Human Immunodeficiency Virus (HIV)
Since the start of the epidemic in 1980s, more than 70 million people have been infected with HIV and AIDS-related death toll of about 35 million. Sub-Saharan Africa is the region most impacted by the virus, with one out of every 25 adults living with HIV (WHO). In Malaysia, the cumulative number of reported HIV cases is 118,883; the cumulative number of reported AIDS 25,925; while the total number of deaths related to HIV/AIDS is 43,843. At the end of year 2018, it is estimated that 87,041 people living with HIV (PLHIV) in Malaysia, 75,040 of whom were notified through the national surveillance system. About 55% of the reported PLHIV were receiving antiretroviral treatment. More than 70% of HIV new infections are reported among people aged 20 to 39 years, while children aged less than 13 years old are approximately less than 1%.
Since 1987, more than 30 HIV candidate vaccines have been tested in approximately 60 Phase I/II trials, involving more than 10,000 healthy volunteers. Most of these trials have been conducted in the United States and Europe, but several have also been conducted in developing countries (Brazil, China, Cuba, Haiti, Kenya, Peru, Thailand, Trinidad, and Uganda). The results have confirmed the safety of the vaccines, and have provided important scientific information to develop newer generations of candidate vaccines with better ability to induce anti-HIV specific immune responses.
Currently no vaccine is registered. A preventive HIV vaccine is given to people who do not have HIV. There have been no passive preventive HIV vaccines to reach Phase III yet, but some active preventive HIV vaccine candidates have entered Phase III.
RV144 vaccine candidate is a prime-boost combination of two vaccine components (AIDSVAX B/E and ALVAC), given in sequence: one using recombinant canary pox as a vector or carrier to deliver HIV genes and a second containing gp120 protein found on the HIV surface. The RV144 trial in Thailand showed partial efficacy in preventing HIV.
In 2016, the phase IIb-III trial HVTN 702 / “Uhambo” was launched in South Africa, aiming to build on the RV144 results. HVTN 702 tests a new version of RV144 vaccines, adapted for the subtype of HIV common to the sub-Saharan Africa region, where most new HIV infections occur. The trial vaccines are the ALVAC vector vaccine and a two-component gp120 protein subunit vaccine with MF59 adjuvant. HVTN 702 study led by South African researchers, tests efficacy in preventing HIV infection in adults. Results of this vaccine efficacy trial are expected in late 2020.
A therapeutic HIV vaccine is given to a person who already has HIV, designed to improve the body’s immune response to HIV. The use of therapeutic HIV vaccines is being explored, with goals including:
- to slow down the progression of HIV infection
- to eliminate the need for antiretroviral therapy (ART) while still keeping undetectable levels of HIV
- as part of a larger strategy to eliminate all HIV from the body
Current therapeutic HIV vaccine approaches:
- Inactivated whole virus depleted of gp120
- Single or multiple HIV antigens administered as DNA
- Autologous Dendritic Cells
- Viral vectors e.g. poxviruses (canarypox ALVAC-HIV, vCP1452, vCP1433, fowlpox, MVA), adenoviruses (Ad5)
Evidence for Effectiveness
The landmark RV144 Phase 3 clinical trial in Thailand involved 16,395 participants, which evaluated safety and efficacy. Results from this were reported in 2009. The vaccine showed modest efficacy in reducing HIV infection among vaccinees.
In this trial, 8197 of participants were given treatment consisting of two experimental vaccines targeting HIV types B and E that are prevalent in Thailand, while 8198 were given a placebo. The participants were tested for HIV every six months for three years. After three years, the vaccine group saw HIV infection rates reduced by about 30% compared with those in the placebo group.
- Tat therapeutic vaccine, developed by The Italian National AIDS Center,targets HIV-1 transactivator of transcription (Tat) protein. Phase 2 trial of Tat showed statistically significant reduction of blood HIV-1 DNA load that persisted for up to three years post-vaccination.
- Broadly neutralising antibodies, or bNAbs, can prevent many HIV strains from infecting human cells in the laboratory. Researchers have isolated bNAbs from the blood of people living with HIV and studying them in an effort to design novel vaccine candidates. VRC01 is a human monoclonal antibody targeting HIV-1 CD4 binding site. Early-phase clinical trials of VRC01 and another human monoclonal antibody, 3BNC117, showed reduced viral load in HIV-1-infected individuals not on HAART. HVTN 703 and HTVN 704 trials investigate the effectivenes of VRC01. The results of both studies are expected in 2022.
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