Current HIV prevention strategies include a range of behavioural and biomedical interventions, as well as combinations of interventions. Among others, behavioural interventions include those to reduce sexual risk behaviour (Naranbhai 2011, Ojo 2011, Wariki 2012), interventions to improve uptake of HIV testing (Bateganya 2010, Vidanapathirana 2005, Wei 2011), and interventions delivered by telephone (van-Velthoven 2013). In addition to the correct and consistent use of condoms (Weller 2002), some key biomedical HIV prevention interventions include antiretroviral "treatment as prevention" (Anglemyer 2013) and pre-exposure prophylaxis (Okwundu 2012), antiretroviral prophylaxis for preventing mother-to-child HIV transmission (Siegfried 2011), male circumcision (Siegfried 2009, Wiysonge 2011), and the use of topical microbicides (Obiero 2012).
Many believe that a vaccine is the most promising way of ending the HIV epidemic. The first successful eradication of an infectious disease ever achieved in history was done using a vaccine (Fenner 1988). The features of an ideal vaccine include safety, cost, long shelf life, ease of administration and effectiveness.
Description of the intervention
A vaccine is a preparation of a weakened or killed pathogen, or a synthetic substitute of a portion of the pathogen's structure that upon administration stimulates antibody production or cellular immunity against the pathogen but is incapable of causing severe infection.
Vaccines are a cost-effective method of controlling infectious diseases (Stratton 2002). The successful eradication of smallpox using vaccines and the development of an effective vaccine against a HIV-related virus (i.e. feline immunodeficiency virus) (Mazzetti 1999, Yamamoto 2006), raised hope of finding a vaccine against HIV. Thus, substantial research effort is being spent on finding such an effective vaccine. One of the greatest challenges to developing a preventative HIV vaccine is the diversity of HIV-1 isolates. Envelope (Env) gene sequences can differ by as much as 35% between isolates from different clades and by as much as 10% within a clade (McBurney 2007).
The ability of HIV to integrate itself into the DNA of the host also poses a challenge to vaccine development (Johnson 2008). Presently, there are six types of experimental HIV vaccine (HVTN 2009) namely :
Peptide vaccine: made of tiny pieces of proteins from the HIV virus
Recombinant subunit protein vaccine: made of bigger pieces of proteins that are on the surface of the HIV virus. Examples of a recombinant subunit protein are gp120, gp140, or gp160 produced by genetic engineering.
Live vector vaccine: non-HIV viruses engineered to carry genes encoding HIV proteins. The genes are inserted into another vector, which carries them into the body's cells. The genes in turn produce proteins that are normally found on the surface of the HIV virus. This type of vaccine most resembles the HIV virus but is not harmful. Many vaccines used today, like the smallpox vaccine, use this approach.
DNA vaccine: uses copies of a small number of HIV genes which are inserted into pieces of DNA called plasmids. The HIV genes will produce proteins very similar to the ones from real HIV.
Vaccine combination: uses any two vaccines, one after another, to create a stronger immune response. Often referred to as "prime-boost strategy."
Virus-like particle vaccine (pseudovirion vaccine): a non-infectious HIV look-alike that has one or more, but not all, HIV proteins.
How the intervention might work
A preventive HIV vaccine would protect HIV-uninfected people from getting infected. When the human body encounters a microorganism, the person's immune system attacks the invading microorganism. If it successfully overcomes the microorganism, the immune system continues to "remember" and to mount a defence against the microorganism the next time it enters the body. An HIV vaccine is designed to assist the immune system to recognize and attack the virus whenever it is encountered.
Research on HIV vaccines and prevention relies strongly on preclinical studies in macaque models for the identification and evaluation of potential vaccines or prophylactic treatment strategies (UNAIDS 2004). Animal trials are used to screen for preventive interventions that induce sterilising immunity. Unfortunately, most of the vaccine candidates so far tried have failed to induce sterilising immunity (Amara 2001, Barouch 2000, Rose 2001, Shiver 2002).
The complete inadequacy of the natural immune response against HIV is another challenge as is its inability to eradicate the virus once primary infection has been established. There is no documented case of spontaneous recovery from HIV infection. However, there are HIV-infected individuals who do not progress to AIDS as well as HIV-negative individuals who have been exposed to the virus multiple times suggesting that natural immune responses to HIV may be protective in rare individuals. Understanding the correlates of protective immunity to HIV infection is critical to efforts to develop preventive HIV vaccines as well as to determine the feasibility of treating HIV infection by boosting immunity to HIV (Haynes 1996).
There are reports of commercial sex workers who have remained uninfected despite frequent exposure to HIV. In such persons, HIV-specific mucosal antibody responses may exist and play a role in resistance against HIV (Dorrel 2000).
Demographic factors and genetic background of the human populations in HIV vaccine trials remain a source of potential variation in responses observed in such trials, yet empirical data remain limited on the impact of those factors. Coinfections, particularly those that may modulate the immune response, are a further concern for HIV vaccine trialists (de Bruyn 2010).
Why it is important to do this review
A number of clinical trials have evaluated the effectiveness of HIV vaccine candidates. These include the recently concluded (the world's largest) HIV vaccine trial, RV144 Phase III HIV Vaccine, among volunteers in Thailand, which tested a combination of two vaccines namely, ALVAC-HIV vaccine tagged "the prime" and AIDSVAX vaccine tagged "the boost" (Berkhout 2009). However, there has not been any published systematic review of vaccine trials. This review will collate the evidence to inform health care providers on the use of vaccines for the prevention of HIV infection.