To the Editor:
The early spread of HIV within Canada,1,2 the United States,3,4 and Western Europe 5,6 was the result of HIV-1, Group M, Subtype B infection, and it occurred mainly within the men who have sex with men and then the intravenous drug use (IDU) communities. The majority of the knowledge and experience with diagnosis, natural history, and treatment of HIV is based on Subtype B virus as a result of the initial spread of the HIV pandemic in these two populations. Although Subtype B accounts for only approximately 10% of global HIV infections,7 it still remains the dominant viral strain seen in North America.8 Worldwide, Subtype C accounts for approximately half of currently infected individuals, the majority of new HIV-1 infections, and is seen most often in heterosexuals.7
Non-B subtype infections are almost exclusively seen in developed countries in migrants from the developing world, most often Africa.9 Recent reports from the United States,10-13 Europe,14-17 South America,18 Asia,19,20 and Canada21 have all highlighted the increasing global genetic diversity of HIV-1 subtypes. However, transmission of these non -B subtypes, outside the traditional risk groups defined by country of origin for that subtype, have seldom been reported.15
The Canadian experience is different from the United States in that Canadian immigration policies have not specifically excluded all HIV-infected applicants from immigration to Canada.22,23 As such, Canada is already through migration seeing significant HIV diversity with an increasing proportion of non-B subtypes.21,24
Following viral diversity is important because differences between subtypes have been reported in transmissibility,25 disease pathogenesis,26 progression,27 and speed of progression to AIDS-defining illnesses,28-30 accuracy of viral load monitoring by conventional assays,31 and response to treatment.32,33 As data continue to emerge that all HIV-1 subtypes cannot automatically be considered equivalent, it will become increasingly important to identify non-B subtype infections.34 As immigration policies have shifted in the United States toward more open policies, the prevalence of non-B subtypes can only be expected now to increase in all developed countries.
We wanted to discover if Canadian-born patients with HIV are still exclusively infected with Subtype B and immigrant and refugee populations, especially from Africa, are still exclusively infected with non-B subtypes. We reviewed all individuals receiving care at the regional HIV program for southern Alberta (SAC) for HIV subtype, country of birth, and risk activities (including travel) for HIV infection. Data were collected through a database review and subsequent chart review of SAC medical records. The SAC cohort dates back to 1984 with ongoing rolling recruitment, and administrative data use has been reviewed and approved by the Conjoint Health Research Ethics Board, University of Calgary.
A total of 3341 patients have been seen at SAC since 1984. A total of 1050 patients have a known subtype, country of birth, travel, and HIV risk activity well documented.
We identified 24 Canadian-born patients with a non-B HIV-1 infection (Table 1, Part 1). This represents 3% (24 of 714) of Canadian- born patients with HIV with a known subtype. The median age at diagnosis was 33 years, 62.5% (15 of 24) were women, and 83% (20 of 24) identified only heterosexual intercourse as their HIV risk. Eight (26%) patients were nonwhite and seven identified themselves as being Aboriginal. The most common HIV-1 subtype was C, with 58% (14 of 24) followed by two of each Subtype A1, AG, CRF01_AE, G, and D. Although two patients reported unprotected sexual activity outside North America, 22 patients reported no travel outside Canada. Four of these 24 patients (16%) reported a history of IDU, three (12%) had been incarcerated, and six (25%) identified a sexual contact with immediate links to an endemic area.
We also identified 10 of 208 (5%) African-born patients with a known subtype as having Subtype B infection (Table 1, Part 2). The median age of these patients at diagnosis was 35 years, 30% (three of 10) were women, and 90% (nine of 10) identified themselves as infected by unprotected heterosexual activity. One patient reported a history of IDU and two patients (20%) also reported a history of blood transfusions while in Africa.
The extent of viral diversity reported is likely an under estimate because genotyping has only been done routinely since 2005 for antiretroviral treatment-naïve patients. We had previously assumed that risk factors for acquisition of a non-B subtype virus was primarily immigration from an endemic area and/or travel with risk activities in such areas.35 We have found that Canadian-born patients are increasingly infected with a non-B virus without travel exposure and such infections are most frequently seen in heterosexual women. Conversely, some patients, predominantly men from endemic areas of non-B HIV infection in Africa, have HIV-1 Subtype B infection presumably acquired in Canada.
