Hi Sujit,
The following are my answers:
1. The PICOs are:
P (Population of interest): People aged between 18 and 40.
I (Intervention or exposure): HIV vaccines (two combination vaccines to prevent HIV infection) that are part of the PrEPVacc study.
C (Comparison): A placebo vaccine.
Outcome: Reduction in the risk of HIV infection (Prevention of HIV infection).
S (Study design): Clinical trial (Randomised controlled trial), OR
S (Setting): Eastern and Southern Africa (four trial sites in Uganda, Tanzania and South Africa).
2. The comparison arm of an HIV vaccine study can be a placebo vaccine, because: (i) we are uncertain whether a new HIV vaccine is better than a placebo vaccine in order to be considered efficacious/effective; and (ii) there is currently no proven effective HIV vaccine which is already in use to prevent HIV infection. Therefore, we can test a new HIV vaccine against a placebo vaccine.
To date, the only HIV vaccine that had shown any success in protecting against HIV was the RV144 vaccine. It was developed in Thailand, and reduced infection rates by almost a third after three years. However, previous trials in South Africa to test the RV144 was stopped in February 2020 after interim results found it was not working.
3. Sometimes a trial needs to stop early as the study hypothesis is shown to be unprovable based on the statistical analysis of the data obtained early in the study (usually done at a planned interim analysis). In the PrEPVacc trial, two different combinations of HIV vaccines were tested to see if either could prevent infection in populations particularly at risk of infection.
However, the final results and analysis of individual products are awaited, and the final report of the PrEPVacc trial will be available in the second half of 2024.
If the interim analysis fails to prove the study hypothesis, there is no benefit to balance against subjecting the trial participants to potential risks. However, the PrEPVacc’s trial safety group reviews the safety information of participants twice a month, and has no concerns about the safety of the vaccines.
4. The statistical rationale of completing the study in Uganda, Tanzania and South Africa (not in the US or Europe): (i) more than 25 million people are living with HIV (PLWH) in sub-Saharan Africa, and about 39 million people worldwide, i.e. approximately two thirds of the world's population of PLWH reside in sub-Saharan Africa (highest burden); and (ii) Eastern Africa (Uganda, Tanzania) and Southern Africa (South Africa), in particular, continues to record the highest prevalence and incidence rates worldwide.
5. The rationale for using an RCT to evaluate an HIV vaccine, rather than another epidemiologic study design: (i) the randomisation controls for any confounding effects (genetics, socio-demographic factors, co-infection with other pathogens, etc.); and (ii) the blinding reduces information biases. Therefore, RCT (with blinding) is considered to be the best method for measuring HIV vaccine efficacy/effectiveness.
Thanks!
Madhutandra
