1887

Abstract

HIV prevalence has decreased in Uganda since the 1990s, but remains substantial within high-risk groups. Here, we reconstruct the history and spread of HIV subtypes A1 and D in Uganda and explore the transmission dynamics in high-risk populations. We analysed HIV sequences from female sex workers in Kampala ( = 42), Lake Victoria fisher-folk ( = 46) and a rural clinical cohort ( = 74), together with publicly available sequences from adjacent regions in Uganda ( = 412) and newly generated sequences from samples taken in Kampala in 1986 ( = 12). Of the sequences from the three Ugandan populations, 60 (37.1 %) were classified as subtype D, 54 (33.3 %) as subtype A1, 31 (19.1 %) as A1/D recombinants, six (3.7 %) as subtype C, one (0.6 %) as subtype G and 10 (6.2 %) as other recombinants. Among the A1/D recombinants we identified a new candidate circulating recombinant form. Phylodynamic and phylogeographic analyses using BEAST indicated that the Ugandan epidemics originated in 1960 (1950–1968) for subtype A1 and 1973 (1970–1977) for D, in rural south-western Uganda with subsequent spread to Kampala. They also showed extensive interconnection with adjacent countries. The sequence analysis shows both epidemics grew exponentially during the 1970s–1980s and decreased from 1992, which agrees with HIV prevalence reports in Uganda. Inclusion of sequences from the 1980s indicated the origin of both epidemics was more recent than expected and substantially narrowed the confidence intervals in comparison to previous estimates. We identified three transmission clusters and ten pairs, none of them including patients from different populations, suggesting active transmission within a structured transmission network.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.000107
2015-07-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/7/1890.html?itemId=/content/journal/jgv/10.1099/vir.0.000107&mimeType=html&fmt=ahah

