HIV is said to have killed more than 30 million people across the globe since it was discovered in 1983 by Dr Francoise Barre-Sinoussi, at the Pasteur Institute in Paris. Traditionally vaccines have been extraordinary tools to prevent infectious diseases, stop epidemics and save millions of lives. However with regard to HIV, this time honoured concept of a stand-alone prevention modality vaccine seems unlikely. In the global efforts to end the AIDS pandemic an HIV vaccine would be a critical component of a comprehensive combination prevention strategy.
In HIV, ignorance amounts to fear and silence can lead to death. Not seeing, not hearing and speaking about HIV will only exacerbate the epidemic. The Governor of Massachusetts Deval Patrick while speaking at the opening plenary session at the AIDS Vaccine 2012 Conference appealed to the scientists, governments and communities to “come together and stick together to get the job done, for in collaboration lies the solution to problems facing humankind.”
“We have to hope for the best and work for it”, he said.
Due to human and viral diversity there can be no stand alone prevention tool, no golden bullet to control and prevent HIV. Only a combination of preventions can hope to tame the epidemic—treatment as prevention, voluntary medical male circumcision, testing/prevention of pediatric infection, harm reduction, pre exposure prophylaxis, condoms, testing and counselling, drug/alcohol treatment, STI treatment, anti retroviral therapy (ART). The HIV vaccine can be a part of and not a replacement for these proven combination prevention strategies.
While delivering the plenary lecture at AIDS Vaccine 2012, Dr Anthony Fauci of the US National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Health (NIH), reiterated that, “The role of an HIV vaccine in pandemic HIV infection is paramount to maintenance of elimination of the disease as well as its eradication. If we have a dream of eradicating HIV then a vaccine is essential. The HIV prevention strategy has to be a unique paradigm of non vaccine combination prevention modalities plus an HIV vaccine. The degree of impact of an HIV vaccine on ending the AIDS epidemic will depend upon the success of the ongoing non vaccine combination prevention programmes and also on the timing of the introduction of an HIV vaccine and its effectiveness.”
There is no effective AIDS Vaccine available today. Yet a safe and effective vaccine is critical to the control of HIV globally. There are many obstacles in the path of an effective AIDS vaccine. HIV is a difficult retro virus—it makes a reverse copy of itself. No person has spontaneously cleared HIV after being infected with the virus. HIV integrates and establishes infection within first few days, so there is a very narrow opportunity for the immune system to clear the initial infection. The destruction of CD4 T Cells begins immediately. Also there are different modes of transmission; HIV kills the very immune cells which are used in defending the body against HIV; the virus replicates and mutates and the enormous genetic diversity that occurs during replication makes it unrecognizable to the immune system; mutation leads to various sub types of the virus throughout the world—there are 5 main genotypes or clades.
There are over 30 clinical trials of vaccines currently underway in 25 countries in different phases of development. In 2009, results of RV144, the Thai prime boost AIDS Vaccine (ALVAC+AIDSVAX)- a pox virus vector plus a protein– safety and efficacy study which enrolled over 16,000 Thai men and women showed that the regimen reduced risk of HIV infection by 31%. The greatest protection (60%) was seen in the 1st year after the six injections regimen of the vaccine had been given. This was the first data showing that an AIDS Vaccine can block HIV infection in humans and gave proof of concept for a protective vaccine. Within 9 months of the result, an international initiative was underway to select the assays used to analyze RV144 samples for correlates of risk. Follow on research began screening in Thailand in 2012. Trial participants who remained negative will be offered to enroll in smaller phase2 studies to look at the safety and effect of late boost regimens, meaning that participants will get additional vaccinations (3 different single vaccine or combination regimens) and safety and immune responses will be evaluated. Additional efficacy trials by a consortium called the P-5 or Pox protein Public Private Partnership are being launched in Thailand and South Africa to confirm and improve on the efficacy seen in RV144. The goal is to improve upon durability and magnitude of early efficacy of 60% by adding a boost to ALVAC+gp 120 at 12 months as well as a different adjuvant MF59 to prolong the level of protection observed at 12 months. Three follow up trials are planned—a South African efficacy trial of P5 regimen to see if results can be repeated/improved in a high incidence setting; a South African discovery trial with an adaptive design to gather information on multiple vaccine candidates; and an efficacy trial using the P5, RV144 like regimen among men who have sex with men (MSM) in Thailand.
There is another large scale vaccine efficacy trial going on—HVTN 505. This phase IIb trial of a DNA prime/ Ad5 boost vaccine regimen is being tested in 2000 gay men, MSM and transgender women in the USA. Launched in 2009 the trial changed its protocol in 2011 adding HIV acquisition as a co primary endpoint. The trial is also looking at if the vaccine can reduce viral load in participants who were HIV negative when they got the vaccine, and later acquired HIV through sex or other risk related behavior. As of now it is the only ongoing AIDS vaccine efficacy trial in the world. (RV144 is in follow up stage). Data from this is expected in 2013, and that from phase 2 boost study of RV144 in 2014.
There are several clades of HIV-1. So there will be need of regional vaccines—what works in one region will not work in another. The Thai vaccine is a combination of Clades A and E. The clade C is the most common (50% worldwide) and also most prevalent in India as well as Africa. The trials which P5 are accelerating in South Africa are using the same vaccine with clade C. but it is too early to say if it will work or not.
If all goes well, the first vaccine is not expected before 2022. Before it can have any public health effect it will have to be manufactured and then licensed. This often delays the process as happened in RV 144 where phase 3 trial delayed by a one year. After licensing, phase 4 trials would be conducted and only then will it be ready to be delivered to the target population.
Mitchell Warren, Executive Director of AVAC-Global Advocacy for HIV Prevention, in an exclusive interview to Citizen News Service (CNS), stressed that a vaccine is going to be critical in turning the tide against HIV/AIDS and that the cost of not developing a vaccine is far more than the cost of developing one. He said that, “We need to build upon RV144, accelerate the studies of P5, get the answers faster and try to do better than 31%. We may find that the vaccine works better as it has been tweaked. But if follow up trials do not show that it works, it will be hugely disappointing. That is why we need to accelerate researching other areas as well. So we need to make some very tough decisions about what we will and will not do. We need researches to do urgent things. If we do not develop a vaccine we will not be able to see an AIDS free generation.”
Even a partially effective preventive AIDS vaccine could have a tremendous impact on the number of new HIV infections. Modeling the potential impact of an AIDS vaccine provides a basis for calculating the potential cost savings that a vaccine could generate by reducing the number of additional people requiring ART. Each infection prevented by an AIDS vaccine would reduce the number of people who would eventually require a lifelong regimen of antiretroviral treatment. Under current trends, an AIDS vaccine could avert between 5.2 and 10.7 million new infections and save between US $46 billion to $95 billion in averted costs of ART provision alone between 2020 and 2030.
Myron Cohen, Director, Institute for Global Health, university of North Carolina, is concerned that, “We have 34 million people living with HIV who we have to treat NOW for their health and to prevent transmission. The mass treatment of HIV is only a bridge to a simpler, modified intervention, to a cure, to a vaccine. Now is the time to redouble the efforts to achieve our aspirational goals.”
We need to have persistence, and patience and partnerships. For as Francis Bacon said, they are ill discoverers that think there is no land, when they can see nothing but sea. (CNS)