HIV/HBV co-infection provides opportunities

A new report from independent market analyst Datamonitor reveals that the rate of Hepatitis B (HBV) co-infection in HIV infected individuals is increasing among the seven major markets (Japan, US, France, Italy, UK, Germany, Spain), with an average incidence of 7%.

The advent of Highly Active Antiretroviral Therapy (HAART) has led to increased longevity in those infected with HIV and shared epidemiological risk increases the likelihood of these individuals contracting HBV. Although HBV has little impact on HIV disease progression, HIV renders HBV more aggressive and frequent, with co-infected individuals eight times more likely to die of liver damage-related mortality. Datamonitor reveals that inadequate diagnosis of concurrent disease states, lack of effective HBV treatment and HAART hepatoxicity all have a great impact on the effective management of this niche population. It recommends that development of HBV antivirals, preferably with dual HIV and HBV efficacy, would address the obvious gap in treating this co-morbid population, providing an additional opportunity for companies to capitalize on the HIV mono-infected market.

Long-term usage of HAART for the management of HIV has decreased mortality among the HIV-infected population, although this has consequently led to an increasing prevalence of chronic co-infections such as Hepatitis B (HBV) and Hepatitis C (HCV). HBV is 50 to 100 times more infectious than HIV (WHO Hepatitis B guidelines, 2003) and indeed, the likelihood of HIV-infected individuals contracting HBV is 3-6 times greater than non-infected individuals (Bodsworth, 1991). Disease progression of HIV is usually unaltered by co-infection with HBV; although HBV is more frequent and aggressive among the HIV-infected population, resulting in increased incidence of liver damage-related mortality. With increasing access to HAART therapy in both the developed and developing world, Datamonitor believes there is likely to be a concurrent increase in the incidence of HIV/HBV co-infection in the short-to-medium term, although this rate is unlikely to exceed the growth rate observed in HIV mono-infection.

One of Datamonitor's key findings was the lack of awareness and recognition of this co-infected state by both physicians and patients. Early diagnosis of the co-morbid population is affected by physicians' ignorance mainly due to the scarcity of comprehensive treatment guidelines. Datamonitor also found that, within different markets, co-morbid patients were presenting and receiving treatment through a variety of routes within their respective healthcare systems; an additional issue with negative implications for patients' effective management. Datamonitor warns that concurrent early diagnosis of both HIV and HBV disease states is essential to increasing the life span of this co-morbid population. Confirming the presence of both viruses ensures optimum treatment from the onset, thus improving patient prognosis at later stages.

HBV co-infection acts as an additional economic burden to an already expensive HIV HAART regimen (approximately $10,000 per patient in the US). It is therefore more cost-effective to vaccinate the HIV/HBV co-infected population, rather than manage HBV infection with expensive antiviral and immunomodulator therapies. Although HBV vaccines have reduced efficacy in HIVinfected patients, they could still diminish co-infection prevalence.

Based on key opinion leader findings, Datamonitor suggests several actionable points, the first being that the majority of those co-infected with HIV/HBV, i.e. HIV-infected high-risk groups such as intravenous drug users (IVDUs)), be further targeted for diagnosis, vaccination and treatment to minimise infection. This could also be extended to new immigrants in Western regions. Although immigration of HBV infected individuals from endemic countries was thought to have little impact on the general population, it is likely to affect those same high-risk groups. Western markets, such as the UK, with a high degree of immigration from sub-Saharan Africa should therefore reconsider their HBV vaccination guidelines. They should also be aware of the 'relapse' in the male homosexual population with regard to the transmission of parenteral viruses, although this is thought to be relatively rare for HBV.

The main aim of HBV mono and co-infection treatment is the suppression of viral replication, improving liver histology, and the prevention of hepatocellular carcinoma. Ultimately the goal is to achieve complete clearance or eradication of the HBV virus and induce an antibody specific immune response. Datamonitor revealed that currently marketed HBV antivirals only achieve seroconversion in approximately 10% of the HBV mono-infected population and this figure will be significantly lower for the co-morbid populace. In response to this need, a number of companies including Gilead and Idenix/Novartis have recognised an emerging market for increased HBV potency but more importantly, agents capable of seamless integration with HAART regimes. This dynamic is driven further by the current unsuitability of immunomodulators and the increased product saturation of the HIV mono-infected market.

The dual targeting ability of many existing HIV therapeutics such as Gilead's Viread and Emtriva provide opportunities for product lifecycle management with potential tailoring for the treatment of both HBV mono and co-infection. This strategy has been employed successfully for GSK's Epivir and may be extended to MIV-310, a dual-spectrum antiviral announced as part of a recent agreement with Medivir and Boehringer Ingleheim. Idenix/Novartis are taking a different approach, focusing on the mass-HBV mono-infected population with potent developmental agents such as Telbuvidine. Aside from mono-infection, manufacturers should be increasingly aware of the co-morbid population¹s specific needs and that well-defined clinical studies on these groups could provide them with a competitive advantage outside mono-infected populations.

In conjunction with potential commercial support and advocacy of HBV vaccination, Datamonitor believes that with the advent of newer more potent HBV therapeutic agents, targeting countries where HBV is endemic could be profitable with the preparation of a vaccine-like high volume/low cost model. A large-scale production of an efficacious antiviral with eradication rates of 25-50% provided at low cost via collaborations with organizations such as the World Health Organisation (WHO) could achieve this goal.

John Savopolous, Lead Datamonitor Healthcare analyst comments:

'Changing HIV and HBV epidemiology through migration, a current lack of potent HBV therapeutics and early resistance development provides opportunity for those manufacturers possessing dual HBV/HIV antivirals.

'A novel potent HBV antiviral distributed at low cost and high volume may solve the problem of Hepatitis B in the developing faster than current vaccination programs. Such a model could be profitable for firms such as Novartis/Idenix and Gilead raising their profile considerably'