References

  1. Abecasis A. B., Vandamme A. M., Lemey P.(2009). Quantifying differences in the tempo of human immunodeficiency virus type 1 subtype evolution. J Virol 83, 1291712924. [View Article][PubMed] [Google Scholar]
  2. Asiki G., Mpendo J., Abaasa A., Agaba C., Nanvubya A., Nielsen L., Seeley J., Kaleebu P., Grosskurth H., Kamali A.(2011). HIV and syphilis prevalence and associated risk factors among fishing communities of Lake Victoria, Uganda. Sex Transm Infect 87, 511515. [View Article][PubMed] [Google Scholar]
  3. Baeten J. M., Chohan B., Lavreys L., Chohan V., McClelland R. S., Certain L., Mandaliya K., Jaoko W., Overbaugh J.(2007). HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads. J Infect Dis 195, 11771180. [View Article][PubMed] [Google Scholar]
  4. Cane P.(2011). HIV drug resistance testing. Methods Mol Biol 665, 123132. [View Article][PubMed] [Google Scholar]
  5. Carswell J. W.(1987). HIV infection in healthy persons in Uganda. AIDS 1, 223227.[PubMed] [Google Scholar]
  6. Carswell J. W., Lloyd G.(1987). Rise in prevalence of HIV antibodies recorded at an antenatal booking clinic in Kampala, Uganda. AIDS 1, 192193.[PubMed] [Google Scholar]
  7. Conroy S. A., Laeyendecker O., Redd A. D., Collinson-Streng A., Kong X., Makumbi F., Lutalo T., Sewankambo N., Kiwanuka N. et al.(2010). Changes in the distribution of HIV type 1 subtypes D and A in Rakai District, Uganda between 1994 and 2002. AIDS Res Hum Retroviruses 26, 10871091. [View Article][PubMed] [Google Scholar]
  8. Deng W., Nickle D. C., Learn G. H., Maust B., Mullins J. I.(2007). ViroBLAST: a stand-alone BLAST web server for flexible queries of multiple databases and user’s datasets. Bioinformatics 23, 23342336. [View Article][PubMed] [Google Scholar]
  9. Drummond A. J., Suchard M. A., Xie D., Rambaut A.(2012). Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol Biol Evol 29, 19691973. [View Article][PubMed] [Google Scholar]
  10. Grabowski M. K., Lessler J., Redd A. D., Kagaayi J., Laeyendecker O., Ndyanabo A., Nelson M. I., Cummings D. A., Bwanika J. B. et al.(2014). The role of viral introductions in sustaining community-based HIV epidemics in rural Uganda: evidence from spatial clustering, phylogenetics, and egocentric transmission models. PLoS Med 11, e1001610. [View Article][PubMed] [Google Scholar]
  11. Gray R. R., Tatem A. J., Lamers S., Hou W., Laeyendecker O., Serwadda D., Sewankambo N., Gray R. H., Wawer M. et al.(2009). Spatial phylodynamics of HIV-1 epidemic emergence in east Africa. AIDS 23, F9F17. [View Article][PubMed] [Google Scholar]
  12. Green E. C., Halperin D. T., Nantulya V., Hogle J. A.(2006). Uganda’s HIV prevention success: the role of sexual behavior change and the national response. AIDS Behav 10, 335346, discussion 347–350. [View Article][PubMed] [Google Scholar]
  13. Hué S., Pillay D., Clewley J. P., Pybus O. G.(2005). Genetic analysis reveals the complex structure of HIV-1 transmission within defined risk groups. Proc Natl Acad Sci U S A 102, 44254429. [View Article][PubMed] [Google Scholar]
  14. Kaleebu P., French N., Mahe C., Yirrell D., Watera C., Lyagoba F., Nakiyingi J., Rutebemberwa A., Morgan D. et al.(2002). Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda. J Infect Dis 185, 12441250. [View Article][PubMed] [Google Scholar]
  15. Keele B. F., Van Heuverswyn F., Li Y., Bailes E., Takehisa J., Santiago M. L., Bibollet-Ruche F., Chen Y., Wain L. V. et al.(2006). Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science 313, 523526. [View Article][PubMed] [Google Scholar]
  16. Kiwanuka N., Laeyendecker O., Robb M., Kigozi G., Arroyo M., McCutchan F., Eller L. A., Eller M., Makumbi F. et al.(2008). Effect of human immunodeficiency virus Type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection. J Infect Dis 197, 707713. [View Article][PubMed] [Google Scholar]
  17. Kiwanuka N., Laeyendecker O., Quinn T. C., Wawer M. J., Shepherd J., Robb M., Kigozi G., Kagaayi J., Serwadda D. et al.(2009). HIV-1 subtypes and differences in heterosexual HIV transmission among HIV-discordant couples in Rakai, Uganda. AIDS 23, 24792484. [View Article][PubMed] [Google Scholar]
  18. Korber B., Muldoon M., Theiler J., Gao F., Gupta R., Lapedes A., Hahn B. H., Wolinsky S., Bhattacharya T.(2000). Timing the ancestor of the HIV-1 pandemic strains. Science 288, 17891796. [View Article][PubMed] [Google Scholar]
  19. Kosakovsky Pond S. L., Posada D., Stawiski E., Chappey C., Poon A. F., Hughes G., Fearnhill E., Gravenor M. B., Leigh Brown A. J., Frost S. D.(2009). An evolutionary model-based algorithm for accurate phylogenetic breakpoint mapping and subtype prediction in HIV-1. PLOS Comput Biol 5, e1000581. [View Article][PubMed] [Google Scholar]
  20. LANL (2014a). HIV circulating recombinant forms (CRFs). http://www.hiv.lanl.gov/content/sequence/HIV/CRFs/CRFs.html.
  21. LANL (2014b). Los Alamos HIV database. http://www.hiv.lanl.gov.
  22. Leigh Brown A. J., Lycett S. J., Weinert L., Hughes G. J., Fearnhill E., Dunn D. T.UK HIV Drug Resistance Collaboration(2011). Transmission network parameters estimated from HIV sequences for a nationwide epidemic. J Infect Dis 204, 14631469. [View Article][PubMed] [Google Scholar]
  23. Lemey P., Rambaut A., Drummond A. J., Suchard M. A.(2009). Bayesian phylogeography finds its roots. PLOS Comput Biol 5, e1000520. [View Article][PubMed] [Google Scholar]
  24. Maljkovic Berry I., Ribeiro R., Kothari M., Athreya G., Daniels M., Lee H. Y., Bruno W., Leitner T.(2007). Unequal evolutionary rates in the human immunodeficiency virus type 1 (HIV-1) pandemic: the evolutionary rate of HIV-1 slows down when the epidemic rate increases. J Virol 81, 1062510635. [View Article][PubMed] [Google Scholar]
