HIV-1 Strain Surveillance in Canada

HIV/AIDS Epi Updates

At A Glance

The Canadian HIV Strain and Drug Resistance Program continues to monitor and assess HIV strains and the transmission of drug resistance in Canada.

Although HIV-1 subtype B continues to predominate, subtypes A, C, D, E, and the circulating recombinants A/B, A/C, and A/G have been identified in Canada.

The overall prevalence of non-B HIV-1 subtypes is 6.9%.

Preliminary assessments of HIV-1 strains among newly diagnosed, treatment naïve individuals in Canada suggest:

Significantly higher proportions of non-B HIV-1 infections among females (compared to males), among persons reporting heterosexual contact as their primary exposure factor, and among persons of Black, Asian, or mixed ethnicities.

Geographic variation in the prevalence of HIV-1 subtypes, likely related to travel and migration from countries where divergent HIV strains predominate.

April 2003

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HIV-1 Strain Surveillance in Canada

Two types of HIV have been characterized in humans, HIV-1 and HIV-2. Both HIV-1 and HIV-2 can lead to AIDS. HIV-2 is less common than HIV-1 and is mainly found in West Africa.  HIV-1 can be divided into three major groups: "M" (major), "O" (outlier) and "N" (new).¹ The vast majority of isolates cluster in the "M" group. Distinct lineages within Group M have also been identified. These include subtype designations A to E (subtype E is also referred to CRF01_AE (the circulating recombinant form, CRF A/E)), F to H, J, and K.² HIV-1 subtypes A and C are the most common, accounting for about one-half of HIV-1 infections world-wide. In Canada, the United States and Western Europe, HIV-1 subtype B predominates. However, due to travel and migration, non-B subtypes are increasingly being reported in these parts of the world.

This Epi Update describes why surveillance of HIV strains is important, and provides a summary of the surveillance of HIV strains in Canada and the prevalence of divergent HIV strains in the United States, and Western Europe.

Why conduct HIV strain surveillance?

The Canadian HIV Strain and Drug Resistance Surveillance Program (CHSDRSP) was initiated as an integrated group of projects aimed at enhancing the national surveillance of HIV. Through a collaborative approach between the provinces, territories, and Health Canada, laboratory samples (serum from newly diagnosed HIV-positive individuals) and corresponding epidemiological data are sent from the Provincial Health Laboratories to Health Canada for HIV strain and drug resistance testing. The results are shared with key stakeholders including the provinces and territories, when completed. One of the central goals of this program is to conduct the systematic surveillance of HIV subtypes in Canada in order to attain the following four main objectives:

1. Improve HIV diagnostics and screening strategies
   The broad genetic diversity of HIV has implications for the ability of diagnostic tests to reliably detect circulating HIV strains.^3,4 The sentinel arm of the CHSDRSP, through the reference services of the National HIV Laboratories, addresses this goal by testing samples with unusual test results. Based on the knowledge of circulating HIV strains, modifications can be made in current tests to ensure that all HIV positive persons are detected upon testing. This is also relevant for ensuring the safety of the blood supply since the tests used for screening donated blood should be able to detect circulating HIV variants.             

2. Inform vaccine development
   It is important to know the distribution of the viral subtypes and intrasubtype variation to target vaccine development and testing since the efficacy and effectiveness of vaccines may be subtype-specific.^3,4

3. Assess HIV transmission patterns
   Although genetic analyses have been used to assess the spread of HIV globally^4,5, there is little consensus on whether differences in HIV affect sexual and maternal transmission rates.^6-9 Some studies note differences in the biological properties of HIV-1 subtypes^10-12, however, this needs to be confirmed. Knowing the distribution of HIV variants in Canada, along with corresponding epidemiological factors, will help to assess the implications of any differences in transmissibility. The public health implications of such findings, including prevention and treatment strategies, are of special interest.

4. Assess HIV pathogenesis and progression of HIV-related diseases
   Although the rate of HIV-related disease progression is affected by many factors including host factors and evidence suggests that the immunologic responses may be less suppressed by HIV-2 than by HIV-1^13,14, this needs to be clarified. And whereas some studies suggest genetic subtypes play a role in disease progression, other studies suggest the reverse. Many of these studies are reviewed by Hu et al³ and by Tatt et al.⁴ This area needs further investigation.

Distribution of HIV-1 subtypes

Canada:

• Results from the CHSDRSP show that 6.9% of the sampled population (n=1,312) were infected with non-B subtypes (See Table 1 for subtype distribution)¹⁵

Table 1: Distribution of HIV-1 Subtypes

^aThe recombinant A/E has also been referred to as subtype E

• Preliminary results from the CHSDRSP suggest a significant proportion of individuals infected with a non-B HIV-1 subtype are female, African or Asian origin, and/or identify heterosexual sex as their primary risk factor.¹⁵ These correlations are likely due to travel and migration from endemic areas where divergent HIV-1 subtypes predominate and where heterosexual sex is a major risk factor for HIV-1 infection.

