Both HIV-1 and HIV-2 likely entered the human population from their respective primates hosts sometime in the early part of the twentieth century [1–3], however, despite similar modes of transmission, HIV-1 has evolved into a much more successful human pathogen, spreading globally and to date killing more than 30 million individuals and currently infecting an additional approximately 34 million people . In contrast, HIV-2 has had limited global spread and remains mostly confined to West Africa, with an estimated 1–2 million infected [5–7]. The reasons and mechanisms for the disparate epidemiology and virulence of HIV-1 and HIV-2 are yet to be fully elucidated, however, numerous studies over the last three decades have demonstrated that compared with HIV-1, HIV-2 infection is characterized by a much longer asymptomatic stage, lower plasma viral loads, slower decline in CD4 cell count, lower mortality rate due to AIDS, lower rates of mother-to-child transmission, and lower rates of genital shedding and sexual transmission [8–17].
HIV-2 prevalence in West Africa appeared to peak in the 1970–1980s, with its epicenter in and around Guinea-Bissau [5,18–21]. For example, in a community-based prevalence study of HIV infection conducted in 1987, in 100 randomly selected ‘houses’ (1329 individuals), none were HIV-1 seropositive, and 4.7% were seropositive for HIV-2 (including 0.6% in children, 8.9% in those 15 years old or more, and 20% in those 40 years old or more) . The finding of higher HIV-2 prevalence in the older age distribution in multiple studies from the 1980s suggests that events prior to the recognition of AIDS in 1981 likely caused its rapid spread, and that these factors have since declined. How HIV-2, seemingly poorly adapted to human-to-human transmission, ever got to such high prevalence rates in parts of West Africa has been a matter of some debate and speculation. The multiple wars of independence, human displacement and migration into cities, increase of commercial sex work and unsterile traditional practices and parenteral injections from early medical treatment and vaccination campaigns have been suggested as potential causes [21–24]. What is clear, however, is over the last two decades, HIV-2 prevalence and incidence are slowly waning in West Africa, the reason for that are also not entirely clear [25–32].
The current study by de Silva et al.  in this issue of the journal provides new insight into this issue by comparing the population dynamics of HIV-2 and HIV-1 and by characterizing ongoing HIV-2 transmission in rural Guinea-Bissau. The authors are in a unique position to perform such a study using the well characterized ‘Caio Cohort’, a village-based community cohort in rural Guinea-Bissau that has been studied for approximately two decades. The authors use well validated phylogenetic and phylodynamic analyses, using Bayesian methods on both HIV-2 gag and env, as well as HIV-1 env sequences, from 103 HIV-2-infected and 56 HIV-1-infected patients. Bayesian skyline plots showed remarkably similar trajectories for HIV-2 and then HIV-1 (although offset by approximately 20 years), following initial introduction with an initial lag phase, a rapid rise and then plateau phase for the effective population sizes (Ne) of both viruses. One potential explanation the authors provide for this pattern is competitive exclusion of HIV-2 by HIV-1, as it was subsequently introduced into the community. Previous modeling work has suggested that approximately 30% of HIV-2 decline could be explained by competitive exclusion, with approximately 70% attributed to sociobehavioral changes . Data in changes in prevalence and incidence of HIV-2/HIV-1 dual infections during this transition period in might provide additional data for this hypothesis. Seroincident infections, compared with seroprevalent (pre-1989) were found more often in HIV-2 transmission clusters, with approximately 50% of all individuals contributing to ongoing transmission. This finding is not too surprising, given the rural community-based nature of the cohort with limited in and out migration. However, given the long time period between serosurveys in the cohort, ‘seroincident’ effects should be viewed with some caution. The finding that antiretroviral-naive HIV-2 phylogenetically linked sexual partners often had discordant viral loads (undetectable versus detectable) is a novel finding and may indicate that host factors predominately dictate viral load and the subsequent risk of disease progression in HIV-2 infection.