Biologic characteristics of some subtypes might explain the non-B prevalence in our group.25 Vaginal compared with anal intercourse may carry an increased risk for non-B HIV-1 transmission.25,36 Although Aboriginal patients in our study were disproportionately affected with non-B HIV-1 infection, we suspect this is a reflection of socioeconomic disadvantages and concomitant risk factors rather than the result of a biologic explanation.37 Although IDU remains a high-risk group for new HIV-1 infection in Canada, non-B HIV-1 subtypes do not appear so far to have been introduced locally into this community.
Our data suggest that traditional assumptions are no longer sufficient to predict the occurrence of non-B HIV-1 infection in developed countries. Migration, travel, as well as in-country transmission will continue to feed local viral diversity. Attention to measuring subtype will become increasingly important as the clinical and epidemiologic differences between subtypes continue to be explored.
LeeAnne M. Luft, MD
Brenda Beckthold, BSc
M. John Gill, MB, ChB
Department of Medicine, University of Calgary, Calgary, Alberta, Canada
1. Health Canada. HIV and AIDS in Canada. Minister of Public Works and Government Services. Ottawa, Ontario, Canada: Surveillance Report to June 30, 2002. Ottawa, ON: The Canadian HIV/AIDS Clearinghouse; 2002.
2. Ottawa: Health Canada. Summary: Estimates of HIV Prevalence and Incidence in Canada, 2008. Ottawa, ON: Public Health Agency of Canada; 2008.
3. Osborn JE. HIV: the more things change, the more they stay the same. Public Health Agency of Canada. Tunney's Pasture, Ottawa, Ontario, Canada: Nat Med. 1995;1:991-993.
4. de Oliveira CF, Diaz RS, Machado DM, et al. Surveillance of HIV-1 genetic subtypes and diversity in the US blood supply. Transfusion. 2000;40:1399-1406.
5. Glauser MP, Francioli P. Clinical and epidemiological survey of acquired immune deficiency syndrome in Europe. Eur J Clin Microbiol. 1984;3:55-58.
6. Casado C, Urtasun I, Saragosti S, et al. Different distribution of HIV type 1 genetic variants in European patients with distinct risk practices. AIDS Res Hum Retroviruses. 2000;16:299-304.
7. Hemelaar J, Gouws E, Ghys PD, et al. Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004. AIDS. 2006;20:W13-W23.
8. Yang C, Pieniazek D, Owen SM, et al. Detection of phylogenetically diverse human immunodeficiency virus type 1 groups M and O from plasma by using highly sensitive and specific generic primers. J Clin Microbiol. 1999;37:2581-2586.
9. Thomson MM, Najera R. Increasing HIV-1 genetic diversity in Europe. J Infect Dis. 2007;196:1120-1124.
10. Wheeler WH, Ziebell RA, Zabina H, et al. Prevalence of transmitted drug resistance associated mutations and HIV-1 subtypes in new HIV-1 diagnoses, US—2006. AIDS. 2010;24:1203-1212.
11. Sides TL, Akinsete O, Henry K, et al. HIV-1 subtype diversity in Minnesota. J Infect Dis. 2005;192:37-45.
12. Cartwright CP. The changing epidemiology of HIV/AIDS at a Minnesota hospital: impact of demographic change and viral diversity. J Med Virol. 2006;78(suppl 1):S19-S21.
13. Parker MM, Gordon D, Reilly A, et al. Prevalence of drug-resistant and nonsubtype B HIV strains in antiretroviral-naive, HIV-infected individuals in New York State. AIDS Patient Care STDS. 2007;21:644-652.
14. Descamps D, Chaix ML, Montes B, et al. Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France. J Antimicrob Chemother. 2010;65:2620-2627.
