CRI report: Since the discovery of HIV as the causative agent of AIDS in the early 1980s, research has made tremendous strides to transform this deadly disease into a manageable one. The introduction of highly active antiretroviral therapy (HAART) in the 1990s promoted the combination of drugs from different classes to block HIV replication and result in undetectable viral loads. This came with a price: increased pill burden. Companies such as Gilead and Bristol-Myers Squibb (NYSE:BMS) addressed this issue by introducing fixed-dose combination drugs (FDCs) and single-tablet regimens (STRs), such as Truvada (emtricitabine / tenofovir disoproxil fumarate) and Atripla (efavirenz / emtricitabine / tenofovir disoproxil fumarate). With efficacy and side-effect profiles continuously improving over time, antiretroviral therapy (NYSE:ART) has allowed patients to initiate therapy earlier. - PharmaFocus: HIV - R&D Strategies towards Cure and Prevention
The World Health Organization (WHO) released new guidelines during the 7th International AIDS Society meeting in July 2013, recommending the initiation of ART when CD4 T-cell counts drop below 500 cells/mm3. Furthermore, countries such as the US and China have already adopted the "test-and-treat" approach, offering treatment to people upon diagnosis, regardless of their CD4 counts. -PharmaFocus: HIV - R&D Strategies towards Cure and Prevention
According to the WHO, the earlier initiation of ART is going to have a positive impact on the HIV market, increasing the number of people eligible for therapy from 17 million to 26 million (WHO, 2013).
Despite Successful ART, Significant Unmet Needs Remain for HIV Cure and Prevention -PharmaFocus: HIV - R&D Strategies towards Cure and Prevention
Despite the success of ART in maintaining low viral loads and curbing transmission rates, treatment is still expensive, limiting access to medication for eligible people. With the recent WHO guidelines, GlobalData expects a boost in the demand for ART. Other issues associated with ART include low compliance, especially to multi-tablet regimens, which can result in treatment failure, and emergence of resistant strains. Therapeutic vaccines can help control viral loads for prolonged periods of time, which represents a functional cure that subverts compliance issues. There are also a number of patients who do not respond to ART, who are in need of novel salvage therapy options.
In addition to treating infected patients, the FDA approval of chemoprophylactic agents, such as Gilead's Truvada, for pre-exposure prophylaxis (PrEP) provided a new approach to prevent HIV infections. However, GlobalData believes that the cost, potential long-term toxicities, and compliance issues are expected to limit its use to people belonging to high-risk groups, such as serodiscordant couples. In order to address the wider population in a cost-effective way, there is a need for a prophylactic vaccine that can protect patients from a broad spectrum of viruses belonging to the most common clades. GlobalData, therefore, believes that demand for an effective HIV vaccine justifies companies undertaking more vaccine efficacy trials to identify a successful candidate.
Biotech, Academia and Governments in Hot Pursuit of New Approaches to Eradicate HIV - PharmaFocus: HIV - R&D Strategies towards Cure and Prevention
HIV's unique biology poses several barriers to its eradication. The development of a prophylactic vaccine poses several challenges, including viral diversity (different amino acid sequences between the nine subtypes), rapid and error-prone viral replication resulting in mutant genomes that can evade the immune system, and a lack of correlates of protection, i.e., immune markers that can be used as indicators of protective immune response. Also, HIV's ability to "hide" in latent reservoirs by integrating into the host genome prevents viral clearance as quiescent viruses escape the inhibitory effects of ART.
Organizations such as the International Vaccine Initiative and the HIV Vaccine Trials Network, funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH), orchestrate the collaborative efforts between academia and biotech companies towards the development of a preventative vaccine against HIV. There is also intense research in the field of therapeutic vaccines, which aims to elicit immune responses that will clear the infected cells and control viral replication, leading to a functional cure without the need for ART. Also, the case of the Berlin patient, the first reported case of a sterilizing cure, has spurred research towards a sterilizing cure using gene therapies and autologous or heterologous stem cell transplantation. Another approach to eradicate HIV that is gaining momentum utilizes cancer drugs known as latency reversal agents, with the best-studied being Merck's Zolinza (vorinostat).
Novel Combinatorial Regimens Can Lead to a Functional Cure - PharmaFocus: HIV - R&D Strategies towards Cure and Prevention
Achieving a functional cure is still a major medical challenge. Efforts targeting different aspects of HIV, such as latency reversal agents to reactivate the reservoir, therapeutic vaccines to generate CD4/CD8 T-cell responses, and nucleases capable of rendering stem cells non-receptive to HIV infection, are beginning to yield preliminary results. However, the success of a functional cure could come from an intervention that combines these approaches. Once latently infected cells are reactivated, administered antiretrovirals will prevent productive infection of additional CD4 T-cells. To prevent re-establishment of the reservoir and kill resistant CD4 T-cells after reactivation, therapeutic vaccination that stimulates CD8 T-cell responses can be used.
New combinatorial therapies present a unique opportunity for small biotech companies and academic laboratories to combine their forces under the support and guidance of regulatory bodies and government institutions. GlobalData expects that the first successful regimen will attract Big Pharma, which can leverage its resources to conduct large-scale trials and successfully market the therapy.