There has been recent excitement about possibility of ending the HIV-1 pandemic in the coming decades with current and forthcoming treatment and prevention strategies [35–37]. Recently, Bruhn and Gilbert  suggested that a more thorough understanding of the dynamics of the HIV-2 epidemic, its apparent slow rise in the first half of the twentieth century, exponential spread in parts of West Africa, plateau phase of relatively high prevalence in endemic areas, and slowly waning incidence and prevalence over the last two decades can serve as harbinger of what we might hope to expect with the HIV-1 pandemic if appropriate interventions and efforts are successful. Appropriate analysis and modeling of the factors contributing to the waning HIV-2 epidemic may provide crucial insight as how to target these same factors for HIV-1. Similarly, treatment as prevention strategies for HIV-1, that are premised on lowering ‘community viral load’ and thereby decreasing HIV-1 transmission [39,40], might be informed by further examination and modeling of how the naturally low and often undetectable viral loads, without antiretroviral therapy, in HIV-2 infection have contributed to the waning HIV-2 epidemic. The HIV-2 epidemic may provide a unique opportunity to teach us much about how to end the HIV-1 pandemic, but only if we have the intelligence and foresight to learn from it.
I would like to thank Papa Salif Sow and Robert A. Smith for helpful discussions.
Conflicts of interest
There are no conflicts of interest to declare.
Funding: No specific funding for this editorial.
1. Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, et al. Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes [see comments]
2. Korber B, Muldoon M, Theiler J, Gao F, Gupta R, Lapedes A, et al. Timing the ancestor of the HIV-1 pandemic strains
3. Lemey P, Pybus OG, Wang B, Saksena NK, Salemi M, Vandamme AM. Tracing the origin and history of the HIV-2 epidemic
. Proc Natl Acad Sci USA
5. De Cock KM, Adjorlolo G, Ekpini E, Sibailly T, Kouadio J, Maran M, et al.Epidemiology and transmission of HIV-2. Why there is no HIV-2 pandemic.JAMA
6. Gottlieb GS, Eholie SP, Nkengasong JN, Jallow S, Rowland-Jones S, Whittle HC, et al. A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa
2008; 22:2069–2072.discussion 2073–2064.
7. de Silva TI, Cotten M, Rowland-Jones SL. HIV-2: the forgotten AIDS virus
. Trends Microbiol
8. Kanki PJ, Travers KU, MBoup S, Hsieh CC, Marlink RG, Gueye-NDiaye A, et al. Slower heterosexual spread of HIV-2 than HIV-1
9. Simon F, Matheron S, Tamalet C, Loussert-Ajaka I, Bartczak S, Pepin JM, et al. Cellular and plasma viral load in patients infected with HIV-2
10. Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1
11. Comparison of vertical human immunodeficiency virus type 2 and human immunodeficiency virus type 1 transmission in the French prospective cohort. The HIV Infection in Newborns French Collaborative Study Group.Pediatr Infect Dis J
12. Adjorlolo-Johnson G, De-Cock KM, Ekpini E, Vetter KM, Sibailly T, Brattegaard K, et al.Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast.JAMA
13. Prazuck T, Yameogo JM, Heylinck B, Ouedraogo LT, Rochereau A, Guiard S-JB, et al. Mother-to-child transmission of human immunodeficiency virus type 1 and type 2 and dual infection: a cohort study in Banfora, Burkina Faso
. Pediatr Infect Dis J
14. Gottlieb GS, Sow PS, Hawes SE, Ndoye I, Redman M, Coll-Seck AM, et al. Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa
. J Infect Dis
15. Gilbert PB, McKeague IW, Eisen G, Mullins C, Gueye NA, Mboup S, et al. Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal
. Stat Med
16. Gottlieb GS, Hawes SE, Agne HD, Stern JE, Critchlow CW, Kiviat NB, et al. Lower levels of HIV RNA in semen in HIV-2 compared with HIV-1 infection: implications for differences in transmission