15. Burns FM, Arthur G, Johnson AM, et al. United Kingdom acquisition of HIV infection in African residents in London: more than previously thought. AIDS. 2009;23:262-266.
16. Parczewski M, Leszczyszyn-Pynka M, Bander D, et al. Characteristics of HIV-1 non-B subtype infections in Northwest Poland. J Med Virol. 2010;82:1306-1313.
17. Habekova M, Takacova M, Lysy J, et al. Genetic subtypes of HIV type 1 circulating in Slovakia. AIDS Res Hum Retroviruses. 2010;26:1103-1107.
18. Toledo PV, de Carvalho DS, de Rossi SG, et al. Genetic diversity of human immunodeficiency virus-1 isolates in Parana, Brazil. Braz J Infect Dis. 2010;14:230-236.
19. Tan Y, Chan D, Chan D, et al. High genetic diversity of HIV-1 viruses in Macao, China. J Infect. 2010;61:164-172.
20. Chen JH, Wong KH, Chen Z, et al. Increased genetic diversity of HIV-1 circulating in Hong Kong. PLoS ONE. 2010;5:e12198.
21. Krentz H, Gill MJ. The five-year impact of an evolving global epidemic, changing migration patterns, and policy changes in a regional Canadian HIV population. Health Policy. 2009;90:296-302.
22. Osuna JP. The exclusion from the United States of aliens infected with the AIDS virus: recent developments and prospects for the future. Houst J Int Law. 1993;16:1-41.
23. Fairchild AL, Tynan EA. Policies of containment: immigration in the era of AIDS. Am J Public Health. 1994;84:2011-2022.
24. Bennett D. HIV [corrected] genetic diversity surveillance in the United States. J Infect Dis. 2005;192:4-9.
25. John-Stewart GC, Nduati RW, Rousseau CM, et al. Subtype C Is associated with increased vaginal shedding of HIV-1. J Infect Dis. 2005;192:492-496.
26. Rao VR, Sas AR, Eugenin EA, et al. HIV-1 clade-specific differences in the induction of neuropathogenesis. J Neurosci. 2008;28:10010-10016.
27. Kuritzkes DR. HIV-1 subtype as a determinant of disease progression. J Infect Dis. 2008;197:638-639.
28. Keller M, Lu Y, Lalonde RG, et al. Impact of HIV-1 viral subtype on CD4+ T-cell decline and clinical outcomes in antiretroviral naive patients receiving universal healthcare. AIDS. 2009;23:731-737.
29. Church JD, Huang W, Mwatha A, et al. HIV-1 tropism and survival in vertically infected Ugandan infants. J Infect Dis. 2008;197:1382-1388.
30. Baeten JM, Chohan B, Lavreys L, et al. 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. 2007;195:1177-1180.
31. Church D, Gregson D, Lloyd T, et al. HIV-1 viral load multi-assay comparison of the RealTime HIV-1, COBAS TaqMan 48 v 1.0, Easy Q v1.2 and Versant v3.0 assays in a cohort of Canadian patients with diverse HIV subtype infections. J Clin Microbiol. 2011;49:118-124.
32. Easterbrook PJ, Smith M, Mullen J, et al. Impact of HIV01 viral subtype on disease progression and response to antiretroviral therapy. J Int AIDS Soc. 2010;13:4.
33. Geretti AM, Harrison L, Green H, et al. Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy. Clin Infect Dis. 2009;48:1296-2305.
34. Campbell TB. Are all HIV type 1 strains created equal? Clin Infect Dis. 2006;42:853-854.
35. Thomson MM, Najera R. Travel and the introduction of human immunodeficiency virus type 1 non-B subtype genetic forms into Western countries. Clin Infect Dis. 2001;32:1732-1737.
36. Dias CF, Nunes CC, Freitas IO, et al. High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naive patients in Porto Alegre, RS, Brazil. Rev Inst Med Trop Sao Paulo. 2009;51:191-196.
37. Duncan KC, Reading C, Borwein AM, et al. HIV incidence and prevalence among Aboriginal peoples in Canada. AIDS Behav. 2011;15:214-227.
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