Human Immunodeficiency Virus (HIV) is a lentivirus that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. HIV is transmitted through a body fluids containing HIV, such as blood and semen.
There are two types of HIV known to exist; HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and is the cause of the HIV pandemic. HIV-2 has lower infectivity compared to HIV-1 and is largely confined to West Africa.
HIV infects primarily vital cells in the human immune system such as helper T-cells (CD4+ T cells), macrophages (white blood cells), and dendritic cells (T-cell activators). HIV infection leads to low levels of CD4+ T cells through several mechanisms including:
- direct viral killing of infected cells
- increased rates of apoptosis (programmed cell death) in infected cells
- killing of infected CD4+ T cells by CD8 cytotoxic lymphocytes that recognize infected cells.
- death of uninfected blood cells (‘bystander effect’).
When CD4+ T cell numbers decline below a critical level, immunity is lost, and the body becomes progressively more susceptible to opportunistic infections.
Most untreated people infected with HIV-1 eventually develop AIDS. These individuals mostly die from opportunistic infections or malignancies associated with the progressive failure of the immune system. HIV infection in humans is considered pandemic by the World Health Organization (WHO) and from its discovery in 1981 to 2006 HIV has killed more than 25 million people.
There are two defining characteristics of HIV that makes it difficult to effectively treat:
- Rapid mutations: The replication cycle of HIV can be as short as about 1.5 days from viral entry into a cell, through replication, assembly, and release of additional viruses, to infection of other cells. In addition HIV lacks proofreading enzymes to correct errors made when it converts its RNA into DNA via reverse transcription. The combination of the short replication-cycle and high error rate causes the virus to mutate very rapidly, resulting in a high genetic variability of HIV.
- Attacks the immune system: HIV attacks the very cells that are in place to protect the body from infections and when CD4+ T cell numbers decline below a critical level, immunity is lost. Loss of immunity leaves the body with severely reduced defenses to fend off opportunistic infections and keep HIV in check or to protect against other infections.
Current HIV therapy
The most widely used therapies for HIV are antiretroviral drugs, referred to as Anti-Retroviral Therapies (ART) which is a combination of at least three medications targeting at least two different parts of the virus life cycle. All though the trigger points from when ART is initiated varies from country to country the proportion of diagnosed patients receiving ART is relatively constant across the major markets of the USA and EU at 66% to 78%.
The individual drug works by disrupting one or several of the stages of the virus’ replication cycle:
- ribonucleoside /nucleotide (the building blocks of RNA) analogues and nonnucleoside analogues that inhibit the enzyme responsible for replicating the virus’ genetic material (reverse transcriptase).
- Maturation inhibitors that inhibit the viral protease that processes immature precursor proteins and confers infectivity.
- Entering new cellsintegration of viral genetic material into human chromosomes (integrase inhibitors).
- By using combinations of anti-retrovirals the goal is to create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility drug resistance. The combination therapies is also referred to as Highly Active ART (HAART).
The primary goals of antiretroviral therapy are to improve and/or preserve immune function and reduce HIV-associated morbidity and mortality. Through disruption of the replication and spread of viral particles within the body, ART aims to reduce viral load, leading to minimization of the pathogenic consequences of viral colonization of host cells (primarily, reduced T cell numbers and consequent compromising of the immune system). These therapies do not remove infected cells from the body.
There are several concerns about ART regimens. The drugs can have serious side-effects. Regimens can be complicated, requiring patients to take several pills at various times during the day. If patients miss doses, drug resistance can develop. ART treatment is also costly and resource-intensive.
The HIV therapy market
There were an estimated 33.4 million people living with HIV globally in 2008 with 1.1 million infected HIV patients in the 6 major markets; US, France, UK, Germany, Spain and Italy. The global HIV infected population might be divided by effectiveness of treatment as judged by deaths relative to prevalent population as set out as listed below. This may give a general indication of current availability of antiretroviral therapy (ART) drugs, which is the only HIV therapy available in the market today, and willingness or capacity to pay for expensive therapies.
- Highly effective or highly available treatment (<2 % deaths per year) 2.14 million
- Moderately effective or moderately available treatment (2 to 4 % deaths per year) 4.23 million
- Poorly effective or low availability of treatment (>6 %deaths per year) 26.88 million
Datamonitor estimates the value of antiretroviral sales in the seven major markets (France, Germany, Italy, Japan, Spain, UK and USA) at $11.7bn in 2008 growing to $17.6bn in 2016, representing a Compound Annual Growth Rate (“CAGR”) of 5.6%.
In 2008, 2.7 million people were newly infected with HIV and 2 million died from AIDS. The growing number of patients is being driven by a number of factors including a rise in the number of HIV-infected patients accessing treatment, because of increased life expectancy as a result of improved therapy and higher transmissions of HIV in some countries. Immigration from areas of high prevalence is also expected to contribute to the growing number of HIV-infected individuals in the seven major markets. There are 32 products listed globally by Adis R&D Insight as being launched for the treatment or prevention of HIV infections, although there are many more associated with the treatment of AIDS associated comorbidities and complications.