HIV-2, first suspected by serological findings in west African residents, was isolated from patients with AIDS originating from Cape Verde and Guinea Bissau [1,2]. Although HIV-2 causes AIDS, it is clearly less pathogenic than HIV-1 [3,4]. The viral load is significantly lower in HIV-2-infected patients, and consequently HIV-2 is less transmissible [5,6]. The precise diagnosis of HIV-2 has implications, particularly for monitoring RNA levels, as no specifically dedicated commercial assays are currently available, and for the choice of antiretroviral treatment, because HIV-2 strains are naturally resistant to non-nucleoside reverse transcriptase inhibitors and fusion inhibitors, and are less sensitive in vitro to some protease inhibitors [7,8]. HIV-2 is endemic in west Africa. Most cases described outside Africa have been traced to contacts with individuals from this endemic region. This has been particularly observed in European countries with historical links with west Africa such as France, the United Kingdom and Portugal [9–11]. No extensive epidemiological surveys have, however, allowed the determination of the exact prevalence of HIV-2 in these European countries. Similarly, HIV-1 group O variants are restricted geographically, mainly to Cameroon and the surrounding areas . Rare cases have been reported in industrialized countries, but the exact prevalence of these variants among HIV-1-infected patients is unknown. Similar to HIV-2, most of the commercially available assays for the quantification of HIV-1 RNA do not detect viral sequences from HIV-1 group O variants , and non-nucleoside reverse transcriptase inhibitors are inefficient at controlling HIV-1 group O replication .
Mandatory anonymous HIV case reporting was implemented in France in 2003, with which virological monitoring using dried serum spots was associated. The procedures and the first results of this surveillance system have been described elsewhere . In brief, any HIV-positive serology confirmed for the first time by a clinical laboratory must be reported, with a unique anonymous code for each patient. Clinical and epidemiological details are supplied by the physicians in charge of the patients. For each case, the laboratory is asked to send dried serum spots collected on filter papers from the serum sample obtained for the original diagnosis to the National Reference Centre (NRC). Although HIV notification is mandatory, virological surveillance is based on volunteer participation by both microbiologists and patients. The patient's consent for virological surveillance is obtained by the reporting clinician through the HIV notification form. Serological identification of the type and group of HIV is performed by enzyme-linked immunosorbent assay at the NRC, as described . Results from the NRC are then linked to the epidemiological data in the HIV national database using the patient's anonymous code. Any specific diagnosis of infection by either HIV-2 or HIV-1 group O implies transmission of the information to the clinical laboratory of origin in order to adapt the clinical, biological and therapeutic management of the patient.
Here we report the results of the HIV-2 and HIV-1 group O infections that were identified among new HIV diagnoses during the past 3 years. Between January 2003 and June 2006, 10 184 new diagnoses with participation in the virological surveillance were reported. Among these, 186 were from patients infected by HIV-2 [1.8%; 95% confidence interval (CI) 1.6–2.1], of which 164 (1.6%; 95% CI 1.4–1.9) were HIV-2 only and 22 (0.2%; 95% CI 0.1–0.3) were probable dual infections. The serological diagnosis of dual infection was based on similar high antibody binding to both the immunodominant epitope of gp41 and the V3 region of both HIV-1 and HIV-2 [16,17]. Such a stringent criteria was validated earlier , and more recently on a panel of samples for which single or dual infections were diagnosed by type-specific polymerase chain reaction (data not shown). Patients infected with HIV-2 were mostly citizens of a west African country (65%; n = 121), mainly Côte d'Ivoire (n = 64), Mali (n = 19) and Senegal (n = 12), but there were also 22 European individuals, 20 from France and two from Portugal (Fig. 1). The majority of cases was observed in women (63%; n = 118). Although the risk factor was unknown for 26% (n = 48) of cases, 72% (n = 134) of HIV-2 infections were caused by heterosexual transmission. HIV-2 was, however, identified in three men who have sex with men (MSM), one from France and two from the Americas.
Twelve patients (0.1%; 95% CI 0.1–0.2) were infected with HIV-1 group O variants. Most of them originated from the sub-Saharan endemic area: nine from Cameroon and one from Chad (Fig. 1). Two of those patients had dual M/O infection; those two cases have been described in detail earlier . The two other cases were French citizens who had probably been infected through heterosexual intercourse.
A specific serological diagnosis of HIV-2 infection may be missed if adapted confirmation tools are not routinely used in clinical laboratories, a situation that is frequent in non-endemic areas. There is a frequent use of HIV-1 Western blots for confirmatory diagnosis, on which serum samples positive for antibodies to HIV-2 may cross-react, even on envelope glycoproteins, leading to a misclassification as anti-HIV-1 positives . Similarly, HIV-1 group O infections are not systematically diagnosed as such, except if there are dissociations between clinical and biological findings in an HIV-1-positive patient; for example, AIDS stage with undetectable viral load. This is because there is no commercially available specific serological tool for this purpose. Therefore, there are no data that would provide estimates of the prevalence of these rare variants in western countries. The French national surveillance of new HIV diagnoses included the collection of dried serum spots to identify HIV serotypes with dedicated peptide immunoassays [16,17]. This allowed, for the first time, the provision of reliable estimates of the proportion of these rare variants in a European country. The results indicate that most of the cases diagnosed during this 3-year period still occurred in patients originating from the endemic areas, west Africa and Cameroon, for HIV-2 and HIV-1 group O, respectively. Three cases of HIV-2 infections were, however, reported in MSM, an observation that should deserve further attention because of the persistent high-risk behaviours in some individuals in the gay community.
Sponsorship: The National Reference Centre is funded by a grant from the Institut de Veille Sanitaire. The Institut de Veille Sanitaire is funded by the French Minister of Health. The enzyme-linked immunosorbent assays for serological discrimination between HIV variants were developed and validated through projects supported by the Agence Nationale de Recherche sur le Sida (ANRS, Paris, France). We thank all participants in the national surveillance programme, particularly the biologists, physicians and public health doctors.
1. Barin F, M'Boup S, Denis F, Kanki P, Allan JS, Lee TH, et al
. Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of West Africa. Lancet 1985; 2:1387–1389.
2. Clavel F, Guetard D, Brun-Vézinet F, Chamaret S, Rey MA, Santos-Ferreira O, et al
. Isolation of a new human retrovirus from West African patients with AIDS. Science 1986; 233:343–346.
3. Marlink R, Kanki PJ, Thior I, Travers K, Eisen G, Siby T, et al
. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science 1994; 265:1587–1590.
4. Matheron S, Pueyo S, Damond F, Simon F, Leprêtre A, Campa P, et al
. Factors associated with clinical progression in HIV-2 infected-patients: the French ANRS cohort. AIDS 2003; 17:2593–2601.
5. Berry N, Ariyoshi K, Jaffar S, Sabally S, Corrah T, Tedder R, et al
. Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection. J Hum Virol 1998; 1:457–468.
6. Kanki PJ, Travers K, M'Boup S, Hsieh CC, Marlink RG, Gueye-N'Diaye A, et al
. Slower heterosexual spread of HIV-2 than HIV-1. Lancet 1994; 343:943–946.
7. Reeves JD, Doms RW. Human immunodeficiency virus type 2. J Gen Virol 2002; 83:1253–1265.
8. Damond F, Brun-Vézinet F, Matheron S, Peytavin G, Campa P, Pueyo S, et al
. Polymorphism of the human immunodeficiency virus type 2 (HIV-2) protease gene and selection of resistance mutations in HIV-2-infected patients treated with protease inhibitors. J Clin Microbiol 2005; 43:484–487.
9. Matheron S, Mendoza-Sassi G, Simon F, Olivares R, Coulaud JP, Brun-Vezinet F. HIV-1 and HIV-2 AIDS in African patients living in Paris. AIDS 1997; 11:934–936.
10. Dougan S, Patel B, Tosswill JH, Sinka K. Diagnoses of HIV-1 and HIV-2 in England, Wales, and Northrn Ireland associated with west Africa. Sex Transm Infect 2005; 81:338–341.
11. Soriano V, Gomes P, Heneine W, Holguin A, Doruana M, Antunes R, et al
. Human immunodeficiency virus type 2 (HIV-2) in Portugal: clinical spectrum, circulating subtypes, virus isolation, and plasma viral load. J Med Virol 2000; 61:111–116.
12. Roques P, Robertson DL, Souquiere S, Damond F, Ayouba A, Farfara I, et al
. Phylogenetic analysis of 49 newly derived HIV-1 group O strains: high viral diversity but no group M-like subtype structure. Virology 2002; 302:259–273.
13. Gueudin M, Plantier JC, Lemée V, Schmitt MP, Chartier L, Bourlet T, et al
. Evaluation of the Roche Cobas TaqMan and Abbott real time extraction-quantification systems for HIV-1 subtypes. J Acquir Immune Defic Syndr 2007; 44:500–505.
14. Descamps D, Collin G, Letourneur F, Apetrei C, Damond F, Loussert-Ajaka I, et al
. Susceptibility of human immunodeficiency virus type 1 group O isolates to antiretroviral agents: in vitro phenotypic and genotypic analyses. J Virol 1997; 71:8893–8898.
15. Semaille C, Barin F, Cazein F, Pillonel J, Lot F, Brand D, et al
. Monitoring the dynamics of the HIV epidemic using assays for recent infection and serotyping among new HIV diagnoses: experience after 2 years in France. J Infect Dis 2007; 196:377–383.
16. Barin F, Plantier JC, Brand D, Brunet S, Moreau A, Liandier B, et al
. Human immunodeficiency virus serotyping on dried serum spots as a screening tool for the surveillance of the AIDS epidemic. J Med Virol 2006; 78(Suppl 1):S13–S18.
17. Baillou A, Janvier B, Leonard G, Denis F, Goudeau A, Barin F. Fine serotyping of human immunodeficiency virus serotype 1 (HIV-1) and HIV-2 infections by using synthetic oligopeptides representing an immunodominant domain of HIV-1 and HIV-2/simian immunodeficiency virus. J Clin Microbiol 1991; 29:1387–1391.
18. Brand D, Beby-Defaux A, Macé M, Brunet S, Moreau A, Godet C, et al
. First identification of HIV-1 groups M and O dual infections in Europe. AIDS 2004; 18:2425–2428.
19. Damond F, Apetrei C, Robertson DL, Souquière S, Lepretre A, Matheron S, et al
. Variability of human immunodeficiency virus type 2 infecting patients living in France. Virology 2001; 280:19–30.