• In 1995 HIV-1 subtype A was reported in an African born male who moved to Canada in 1983.¹⁶

• The BC Centre for Excellence in HIV/AIDS has conducted genetic analyses of HIV linked to cohort studies and to the BC HIV drug treatment program. These studies suggest that non-B subtypes in BC represent at least 4% of HIV infections among individuals starting therapy.¹⁷ HIV-1 subtypes A, C, and D have been identified.

• HIV-2 was detected in Canada as early as 1988.¹⁸

Existing studies on high-risk populations suggest that HIV-1 subtype B is the most common subtype found in the country.

• In 1998, serological samples from 31 HIV positive persons of both genders, representing approximately 25% of known HIV positive persons in Newfoundland, were all of HIV-1 subtype B.¹⁹

• In 1999, all HIV-1 sequences analysed among infected injection drug users (n=17) and men who have sex with men (n=5) residing in Montreal²⁰ were of subtype B.

• As of November 2000, all samples of 31 recent seroconverters in the POLARIS cohort in Ontario are of subtype B.²¹

United States:

• As early as 1993, subtype D was reported in the United States.²²

• Results from CDC's ongoing sentinel surveillance of strain and drug resistance has found 1.6% of persons newly diagnosed with HIV were infected with subtype A (n = 321).²³

• In another cohort study of 88 treatment-naive individuals presenting to a Boston hospital in 1999, nine (10%) were infected with non-B HIV-1 (subtypes A, C, and E and the recombinant A/G). All these individuals were born outside the United States.²⁴

• In a population-based study of people with HIV or AIDS, identified as at increased risk for group "O" infection based on country of birth (n = 155), 2 cases of Group "O" infection and 27 cases of non-B, group M infection were identified. Both cases of Group "O" infections were identified in individuals born in Africa.²⁵

Western Europe:                 

• Rising prevalence of HIV-1 non-B subtypes has been reported in some Western European countries, and most of these infections could be attributed to countries where non-B HIV subtypes predominate. Many of these studies are reviewed by Thomson and Najera.²⁶

• Group "O" HIV, which is most commonly found West Africa, has been identified in Western Europe including countries such as Norway²⁷, Spain²⁸, and France.²⁹

• Recombinant strains of HIV-1 have also been detected in countries including the UK³⁰, Spain³¹, and Greece.³²

Comment

The introduction of variant HIV strains into Canada will invariably challenge existing diagnostic tests and interpretation algorithms. Depending on the impact that subtypes have on vaccine effectiveness and efficacy, it may direct the course of future vaccine research and testing. And, depending on future findings related to subtype-specific transmissibility, pathogenicity and treatment, it may play a role in changing the nature of the HIV epidemic in Canada. It is therefore important to implement the systematic collection and analysis of data related to strain surveillance across Canada.

References:

1. Simon F, Mauclere P, Roques P, et al. Identification of a new human immunodeficiency virus type distinct from group M and group O. Nature 1996; 4:1032-7.                  

2. Robertson DL,  Anderson JP,  Bradac JA, et al. HIV-1 nomenclature proposal. Science 2000. 288(5463):55-6.

3. Hu DJ, Buve A, Baggs J et al. What role does HIV-1 subtype play in transmission and pathogenesis? An epidemiological perspective AIDS 1999; 13:873-81.

4. Tatt ID, Barlow KL, Nicoll A et al. The public health significance of HIV-1 subtypes. AIDS 2001; 15(Suppl. 5):S59-S71.

5. Kuiken C, Thakallapalli R, Esklid A, et al. Genetic analysis reveals epidemiologic patterns in the spread of human immunodeficiency virus. Am J. Epidemiol 2000; 152(9):814-22.

6. Kanki PJ, Travers KU, Mboup S, et al.  Slower heterosexual spread of HIV-2 than HIV-1. Lancet 1994; 343:943-6.

7. Adjorlolo-Johnson G, De Cock KM, Ekpini et al.  Prospective comparison of mother-to-child transmission of HIV-1 and hIV-1 in Abidjan, Ivory Coast.  JAMA 1994; 272:462-6.

8. Mastro TD & de Vincenzi I. Probabilities of sexual HIV-1 transmission. AIDS 1996; 10 (suppl A):S75-82.

9. Shaffer N, Roongpisuthipong A, Siriwasin W, et al.  Maternal viral load and perinatal human immunodeficiency virus type 1 subtype E transmission, Thailand.  J Infect Dis 1999; 179:590-9.

