Achieving protection against HBV in HIV patients: Finding the best strategy

ABSTRACT

HBV and HIV coinfection is common and entails important morbi-mortality. Vaccination and anti-HBs seroconvertion is a desirable goal in HIV infected patients. New strategies are necessary to predict seroconversion and clinical endpoints. More studies, in the subgroup of HIV patients with poor immunovirological status are needed.

Keywords:

• HBV
• hepatitis
• HIV
• immunization
• vaccine

It is well described that hepatitis B virus (HBV) infection is more prevalent in human immunodeficiency virus (HIV) infected patients, mostly due to shared transmission mechanisms.¹ HIV patients are considered at risk of acquiring HBV, particularly those with known risks factors for co-infection, such as male gender, MSM, drug users and longer time since HIV diagnosis.² Once HIV patients have been exposed to HBV infection, the natural history of both infections are negatively imprinted: HBV behaves in a more aggressive manner, with more chronic infection, more reactivation episodes, accelerated progression to cirrhosis, higher incidence of hepatocellular carcinoma and liver-related mortality.^3,4 HBV infection causes HAART associated disturbances in HIV patients, with early initiation, changes in scheme prescribed with use of more expensive HAART drugs, and more frequent adverse events.⁵

Therefore, determination of HBV serological status and vaccination for those HBV negative are recommended almost invariably in present clinical practice guidelines for HIV positive individuals.^6-8

However, achieving protection against HBV in HIV patients could present as a troublesome issue.

Response to a HBV vaccination schedule in HIV-positive patients depends largely on their immunovirological status. The classic and most described factors affecting seroconversion to HBV vaccine are CD4 counts and HIV viral load at the beginning of vaccination schedule.⁹ An extensive number of studies has been communicated about this issue. Our group recently reported CD4:CD8 ratio as the main variable defining seroconversion to HBV vaccination in HIV patients.¹⁰ However, response rates to vaccination differs widely between studies, considering an important heterogeneity regarding characteristics and immunovirological status of patients included, vaccine administration route and dosing of vaccination (standard 3 dose scheme versus reinforced schemes).

Launay et al. demonstrated in a randomized controlled trial that increasing dose and number of HBV vaccine injections leads to higher proportion of seroconversion to anti-HBs levels considered protective in HIV patients with good immunovirological status (CD4 counts >200 cell/mm³ and undetectable HIV viral load).¹¹ In this scenario, the use of reinforced schemes is currently recommended.

Nonetheless, a recent controlled trial reported that reinforced schemes was not superior to standard scheme in terms of achieving seroconversion in this setting of patients, but leads to to higher levels of anti-HBs.¹²

Higher levels of anti-HBs is a desirable goal, given that the magnitude of the antibody response to vaccination is related to lasting protective levels, which tends to wane over time. A stronger serological response maintains seroprotective levels above the minimal cut-off recommended for a longer period, as recently reported for a follow report by Launay et al.¹³ However, data from whether higher anti-HBs titres obtained with reinforced schemes of vaccination impacts clinical endpoints in the long term are lacking.

Waning anti-HBs over time has been described in immunocompetents individuals in long-term follow up. The vast majority of those who lose anti-HBs seroprotective levels responds to a booster vaccine dose, and are considered protected against HBV.¹⁴ If these consideration is extendable to HIV patients with a persistent good immunovirological status is not known. Reports have shown a positive response to booster vaccination in HIV well controlled patients.^15,16

Data are scarce about the best strategy to achieve seroconversion to HBV vaccination in HIV patients unresponsive to a first scheme of HBV vaccine. A recent randomized controlled trial showed no difference in seroconversion rate with the use of a reinforced scheme compared to standard scheme of vaccination, moreover a higher anti-HBs titres were described in the reinforced scheme group.¹⁷

Another open question is the best alternative to protect against HBV in HIV patients with poor immunovirological status, defined as low CD4 counts with detectable HIV viral load. Most studies excluded these patients, and the ones which considered them, showed that the overall response is low even when reinforced schemes of HBV vaccination were used. HBV vaccination in HIV patients with poor immunovirological status is controversial, recommendations encourage to vaccinate regardless CD4 count,⁶ initially defer HBV vaccination until CD4 count are higher⁸ or defer in unresponsive patients to a first vaccination scheme.⁷

In conclusion, HBV and HIV coinfection is common and involves important morbi-mortality. The anti-HBs seroconvertion is a desirable goal in HIV infected patients. New strategies are necessary to predict seroconversion, as the use of the CD4:CD8 ratio. More studies, in the subgroup of HIV patients with poor immunovirological status are needed.

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

Fondo Nacional de Investigación y Desarrollo en Salud, Gobierno de Chile. FONIS SA14ID0129.