High GUD Incidence in the Early 20 Century Created a Particularly Permissive Time Window for the Origin and Initial Spread of Epidemic HIV Strains

Laboratory for Clinical and Evolutionary Virology, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium.
PLoS ONE (Impact Factor: 3.23). 04/2010; 5(4):e9936. DOI: 10.1371/journal.pone.0009936
Source: PubMed

ABSTRACT The processes that permitted a few SIV strains to emerge epidemically as HIV groups remain elusive. Paradigmatic theories propose factors that may have facilitated adaptation to the human host (e.g., unsafe injections), none of which provide a coherent explanation for the timing, geographical origin, and scarcity of epidemic HIV strains. Our updated molecular clock analyses established relatively narrow time intervals (roughly 1880-1940) for major SIV transfers to humans. Factors that could favor HIV emergence in this time frame may have been genital ulcer disease (GUD), resulting in high HIV-1 transmissibility (4-43%), largely exceeding parenteral transmissibility; lack of male circumcision increasing male HIV infection risk; and gender-skewed city growth increasing sexual promiscuity. We surveyed colonial medical literature reporting incidences of GUD for the relevant regions, concentrating on cities, suffering less reporting biases than rural areas. Coinciding in time with the origin of the major HIV groups, colonial cities showed intense GUD outbreaks with incidences 1.5-2.5 orders of magnitude higher than in mid 20(th) century. We surveyed ethnographic literature, and concluded that male circumcision frequencies were lower in early 20(th) century than nowadays, with low rates correlating spatially with the emergence of HIV groups. We developed computer simulations to model the early spread of HIV-1 group M in Kinshasa before, during and after the estimated origin of the virus, using parameters derived from the colonial literature. These confirmed that the early 20(th) century was particularly permissive for the emergence of HIV by heterosexual transmission. The strongest potential facilitating factor was high GUD levels. Remarkably, the direct effects of city population size and circumcision frequency seemed relatively small. Our results suggest that intense GUD in promiscuous urban communities was the main factor driving HIV emergence. Low circumcision rates may have played a role, probably by their indirect effects on GUD.

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Available from: Viktor Müller, Sep 26, 2015
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    • "We hypothesized that the virus may also have repeatedly crossed the species barrier into local human populations before the current pandemic began. Simulation studies have suggested that SIV would be unlikely to have generated persistent outbreaks in humans in Central Africa before the appearance of large cities during the colonial era [17]. Additionally, it is possible that outbreaks prior to the current pandemic would have been extinguished due to the quick susceptibility of immunodeficient individuals to formerly pervasive infectious diseases (e.g., smallpox). "
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    ABSTRACT: Background HIV-1 derives from multiple independent transfers of simian immunodeficiency virus (SIV) strains from chimpanzees to human populations. We hypothesized that human populations in west central Africa may have been exposed to SIV prior to the pandemic, and that previous outbreaks may have selected for genetic resistance to immunodeficiency viruses. To test this hypothesis, we examined the genomes of Biaka Western Pygmies, who historically resided in communities within the geographic range of the central African chimpanzee subspecies (Pan troglodytes troglodytes) that carries strains of SIV ancestral to HIV-1. Results SNP genotypes of the Biaka were compared to those of African human populations who historically resided outside the range of P. t. troglodytes, including the Mbuti Eastern Pygmies. Genomic regions showing signatures of selection were compared to the genomic locations of genes reported to be associated with HIV infection or pathogenesis. In the Biaka, a strong signal of selection was detected at CUL5, which codes for a component of the vif-mediated APOBEC3 degradation pathway. A CUL5 allele protective against AIDS progression was fixed in the Biaka. A signal of selection was detected at TRIM5, which codes for an HIV post-entry restriction factor. A protective mis-sense mutation in TRIM5 had the highest frequency in Biaka compared to other African populations, as did a protective allele for APOBEC3G, which codes for an anti-HIV-1 restriction factor. Alleles protective against HIV-1 for APOBEC3H, CXCR6 and HLA-C were at higher frequencies in the Biaka than in the Mbuti. Biaka genomes showed a strong signal of selection at TSG101, an inhibitor of HIV-1 viral budding. Conclusions We found protective alleles or evidence for selection in the Biaka at a number of genes associated with HIV-1 infection or progression. Pygmies have also been reported to carry genotypes protective against HIV-1 for the genes CCR5 and CCL3L1. Our hypothesis that HIV-1 may have shaped the genomes of some human populations in West Central Africa appears to merit further investigation.
    BMC Evolutionary Biology 12/2012; 12(1):237. DOI:10.1186/1471-2148-12-237 · 3.37 Impact Factor
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    • "On the other hand, not all SIV strains in Africa are closely related to posterior epidemic HIV strains. It was recently found that several GUD (Genital Ulcers Diseases, like syphilis, chancroid and lymphogranuloma venereum), prostitution and possibly lack of circumcision in African human populations, could have favoured the jump of species barrier or host-shift of SIV from monkeys to humans [74]. "
    Epidemiology - Current Perspectives on Research and Practice, 03/2012; , ISBN: 978-953-51-0382-0
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    • "Yet none of these countries, where most men are circumcised [69], have had adult prevalence rates as high as those observed in eastern and southern Africa [22,39]. Hence, it could be reasonably concluded that structural features of wealth and poverty patterning behaviour [41], reported practice of multiple and concurrent partnerships [49,52], couple discordancy [124], prevalence of other STIs [40,42,44] and geographic variations in MC [69,94] have synergized to provide the "perfect storm" for the HIV epidemic in sub-Saharan African countries with low MC prevalence [43,91]. "
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    ABSTRACT: Heterosexual exposure accounts for most HIV transmission in sub-Saharan Africa, and this mode, as a proportion of new infections, is escalating globally. The scientific evidence accumulated over more than 20 years shows that among the strategies advocated during this period for HIV prevention, male circumcision is one of, if not, the most efficacious epidemiologically, as well as cost-wise. Despite this, and recommendation of the procedure by global policy makers, national implementation has been slow. Additionally, some are not convinced of the protective effect of male circumcision and there are also reports, unsupported by evidence, that non-sex-related drivers play a major role in HIV transmission in sub-Saharan Africa. Here, we provide a critical evaluation of the state of the current evidence for male circumcision in reducing HIV infection in light of established transmission drivers, provide an update on programmes now in place in this region, and explain why policies based on established scientific evidence should be prioritized. We conclude that the evidence supports the need to accelerate the implementation of medical male circumcision programmes for HIV prevention in generalized heterosexual epidemics, as well as in countering the growing heterosexual transmission in countries where HIV prevalence is presently low.
    Journal of the International AIDS Society 10/2011; 14(1):49. DOI:10.1186/1758-2652-14-49 · 5.09 Impact Factor
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