10. Kunanusont C, Foy HM, Kreiss JK, et al. HIV-1 subtypes and male-to-female transmission in Thailand. Lancet 1995; 345(8957):1078-83.

11. Renjifo B, Fawzi W, Mwakagile D, et al.  Differences in perinatal transmission among human immunodeficiency virus type 1genotypes. J Hum Virol 2001; 4(1):16-25.

12. Hu DJ, Vanichseni S, Mastro TD, et al. Viral load differences in early infection with two HIV-1 subtypes. AIDS 2001; 15(6): 683-91. 

13. Pepin J, Morgan G, Dunn D et al.  HIV-2 induced immunosuppression among asymptomatic West African prostitutes: evidence that HIV-2 is phathogenic, but less so than HIV-1. AIDS 1991; 5:1165-72.

14. Whittle H, Morris J, Todd J et al.  HIV-2 infected patients survive longer than HIV-1 infected patients. AIDS 1994; 6:803-7.

15. Health Canada. HIV-1 strain and primary drug resistance in Canada. Surveillance report to June 30, 2002. Division of HIV/AIDS Epidemiology and Surveillance, Centre for Infectious Disease Prevention and Control, Health Canada, 2002. URL: (http://www.phac-aspc.gc.ca/publicat/aids-sida/haic-vsac0602/index.html).

16. Montpetit M.  HIV-1 subtype A in Canada. AIDS-Res-Hum-Retroviruses. 1995; 11(11):1421-2.   

17. Alexander C, Dong W, Chan K, et al. HIV-1 non-B subtypes in a large North American cohort: prevalence and response to antiretroviral therapy. Seventh Conference on Retroviruses and Opportunistic Infections. San Francisco, CA. Jan. 31-Feb 3, 2000;  #174.

18. Neumann PW,  Lepine D, Woodside M, et al. HIV-2 infection detected in Canada. Can Dis Wkly Rep 1988 Jul 16;14(28):125-6.

19. Montpetit ML, Ratnam S, Campbell C et al.  Molecular epidemiological analysis of Human Immunodeficiency Virys type 1 in Newfoundland, Canada. AIDS-Res-Hum-Retroviruses, 1998; 14(13):1205-9.

20. Bernier L, Lamothe F, Bruneau J, et al. Eighth Annual Canadian Conference on AIDS, Vancouver BC May 1-4 1999.  Can J Inf  Dis 1999; 10 (suppl B): 104A

21. Major C, for the POLARIS Seroconverter Study Group. Proceedings of the Division of HIV Epidemiology and Surveillance, Annual Meeting, BHST, CIDPC, Health Canada. Halifax, Nov. 16-18 2000.

22. Gao F, Yue L, Hill SC, et al.  HIV-1 sequence subtype D in the United States. AIDS Res Hum Retroviruses 1993; 10:625-7.

23. Zaidi I, Weinstock H, Kalish ML, et al. Surveillance for HIV-1 subtypes in the United States, 1998-present.  Seventh Conference on Retroviruses and Opportunistic Infections. San Francisco, CA. Jan 31-Feb 3, 2000; # 215.

24. Hanna GJ, Balaguera H, Steger K, et al. Eighth Conference on Retroviruses and Opportunistic Infections, Chicago, IL. Feb 5-8, 2001; #460.

25. Sullivan PS, Do AN, Ellenberger D, et al. Human immunodeficiency virus (HIV) subtype surveillance of African-born persons at risk for group O and group N HIV infections in the United States. J Infec Dis 2000; 181(2):461-9.

26. 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(12):1732-7.

27. Jonassen T, Stene-Johansen K, Berg ES, et al. Sequence analysis of HIV-1 group O from Norwegian patients infected in the 1960s. Virology 1997; 231:43-7.

28. Soriano V, Gutierrez M, Garcia-Lerma G, et al. First case of HIV-1 group O infection in Spain. Vox Sang 1996; 71(1):66

29. Couturier E, Damond F, Roques P. et al. HIV-1 diversity in France, 1996-1998. AIDS 2000 Feb 18; 14(3):289-96.

30. Barlow KL, Tatt ID, Cane  PA, et al. Recombinant strains of HIV type 1 in the United Kingdom. AIDS Res Hum   Retroviruses, 2001; 17(5):467-74.

31. Holguin A, Rodes B, & Soriano V. Recombinant human immunodeficiency viruses type 1 circulating in Spain. AIDS Res Hum Retroviruses 2000; 16(5):505-11.

32. Paraskevis D, Magiorkinis M, Vandamme AM, et al. Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated 'subtype I' reveals a unique complex A/G/H/K mosaic pattern.  J Gen Virol 2001; 82(Pt 3):575-80.

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