17. Hawes SE, Sow PS, Stern JE, Critchlow CW, Gottlieb GS, Kiviat NB. Lower levels of HIV-2 than HIV-1 in the female genital tract: correlates and longitudinal assessment of viral shedding
18. Poulsen AG, Kvinesdal B, Aaby P, Molbak K, Frederiksen K, Dias F, et al.Prevalence of and mortality from human immunodeficiency virus type 2 in Bissau, West Africa.Lancet
19. Poulsen AG, Aaby P, Gottschau A, Kvinesdal BB, Dias F, Molbak K, et al. HIV-2 infection in Bissau, West Africa, 1987–1989: incidence, prevalences, and routes of transmission
. J Acquir Immune Defic Syndr
20. Poulsen AG, Aaby P, Jensen H, Dias F. Risk factors for HIV-2 seropositivity among older people in Guinea-Bissau. A search for the early history of HIV-2 infection
. Scand J Infect Dis
21. Pepin J, Plamondon M, Alves AC, Beaudet M, Labbe AC. Parenteral transmission during excision and treatment of tuberculosis and trypanosomiasis may be responsible for the HIV-2 epidemic in Guinea-Bissau
22. Mansson F, Biague A, da Silva ZJ, Dias F, Nilsson LA, Andersson S, et al. Prevalence and incidence of HIV-1 and HIV-2 before, during and after a civil war in an occupational cohort in Guinea-Bissau, West Africa
23. Mansson F, Alves A, Silva ZJ, Dias F, Andersson S, Biberfeld G, et al. Trends of HIV-1 and HIV-2 prevalence among pregnant women in Guinea-Bissau, West Africa: possible effect of the civil war 1998 1999
. Sex Transm Infect
24. Pepin J. The origin of AIDS
. New York:Cambridge University Press; 2011.
25. Larsen O, da Silva Z, Sandstrom A, Andersen PK, Andersson S, Poulsen AG, et al. Declining HIV-2 prevalence and incidence among men in a community study from Guinea-Bissau
26. Schim van der Loeff MF, Awasana AA, Sarge-Njie R, van der SM, Jaye A, Sabally S, et al.Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2.Int J Epidemiol
27. Eholie S, Anglaret X. Commentary: decline of HIV-2 prevalence in West Africa: good news or bad news?
. Int J Epidemiol
28. Hamel DJ, Sankale JL, Eisen G, Meloni ST, Mullins C, Gueye-Ndiaye A, et al. Twenty years of prospective molecular epidemiology in Senegal: changes in HIV diversity
. AIDS Res Hum Retroviruses
29. da Silva ZJ, Oliveira I, Andersen A, Dias F, Rodrigues A, Holmgren B, et al. Changes in prevalence and incidence of HIV-1, HIV-2 and dual infections in urban areas of Bissau, Guinea-Bissau: is HIV-2 disappearing?
30. Tienen C, van der Loeff MS, Zaman SM, Vincent T, Sarge-Njie R, Peterson I, et al. Two distinct epidemics: the rise of HIV-1 and decline of HIV-2 infection between 1990 and 2007 in rural Guinea-Bissau
. J Acquir Immune Defic Syndr
31. Gianelli E, Riva A, Rankin Bravo FA, Da Silva Te D, Mariani E, Casazza G, et al. Prevalence and risk determinants of HIV-1 and HIV-2 infections in pregnant women in Bissau
. J Infect
32. Heitzinger K, Sow P, Dia Badiane N, Gottlieb G, N’Doye I, Toure M, et al
. Trends of HIV-1, HIV-2, and dual infection in women attending outpatient clinics in Senegal, 1990–2009.Int J STD AIDS
33. de Silva T, Van Tienen C, Onyango C, Jabang A, Vincent T, Schim Van Der Loeff MF, et al.Population dynamics of HIV-2 in rural West Africa: comparison with HIV-1 and ongoing transmission at the heart of the epidemic.AIDS
34. Schmidt WP, Van Der Loeff MS, Aaby P, Whittle H, Bakker R, Buckner M, et al. Behaviour change and competitive exclusion can explain the diverging HIV-1 and HIV-2 prevalence trends in Guinea-Bissau
. Epidemiol Infect
35. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model
36. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy
. N Engl J Med
38. Bruhn CA, Gilbert MT. HIV-2 down, HIV-1 to go? Understanding the possibilities of treatment as prevention
. Lancet Infect Dis
39. Das M, Chu PL, Santos GM, Scheer S, Vittinghoff E, McFarland W, et al. Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco
. PLoS One
40. Castel AD, Befus M, Willis S, Griffin A, West T, Hader S, et al. Use of the community viral load as a population-based biomarker of HIV burden