Largest ever African HIV vaccine trial opens in South Africa

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The South African AIDS Vaccine Initiative (SAAVI) and the HIV Vaccine Trials Network (HVTN) this week launched the African arm of a Phase IIb study utilising Merck’s adenovirus trivalent (Ad5 gag/pol/nef) vaccine. The investigators hope to enroll 3,000 HIV-negative men and women over a year, and expect the study to last four years.

The first Phase IIb study (HVTN 502) began enrolling in North and South America, the Caribbean and Australia in 2005, and was known as the STEP study. HVTN 502 was designed to study the vaccine, based on clade B HIV, primarily in men who have sex with men, and some women.

The South African arm, HVTN 503 – also called the Phambili (literally, “moving forward”) study – will examine whether the vaccine has the potential to protect against the clade C virus, the subtype prevalent in South Africa. Analysis of a phase I study presented last year at the Vaccines 06 meeting showed that between 30%-70% of participants who produced responses to subtype B also had responses to subtype A and C.

Glossary

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

clades

The term for the different sub-types of HIV.

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

phase I

The first stage of human testing of a new drug or intervention, typically involving a small number (10-100) of participants who do not have the condition the drug is intended to treat. Phase I clinical trials evaluate safety, side-effects, dosage and how a drug is metabolised and excreted in the body.

vector

A harmless virus or bacteria used as a vaccine carrier to deliver pieces of a disease-causing organism (such as HIV) into the body’s cells to stimulate a protective immune response.

The South African study is also likely to provide data on the vaccine’s effects on heterosexual HIV transmission; more specific information regarding the vaccine’s effects on women; and whether the vaccine works in a population where there is widespread pre-existing immunity to the adenovirus – the viral vector used in the vaccine. Although there are concerns about the effect of natural immunity to adenovirus reducing its effectiveness, Merck are hoping to work around this by utilising unusual types of the adenovirus in the vaccine.

"This trial will answer several major scientific issues that face all of us in the field of HIV-vaccine development," notes Dr Lawrence Corey, HVTN’s principal investigator.

The trial, which will be conducted in Cape Town, Soweto, Klerksdorp, Medunsa and Durban, has attracted support from Archbishop Desmond Tutu, entertainer, Loyiso Bala, and pop group, Freshlyground, all of whom issued their own press releases welcoming the study.

According to an NIAID Q&A webpage, the study organisers have consulted extensively with the community. All participants will receive regular risk-reduction counselling; male and female condoms; and treatment for any sexually transmitted infections (STIs) acquired during the study. In addition, access to circumcision will also be provided to male participants who desire it.