  25. McCormack G. P., Glynn J. R., Crampin A. C., Sibande F., Mulawa D., Bliss L., Broadbent P., Abarca K., Pönnighaus J. M. et al.(2002). Early evolution of the human immunodeficiency virus type 1 subtype C epidemic in rural Malawi. J Virol 76, 1289012899. [View Article][PubMed] [Google Scholar]
  26. Minin V. N., Bloomquist E. W., Suchard M. A.(2008). Smooth skyride through a rough skyline: Bayesian coalescent-based inference of population dynamics. Mol Biol Evol 25, 14591471. [View Article][PubMed] [Google Scholar]
  27. Nazziwa J., Njai H. F., Ndembi N., Birungi J., Lyagoba F., Gershim A., Nakiyingi-Miiro J., Nielsen L., Mpendo J. et al.(2013). Short communication: HIV type 1 transmitted drug resistance and evidence of transmission clusters among recently infected antiretroviral-naive individuals from Ugandan fishing communities of Lake Victoria. AIDS Res Hum Retroviruses 29, 788795. [View Article][PubMed] [Google Scholar]
  28. Nsubuga R. N., Maher D., Todd J. E.(2013). Impact of antiretroviral therapy on adult HIV prevalence in a low-income rural setting in Uganda: a longitudinal population-based study. J Acquir Immune Defic Syndr 62, 562568. [View Article][PubMed] [Google Scholar]
  29. Pickering H., Okongo M., Ojwiya A., Yirrell D., Whitworth J.(1997). Sexual networks in Uganda: mixing patterns between a trading town, its rural hinterland and a nearby fishing village. Int J STD AIDS 8, 495500. [View Article][PubMed] [Google Scholar]
  30. Price M. N., Dehal P. S., Arkin A. P.(2010). FastTree 2–approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490. [View Article][PubMed] [Google Scholar]
  31. Ragonnet-Cronin M., Hodcroft E., Hué S., Fearnhill E., Delpech V., Brown A. J., Lycett S.UK HIV Drug Resistance Database(2013). Automated analysis of phylogenetic clusters. BMC Bioinformatics 14, 317. [View Article][PubMed] [Google Scholar]
  32. Serwadda D., Mugerwa R. D., Sewankambo N. K., Lwegaba A., Carswell J. W., Kirya G. B., Bayley A. C., Downing R. G., Tedder R. S. et al.(1985). Slim disease: a new disease in Uganda and its association with HTLV-III infection. Lancet 2, 849852. [View Article][PubMed] [Google Scholar]
  33. Shapiro B., Rambaut A., Drummond A. J.(2006). Choosing appropriate substitution models for the phylogenetic analysis of protein-coding sequences. Mol Biol Evol 23, 79. [View Article][PubMed] [Google Scholar]
  34. Ssemwanga D., Kapaata A., Lyagoba F., Magambo B., Nanyonjo M., Mayanja B. N., Parry C. M., Kaleebu P.(2012a). Low drug resistance levels among drug-naive individuals with recent HIV type 1 infection in a rural clinical cohort in southwestern Uganda. AIDS Res Hum Retroviruses 28, 17841787. [View Article][PubMed] [Google Scholar]
  35. Ssemwanga D., Ndembi N., Lyagoba F., Bukenya J., Seeley J., Vandepitte J., Grosskurth H., Kaleebu P.(2012b). HIV type 1 subtype distribution, multiple infections, sexual networks, and partnership histories in female sex workers in Kampala, Uganda. AIDS Res Hum Retroviruses 28, 357365. [View Article][PubMed] [Google Scholar]
  36. Stamatakis A., Hoover P., Rougemont J.(2008). A rapid bootstrap algorithm for the RAxML Web servers. Syst Biol 57, 758771. [View Article][PubMed] [Google Scholar]
  37. Stoneburner R. L., Low-Beer D.(2004). Population-level HIV declines and behavioral risk avoidance in Uganda. Science 304, 714718. [View Article][PubMed] [Google Scholar]
  38. Uganda AIDS Commission (2012). Uganda national progress report. http://www.unaids.org/en/regionscountries/countries/uganda/.
  39. UNAIDS (2013). Report on the global AIDS epidemic. http://www.unaids.org.
  40. Vandepitte J., Bukenya J., Weiss H. A., Nakubulwa S., Francis S. C., Hughes P., Hayes R., Grosskurth H.(2011). HIV and other sexually transmitted infections in a cohort of women involved in high-risk sexual behavior in Kampala, Uganda. Sex Transm Dis 38, 316323.[PubMed] [Google Scholar]
  41. Vidal N., Peeters M., Mulanga-Kabeya C., Nzilambi N., Robertson D., Ilunga W., Sema H., Tshimanga K., Bongo B., Delaporte E.(2000). Unprecedented degree of human immunodeficiency virus type 1 (HIV-1) group M genetic diversity in the Democratic Republic of Congo suggests that the HIV-1 pandemic originated in Central Africa. J Virol 74, 1049810507. [View Article][PubMed] [Google Scholar]
  42. Volz E. M., Koelle K., Bedford T.(2013). Viral phylodynamics. PLOS Comput Biol 9, e1002947. [View Article][PubMed] [Google Scholar]
  43. Wertheim J. O., Fourment M., Kosakovsky Pond S. L.(2012). Inconsistencies in estimating the age of HIV-1 subtypes due to heterotachy. Mol Biol Evol 29, 451456. [View Article][PubMed] [Google Scholar]
  44. Worobey M., Gemmel M., Teuwen D. E., Haselkorn T., Kunstman K., Bunce M., Muyembe J. J., Kabongo J. M., Kalengayi R. M. et al.(2008). Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960. Nature 455, 661664. [View Article][PubMed] [Google Scholar]
  45. Yirrell D. L., Pickering H., Palmarini G., Hamilton L., Rutemberwa A., Biryahwaho B., Whitworth J., Brown A. J.(1998). Molecular epidemiological analysis of HIV in sexual networks in Uganda. AIDS 12, 285290. [View Article][PubMed] [Google Scholar]
  46. Yirrell D. L., Kaleebu P., Morgan D., Hutchinson S., Whitworth J. A.(2004). HIV-1 subtype dynamics over 10 years in a rural Ugandan cohort. Int J STD AIDS 15, 103106. [View Article][PubMed] [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.000107
Loading
/content/journal/jgv/10.1099/vir.0.000107
Loading

Data & Media loading...

Supplements

Supplementary Data



PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error