Review of preventative HIV vaccine clinical trials in South Africa

Abstract

New HIV infections continue relentlessly in southern Africa, demonstrating the need for a vaccine to prevent HIV subtype C. In South Africa, the country with the highest number of new infections annually, HIV vaccine research has been ongoing since 2003 with collaborative public-private-philanthropic partnerships. So far, 21 clinical trials have been conducted in South Africa, investigating seven viral vectors, three DNA plasmids, four envelope proteins, five adjuvants and three monoclonal antibodies. Active vaccine candidates have spanned subtypes A, B, C, E and multi-subtype mosaic sequences. All were well tolerated. Four concepts were investigated for efficacy: rAd5-gag/pol/nef showed increased HIV acquisition in males, subtype C ALVAC/gp120/MF59 showed no preventative efficacy, and the trials for the VRC01 monoclonal antibody and Ad26.Mos4.HIV/subtype C gp140/ aluminum phosphate are ongoing. Future trials are planned with DNA/viral vector plus protein combinations in concert with pre-exposure prophylaxis, and sequential immunization studies with transmitted/founder HIV envelope to induce broadly neutralizing antibodies. Finally, passive immunization trials are underway to build on the experience with VRC01, including single and combination antibody trials with an antibody derived from a subtype-C-infected South African donor. Future consideration should be given to the evaluation of novel strategies, for example, inactivated-whole-virus vaccines.

Linking market authorizations of medicines with disease burden in South Africa

“…if companies do not innovate/manufacture and/or submit applications for marketing authorisations, medicines will not get approved irrespective of available regulatory resources. Most research and development activities take place outside of South Africa, although South Africa is very actively involved in clinical research [19,20]. The study only evaluated approvals and therefore does not take into consideration applications for registration of medicines which may have been removed by the applicant company or may have been rejected by the MCC.…”

“…South Africa is almost never in the first wave of countries in which companies seek registration for new medicines. However, South Africa is an active participant in international clinical trials on new treatments that are being developed for some of the top diseases that represent a high burden of disease in the country such as HIV/ AIDS and cancer [19,20]. Even so many of the treatments tested on patients during clinical trials conducted in South Africa do not eventually get registered in the country [21].…”

Effectiveness of Health Interventions towards HIV/AIDS in Developing Countries: A Systematic Review

“…Interventions based on demandside described findings including communication, education and information and peerbased interventions on outcome of HIV are unsatisfactory as they rarely reduce prevalence or incidence of HIV. Few studies and trials showed in reviews assessed interventions for increasing circumcision and pre exposure prophylaxis demand, though data from these components are still in emerging stage [110][111][112][113][114][115][116]. Additional research is needed for understating the reason of decreased uptake for these approaches and assessments needed for improved interventions to increase the adherence and uptake.…”

A recombinant measles virus vaccine strongly reduces SHIV viremia and virus reservoir establishment in macaques

“…Tested in phase I/IIa trials, this vaccine candidate has been shown to be safe and immunogenic 7 . Currently, this vaccine approach is undergoing two phase 2b-3 clinical evaluations in South Africa (HVTN 705) and the United States (MOSAICO) 8 . Another live vector that persists in the host, rhesus cytomegalovirus (RhCMV), has been evaluated in non-human primates challenged with SIVmac251 9 .…”