fever vaccine

Michael Carter
Published: 02 February 2012

Viral load is the only factor associated with a poorer antibody response to the yellow fever vaccine in patients with HIV, according to a French study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

For patients vaccinated after diagnosis with HIV, an undetectable viral load was the “unique determinant” of the preservation of protective levels of antibodies.

“This study of a large series provides new data about the immunogenicity of yellow fever immunisation in HIV patients,” comment the authors.

The re-emergence of yellow fever in endemic countries in sub-Saharan Africa and South America is causing great concern. The fatality rate is as high as 50% for symptomatic patients.

However, a live attenuated vaccine that provides high levels of protection against this infection is available. Some 99% of patients have antibodies against the infection within 30 days of immunisation, and protection may persist for 30 years (however, the World Health Organization [WHO] recommends a booster dose of the vaccine after ten years).

Yellow fever vaccine and booster doses are recommended for HIV-positive patients with a CD4 cell count above 200 cells/mm3 who live in – or, in some cases, are visiting – endemic countries. As a live vaccine, there are some concerns about the safety of immunisation for patients with lower CD4 cell counts.

However, there is limited information on the efficacy and safety of the vaccine in patients with HIV.

Therefore, investigators in Paris designed a study with a primary objective of assessing the proportion of HIV-positive patients vaccinated against yellow fever (primary and booster doses) who did not develop a sufficient antibody response to protect them against this infection.

The study was conducted between 2007 and 2008 and involved 364 patients.

An insufficient response to the immunisation was defined as an antibody titre below 1:10. 

Overall, 93% of patients had an antibody titre above 1:10. This included 92% of patients who had received the vaccine ten years before the sampling in this study.

“Yellow fever immunisation is effective in HIV patients,” comment the authors. “The proportion of patients with an antibody titre >1:10 [98%] was especially high within one year following immunisation.”

A total of nine of the 240 patients who were vaccinated after their diagnosis with HIV had an antibody titre below the protective level. Viral load in these patients was significantly higher compared to individuals who had protective antibody tires (p < 0.03). Each log10 increase in viral load doubled the risk of having a tire below the crucial 1:10 threshold (OR = 2.1; 95% CI, 1.2-3.78).

Analysis of the 79 patients who received their initial dose of the vaccine after their diagnosis with HIV found an even stronger association between viral load and the lack of a protective antibody titre (OR = 3. 73 per 1010; 95% CI, 1.14-12.28).

“Suppressed plasma viral load at baseline was the unique determinant for the persistent of levels of antibodies above 1:10,” note the authors.

Shorter duration of HIV suppression below 400 copies/ml was also associated with an antibody titre below 1:10 (OR = 1.05 per year; 95% CI, 1.005-1.09).

At the time of immunisation, 14 patients had a CD4 cell count below 200 cells/mm3. Furthermore, six of these individuals also had a viral load above 400 copies/ml. The interval between administration of the vaccine and measurement of antibody response was a median of 4.6 years. All the patients had an antibody tire above 1:10.

The investigators believe their results have implications for the care of HIV-positive patients.

They suggest that “in cases where there is travel to a yellow fever-endemic country, we suggest that neutralizing antibody determination be performed prior to departure, whatever the time since a previous immunisation, especially in patients with non-controlled HIV RNA at the time of travel or immunisation.”

The authors conclude, “patients with non-protective neutralising antibodies might be revaccinated earlier than recommended by current guidelines, whereas revaccination might be avoided in patients with persisting…antibodies.”


Pacanowski J et al. Plasma HIV-RNA is the key determinant of long-term antibody persistence following yellow fever immunization in a cohort of 364 HIV-infected patients. J Acquir Immune Defic Syndr, online edition. doi: 10.1097/QAI.0b013e318249de59, 2012 (click here for the free abstract).

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