Undetectable viral load at time of immunisation enhances yellow fever vaccine protection for people with HIV

Viral suppression at the time of immunisation is the most important determinant of long-term response to yellow fever vaccination among people with HIV, Swiss investigators report in Clinical Infectious Diseases. Every person with an undetectable viral load at the time of first yellow fever vaccination continued to have a protective response ten years after vaccination, they found.

“Persons infected with HIV demonstrated good short-term immune response to YFV [yellow fever vaccination], which decreased to 75% ten years p.v. [post vaccination],” comment the authors. “The long-term immune response of patients with HIV RNA suppressed at vaccination remained unimpaired for up to ten years.”

The investigators believe their findings have implications for vaccination strategies, writing: “HIV-infected patients mount a long-standing protective immune response to YFV up to at least ten years if they are vaccinated while remaining on successful cART [combination antiretroviral therapy]…until further data are available a single booster after ten years seems to be adequate to restimulate the vaccine response in the event of new travel to a YF [yellow fever] endemic area.”


immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


Because of the possibility that a positive result from a single HIV test is, in fact, a false positive, the result is described as 'reactive' rather than 'positive'. If the result is reactive, this indicates that the test has reacted to something in the blood and needs to be investigated with follow-up tests.


Immunisation is the process whereby a person is made immune or resistant to an infectious disease, typically by the administration of a vaccine. Vaccines stimulate the body’s own immune system to protect the person against subsequent infection or disease.


virological suppression

Halting of the function or replication of a virus. In HIV, optimal viral suppression is measured as the reduction of viral load (HIV RNA) to undetectable levels and is the goal of antiretroviral therapy.

Yellow fever is a mosquito-borne severe viral haemorrhagic disease. There is no antiviral treatment. However, there is a highly effective vaccine. The World Health Organization issued guidance in 2013 recommending that individuals should receive yellow fever vaccination boosters every ten years to obtain life-long protection against the disease.

Many HIV-positive individuals live in or travel to areas where yellow fever is endemic. The long-term response to yellow fever vaccination in people with HIV is poorly understood. Investigators from the Swiss HIV Cohort Study therefore identified 247 people with a documented first yellow fever vaccination after their diagnosis with HIV. Stored blood samples were examined to see if individuals had an immune response at one, five and ten years post-vaccination. A yellow fever plaque reduction neutralisation titre (PRNT) of 1: >10 was regarded as reactive and protective. Predictors of vaccine response were also examined.

The majority of people were from sub-Saharan Africa. Most (82%) were taking cART at baseline and 83% had an undetectable viral load (below 400 copies/ml). Median CD4 cell count was 536 cells/mm3.

Yellow fever vaccination is only recommended for asymptomatic HIV-positive people with a CD4 cell count above 200 cells/mm3. This is because it is a live-attenuated vaccine and therefore poses significant health risk for people with very weak immune systems. Despite this recommendation, the investigators identified eleven individuals who were immunised against yellow fever while their CD4 cell count was dangerously low.

Overall, PRNT was reactive in 46% of people before vaccination. A protective immune response was present one, five and ten years post-vaccination in 95%, 86% and 75% of people, respectively.

In people with suppressed viral load at the time of immunisation, the proportion with reactive PRNT remained consistently high: 99% at year one, 99% at year five and 100% at year ten.

An undetectable viral load at the time of vaccination was the single biggest determinant of long-term response to the vaccine.

The authors recommend that people with HIV should be vaccinated against yellow fever once their viral load is suppressed and that they should receive a booster after ten years if they remain on suppressive cART. However, people who were vaccinated while their viral load was detectable should either have their immune response to the vaccine measured or receive a booster vaccination, irrespective of the time since first yellow fever vaccination.


Veit O et al. Long-term immune response to yellow fever vaccination in HIV-infected individuals depends on HIV-RNA suppression status: implications for vaccination schedule. Clin Infect Dis, online edition, 2017.