Evolution and molecular epidemiology of subtype C HIV-1 in Zimbabwe

Abstract

Objective To investigate the origins and evolutionary history of subtype C HIV-1 in Zimbabwe in a context of regional conflict and migration. Design HIV-1C pol sequence datasets were generated from four sequential cohorts of antenatal women in Harare, Zimbabwe sampled over 15 years (1991–2006). Methods One hundred and seventy-seven HIV-1C pol sequences were obtained from four successive cohorts in Zimbabwe. Maximum-likelihood methods were used to explore phylogenetic relationships between Zimbabwean HIV-1C sequences and subtype C strains from other regions. A Bayesian coalescent-based framework was used to estimate evolutionary parameters for HIV-1C in Zimbabwe, including origin and demographic growth patterns. Results Zimbabwe HIV-1C pol demonstrated increasing sequence divergence over the 15-year period. Nearly all Zimbabwe sequences clustered phylogenetically with subtype C strains from neighboring countries. Bayesian evolutionary analysis indicated a most recent common ancestor date of 1973 with three epidemic growth phases: an initial slow phase (1970s) followed by exponential growth (1980s), and a linearly expanding epidemic to the present. Bayesian trees provided evidence for multiple HIV-1C introductions into Zimbabwe during 1979–1981, corresponding with Zimbabwean national independence following a period of socio-political instability. Conclusion The Zimbabwean HIV-1C epidemic likely originated from multiple introductions in the late 1970s and grew exponentially during the 1980s, corresponding to changing political boundaries and rapid population influx from neighboring countries. The timing and phylogenetic clustering of the Zimbabwean sequences is consistent with an origin in southern Africa and subsequent expansion. HIV-1 sequence data contain important epidemiological information, which can help focus treatment and prevention strategies in light of more recent political volatility in Zimbabwe.

Phylogenetic Studies of Transmission Dynamics in Generalized HIV Epidemics

“…13,66–74 These analyses can contribute to the design of intervention strategies through better understanding of epidemic growth potential, or factors contributing to historical geographic spread of subtypes or recombinants. Phylogeographic approaches showed that HIV-1C in Zimbabwe expanded through multiple introductions originating in southern Africa and localized exponential growth in the 1980s corresponding to demographic and political change.…”

HIV Non-B Subtype Distribution: Emerging Trends and Risk Factors for Imported and Local Infections Newly Diagnosed in South Australia

“…We note that further subtype validation should be conducted with alternative HIV genes, such as env. 37 Ongoing surveillance and a deeper understanding of HIV variation, including factors and molecular mechanisms that affect transmission, replication, and resistance, are crucial for the development of appropriately targeted subtype-specific prevention and treatment options for populations most at risk. 5,9,21,29 Further evidence of subtype differences could drastically change the way we respond to the HIV epidemic.…”

HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission

“…However, a combination of other factors may be as likely to contribute to the swift growth of HIV-1 subtype C. A founder effect, which has been hypothesized to explain the dominance of specific subtypes throughout Africa, could be relevant 31, 32 . Additionally, Tatem et al recently provided evidence to suggest that regions with greater accessibility allowing for increased mobility, such as in southern Africa, are associated with clusters of similar subtypes throughout the transportation infrastructure 33 .…”

“…Another potential explanation is that subtype C has shown lower viral fitness, and therefore may result in slower disease progression compared to other subtypes 11, 34–36 ; individuals with a slower progressing disease not only add person-years to prevalence estimates, but also have more opportunity to transmit their infection over a longer period of time. Finally, subtype C may be more prevalent in sexual networks with behavioral and demographic characteristics leading to higher risk for HIV-1 transmission 31, 37, 38 .…”