Crucial Clues to HIV Behavior in the Congo Basin: How We Crack Its Complex Code

Significant progress has been made towards achieving the UN 90-90-90 targets to end HIV/AIDS as a public health threat. These goals are that 90% of people with HIV know their status, 90% receive treatment and have their viral load suppressed.

But the epidemic is still far from over. One of the main reasons is the diversity of the HIV group M virus (HIV-1M), which affects the development of vaccines and treatments.

Currently, there are four groups of HIV-1 (groups M, N, O and P). Each of them originated from an independent transmission from a non-human primate to a human. HIV-1 group M (HIV-1M) is responsible for the global AIDS pandemic today. It can encompass subtypes and many recombinant forms called “clades” or “strains”.

To design long-term and globally relevant biological interventions, it is especially important to understand the biological basis of the various types of HIV-1M: their manifestation, their spread and their influence on the magnitude and duration of each HIV-1 sub-epidemics.

I have spent years studying the different stages that HIV-1M has gone through, from its introduction into humans to becoming one of the major viruses circulating in the world. Much of my work has focused on the Congo Basin, a region in the center of the continent, which spans six countries and consists mostly of equatorial forests.

This is where HIV-1M is most diverse, although HIV prevalence in this region is low. Infections have observed nearly all major lineages of HIV-1M described, in addition to unusual and rare strains of the non-M group.

The region is also the site of species-to-species transmission of all HIV-1 groups and the starting point of the circa 1960 global HIV epidemic.

Currently, we do not know why there are 10 times more different strains of HIV-1M in the Congo Basin region than in the rest of the world. This is an important line of research, and it is the one that has concerned me the most in my work.

The main focus of my research has been to assess what makes one strain survive and spread and another does not. Why have so many unusual strains found in the Congo Basin never left the region? Is it possible that the prevalent strains driving HIV epidemics around the world simply infected a person who, after moving to another part of the world, turned out to be an effective transmitter? These are very important questions that field studies struggle to answer.

Nowadays, it is possible to use the function of the different proteins of HIV-1M to assess the biological differences between the various lineages. What my colleagues and I have discovered so far indicates that there are specific biological differences between HIV-1M clades that may explain their uneven spread around the world.

This is important because a successful vaccine or curative strategy must take into account issues relating to the emergence of HIV and anticipate the factors governing this emergence. To be effective, vaccine formulas must cover all emerging strains.

But there are still many unknowns.

A research in progress

In our current study, we used the function of one of the HIV-1M proteins, the Nef protein, to understand the HIV epidemic in Cameroon.

The optimal activity of this protein is to promote the efficient replication of the virus and to make it more transmissible. We used samples from two distinct cohorts: individuals living in remote villages, particularly around the presumed site of interspecies transmission, and others residing in the cosmopolitan city of Yaoundé.

Our preliminary data indicated that up to 18 distinct clades of HIV-1M were circulating in Cameroon.

Despite this great diversity, one clade accounts for approximately 50% of all circulating viruses in both cohorts. Moreover, in the HIV-1M Nef of the different clades discovered in Cameroon, distinct functional activities have been identified, which seems to indicate that these clades have various means of increasing the transmission of HIV-1. In addition, the function of Nef to promote HIV-1M transmission was greater in the Cosmopolitan City cohort than in the other. We can deduce that HIV-1M could be more transmissible in the city than in remote areas.

These data provide further explanation as to why certain clades of HIV have caused global pandemics and not others. Based on these data, for example, specific biological properties of the ancestral clades of HIV-1M may have influenced their epidemiological spread. Thus, these clades were therefore genetically predisposed to successfully spread the HIV epidemic in Cameroon and possibly other parts of the world.

Moreover, these data show that the HIV-1M viruses of the two cohorts follow different evolutionary trajectories, perhaps depending on the networks of sexual partners. These networks are probably much larger in the cosmopolitan city of Yaoundé, where the epidemic continues to progress, than in remote villages. It is possible that the viruses circulating in the densely populated cities of Cameroon were selected to increase transmissibility.

Perspectives

It is impossible to develop a vaccine and a treatment without understanding the precise genetic underpinnings of the predispositions and evolution of the virus. Our research contributes, thanks to the contribution of these major parts, to complete this complex puzzle. Each new discovery brings us one step closer to developing preventive strategies as well as our ability to predict the future emergence and spread of HIV-1M.

Marcel Tongo Passo does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

By Marcel Tongo Passo, Principal Investigator based at Centre for Research on Emerging and Re-Emerging Diseases (CREMER), Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE)