Viral Diversity in Africa

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The diversity of HIV-1 and the other AIDS virus, HIV-2, were discussed by Professor Souleymane Mboup of Senegal in a plenary session at the 12th ICASA in Burkina Faso on Wednesday 12 December.

Prof Mboup presented a picture of rapid change and increasing complexity, especially in West Africa. No two countries have the same distribution of HIV-1 subtypes and there are even marked differences within countries, particularly Nigeria and the Democratic Republic of the Congo.

Having been one of the pioneers of research on HIV-2, Prof Mboup discussed the differences between the two AIDS viruses. HIV-1 causes faster loss of CD4 cells than HIV-2 and thus faster progression. HIV-1 is much more easily transmitted from mothers to babies and also, it seems, through sex. Differences between viral proteins make NNRTIs ineffective against HIV-2: early suggestions that HIV-2 might protect against HIV-1 are now known to be false, and in fact co-infected people progress faster than those with single infections (see below). The two viruses are related to different SIVs (of chimpanzees and sooty mangabey monkeys respectively).

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.

recombinant

An organism, cell or genetic material formed by genetic recombination (or reconstruction).

gag

One of the three proteins encoded within the retroviral genome.

translation

The step in the HIV life cycle that follows transcription in which the genetic information contained in HIV mRNA is used to build HIV proteins with the host cell’s protein-making machinery. Once these HIV proteins are produced, they can combine with copies of HIV’s RNA genetic material to form new, complete copies of HIV.

sexually transmitted diseases (STDs)

Although HIV can be sexually transmitted, the term is most often used to refer to chlamydia, gonorrhoea, syphilis, herpes, scabies, trichomonas vaginalis, etc.

Reviewing HIV-1 subtypes, circulating recombinant forms of the virus appear increasingly important in a number of countries and regions of the world, but nowhere more so than in West Africa. The dominant virus in his own country is now HIV-1 CRF02-AG, a combination of subtypes A and G. This was responsible for most of the recent increase in a number of countries and was particularly common in HIV-2 co-infection. Recombinants between Group M viruses (A to K) and Group O viruses were now being seen.

The group O viruses are sufficiently different from "standard" viruses that standard antibody tests are at best insensitive in newly infected people. Also, commercial viral load tests don't work on them (though new tests are being developed both for group O and for HIV-2).

Prof Mboup asked how we could be sure that scientific findings from work on subtype B viruses really applied across other subtypes, especially on pathogenesis.

A more immediate issue that arises concerns treatment, where a number of "resistance mutations" seen in subtype B appear as common natural variants in viruses of other subtypes.

For the future, the obvious concern is for vaccine development. Cross-protection may however be possible, especially with vaccines aimed at creating cellular immune responses.

Implications for Vaccine Research

On Thursday morning, Professor Mboup's message was reinforced by the US researcher Professor Max Essex from Harvard University, who gave a plenary talk on vaccine research. He was able to report some progress in the field, towards a greater number of vaccine research projects based on African HIV viruses, but these still remain a small minority among those headed for clinical trials.

When it came to the next generation of vaccines, aimed at stimulating cellular immunity, it was already apparent, for example, that different regions of the gag gene were dominant in shaping immune responses, when comparing subtype B and subtype C variants of HIV-1. The former had most response from the p17 region and the latter from the p24 region.

The recombination seen among HIV-1 subtypes and groups in Africa was clearly a major problem but there were for the time being dominant strains on which the first vaccines could be based. He was himself working for a year on sabbatical in Gaborone, Botswana, where a new HIV research institute has been opened in partnership with Harvard, to support that country's expansion of treatment access and commitment to preventive vaccine trials.

Treatment for HIV-2

Dr Emmanuel Bissagnene from Cote d'Ivoire reported on Monday on experience in treating HIV-2 positive people with HAART. While there had been two reports from Europe in this area, he said this was the first such report from Africa.

In the presentation, 18 patients were reported on although the abstract refers to 36 patients, 23 male, 13 female, aged 22 to 67 who had been treated with triple therapy; 27 of whom were treatment naive. In the absence of commercial viral load tests, his group used CD4 responses to monitor treatment. They were able to show that in people who had received prior antiretrovirals, changing all drugs was as important as it was for HIV-1; otherwise there were poor responses in pre-treated patients. One who had been pre-treated with d4T and ddI responded particularly poorly to efavirenz/AZT/3TC, although why efavirenz was ever given may have got lost in in the otherwise excellent simultaneous translation. Their choice for first line treatment was either Trizivir (abacavir, AZT, 3TC) or a protease inhibitor (nelfinavir) with AZT and 3TC and they reported 93% survival at 16 months compared to 45% not on ARVs.

Two viruses, yet again, worse than one

On Wednesday, Dr Abraham Alabi from the UK MRC unit in the Gambia reported a follow-up study of adults recruited betzeen June 1991 and 30 September 1997 from an STD clinic, recruited into a cohort followed up until 31 December 2000. 119 people were living with HIV-1; 137 with HIV-2; 81 with both viruses. CD4 percentage was lowest in the dually infected group and went down with increasing HIV-1 viral load. Those living with HIV-2 had longest survival, those with dual infection the highest death rates over time.

References

Alabi A et al. Viral load; CD4% and survival in HIV monotypic and dual infections in west Africa. Abstract 12DT4-6, 12th ICASA, Ouagadougou, 2001.

Bissagnene E et al. Evaluation du traitement antiretroviral chez les patients VIH-2 positifs à Abidjan. Abstract 10DT3-6, 12th ICASA, Ouagadougou, 2001.