HIV/AIDS Epi Update - May 2004

HIV-1 Strain Surveillance in Canada

Introduction

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 strain B continues to predominate, strains A, C, D, E, G and various circulating recombinants have been identified in Canada.

The overall prevalence of non- B
HIV-1 strains in Canada is 7.5%.

Among HIV-1 strains treatment-naïve individuals with newly diagnosed infection in Canada, there significantly higher proportions of non-B HIV-1 infections among females (compared males), among persons reporting heterosexual contact as primary exposure factor, among persons of Black, or mixed ethnicities.

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, and these lineages are called strains or subtypes. These include subtype designations A to E (subtype E is also referred to as 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 worldwide. In Canada, the USA and Western Europe, HIV-1 subtype B predominates. However, because of 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 USA 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 and Health Canada, laboratory samples (serum from individuals with newly diagnosed HIV) and corresponding epidemiological data are sent from the provincial health laboratories to Health Canada for HIV strain and drug resistance testing. The results are then shared with provincial and other stakeholders. 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 to 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 subtype affect sexual and maternal transmission rates.6-9 Some studies note differences in the biological properties of HIV-1 subtypes,10-12 but 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, evidence suggests that the immunologic responses may be less suppressed by HIV-2 than by HIV-1;^13,14 this needs to be clarified. 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 7.5% of the sampled population (n = 1,673) were infected with non-B subtypes (see Table 1 for subtype distribution).
• Preliminary results from the CHSDRSP suggest that a significant proportion of individuals infected with a non-B HIV-1 subtype are female, of 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 4.4% of HIV infections among individuals starting therapy.17 HIV-1 subtypes A, C, D and CRF01_AE were also 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 analyzed from infected injection drug users (n = 17) and men who have sex with men (n = 5) residing in Montreal were of subtype B.²⁰
• As of October 2003, 106 sequenced viruses of 107 participants in the Polaris HIV Seroconversion Study were found to be of subtype B. The one exception was a single subtype A/G recombinant.²¹

United States

• As early as 1993, subtype D was reported in the United States.²²
• Results from ongoing sentinel surveillance of strain and drug resistance by the Centers for Disease Control and Prevention have shown that 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, 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 of group O infection on the basis of country of birth (n = 155), two cases of group O infection and 27 cases of non-B, group M infection were identified. Both cases of group O infection were identified in individuals born in Africa.²⁵
• A study of HIV-infected blood donors during 1997-2000 found 2.1% of non-B subtypes.²⁶
• An investigation of a recently infected U.S. military cohort found a 5.4% prevalence of non-B subtypes, and these subtypes were associated with heterosexual activity (compared with homosexual/bisexual activity) and with overseas work.²⁷

Western Europe

• A 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. For example, a study of primary HIV infections in France in 1999-2000 found that 19% of subtypes were non-B.²⁸ A review of similar studies has been done by Thomson and Najera.²⁹
• Group O HIV, which is most commonly found in West Africa, has been identified in Western Europe, including countries such as Norway,³⁰ Spain³¹ and France.³²
• Recombinant strains of HIV-1 have also been detected, in countries such as the UK,33 Spain³⁴ and Greece.³⁵

Comment

The introduction of variant HIV strains into Canada will invariably challenge existing diagnostic tests and interpretation algorithms. Depending on the impact that strains have on vaccine effectiveness and efficacy, it may direct the course of future vaccine research and testing. Furthermore, depending on future findings related to strain-specific transmissibility, pathogenicity and treatment, HIV strain variation 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.

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