In this issue of the Journal, Beer et al. present the results of their firm study of differences in blood plasma HIV RNA viral load between HIV-infected Black and White MSM in the US, as a proxy for HIV infectiousness possibly explaining (part of) the racial disparity in HIV incidence between these two groups. On the basis of one of the most thorough and detailed analyses of factors driving racial health disparities in the Western world to date, Millet et al.[2–4] hypothesized assortative sexual mixing, higher background prevalence and incidence of sexually transmitted infections (STIs), and lower access, uptake and adherence to antiretroviral therapy (ART) among (HIV-infected) Black MSM as possible explanations for the higher HIV incidence within this subpopulation.
Beer et al. analyzed data from a subpopulation of sexually active Black (n = 314) and White MSM (n = 696) out of 4217 persons (response rate 39%) who consented to interviews and medical file review, from a total sample of 9338 adults attending HIV care facilities throughout the US (The Medical Monitoring Project) . After a process of weighting and adjustment, these 4217 individuals were reported to be representative for the 421 186 HIV-infected adults receiving HIV care in the US between January and May 2009 .
From their analyses, it appeared that whereas Black and White MSM did not differ in sexual behavior, Black MSM were less likely to be on ART (effect size 11%), and if on ART, they were less likely to be virally suppressed (effect size 21%). After adjustment for confounders in multivariable analysis, the difference in ART uptake persisted (effect size 7%), but the difference in viral suppression disappeared.
Whereas the differences in ART uptake and HIV viral suppression between Black and White MSM are in the expected direction, the magnitude of the dissimilarities seems to be too minimal to account for a substantial part of the six-fold difference in the rate of new HIV infections between them. This raises the question of what might then be driving these substantial disparities in HIV incidence rates between Black and White MSM. Thus, additional causes, such as sexual mixing patterns and their ramifications for the pool of circulating HIV-infecting viruses, and the role of prevalent and incident STIs as HIV transmission facilitating co-factors among Black and White MSM [2–4], need to be evaluated more in detail to see if they can help unravel the reasons behind the huge difference in HIV incidence. For example, increased intra-racial mixing among Black MSM may be associated with recycling of phenotypic representations of HIV with a successful history of previous transmissions, such as those found clustering or in chains of transmission associated with acute and early HIV infection [5–8]. Disregarding the absence of vast differences in ART uptake and HIV viral expression between Black and White MSM, the choice of blood plasma HIV viral load as a proxy for HIV infectiousness in MSM is less than perfect. This proxy assumption relies for a large part on the results of the HIV Prevention Trials Network 052 study , conducted among HIV serodiscordant couples. However, only 3% of couples in that study were nonheterosexual, too few to extend its internal validity to the male homosexual population. In addition, the question of whether it is possible to equate the penile–vaginal heterosexual environment from couples recruited from four different continents with the highly inflammatory challenged and possibly damaged penile rectal environment among MSM in the US deserves a lot more caution than it has received to date. Moreover, in a recent study in 114 MSM with suppressed blood plasma HIV RNA (also from the US), 10% had detectable HIV RNA and 63% had evidence of at least one type of herpes virus in seminal fluid . It should also be mentioned that a trend for an association was observed between cytomegalovirus (CMV) expression, Epstein–Barr virus presence and HIV RNA in seminal fluid, whereas CMV was found predictive of seminal HIV RNA . In addition, it is important to note that mounting phylogenetic and molecular epidemiologic evidence suggests that in rising or ongoing HIV epidemics among MSM, acute HIV infection (AHI) may account for up to 50% or more of new HIV infections [5–8]. And this proportion may further increase in the presence of biological or behavioral co-factors in the index case or host, such as STIs or penile–rectal trauma associated with high-intensity sexual contact with multiple different consecutive sexual partners associated with the use of stimulant and erectile dysfunction agents [11,12]. In this scenario, most new HIV infections will have already occurred before ART for prevention is initiated. Alternatively, early ART can make a substantial difference by interrupting the AHI transmission chain, if it is initiated early enough. Recently, a study among 90 MSM with AHI in Bangkok, Thailand, demonstrated that immediate administration of ART following AHI detection was associated with an instant sharp drop in HIV RNA viral load in blood plasma, seminal fluid and ano-rectal lavage specimens, with 73% of patients having undetectable HIV RNA in seminal plasma at week 4 and close to 100% having undetectable viral load in all compartments by week 12 . By contrast, seminal HIV viral load levels have been shown to peak at 30 days after HIV acquisition in untreated individuals . In addition, HIV transmission risk behavior (unprotected anal intercourse) fell by 70–85% (dependent on partner type) upon learning about AHI, reductions sustained through 48 weeks of follow-up . Furthermore, in these early treated men, HIV disease prognosis improved considerably, with 90% having undetectable cell-integrated HIV RNA in peripheral blood mononuclear cells, commensurate with ‘Elite Controllers’ of HIV infection [15,16]. However, even if such an early combined equipoised curative and preventive intervention could be successfully replicated among MSM in the US, the difference between Black and White MSM may not disappear. These and other types of racial health disparities will only be reduced or eliminated if the structural barriers in timely access to high-quality healthcare for Black people in general and for Black MSM in particular are resolved [2–4].
Conflicts of interest
There are no conflicts of interest.
1. Beer L, Oster AM, Mattson CL, Skarbinski J. for the Medical Monitoring ProjectDisparities in HIV transmission risk among HIV-infected black and white men who have sex with men United States, 2009
2. Millett GA, Peterson JL, Wolitski RJ, Stall R. Greater Risk for HIV infection of black men who have sex with men: a critical literature review
. Am J Public Health
3. Millett GA, Peterson JL, Flores SA, Hart TA, Jeffries WL, Wilson PA, et al. Comparisons of disparities and risks of HIV infection in black and other men who have sex with men in Canada, UK, and USA: a meta-analysis
4. Millett GA, Flores SA, Peterson JL, Bakeman R. Explaining disparities in HIV infection among black and white men who have sex with men: a meta-analysis of HIV risk behaviors
5. Brenner BG, Roger M, Routy JP, Moisi D, Ntemgwa M, Matte C, et al. High rates of forward transmission events after acute/early HIV-1 infection
. J Infect Dis
6. Fisher M, Paoa D, Brown AE, Sudarshia D, Gill ON, Cane P, et al. Determinants of HIV-1 transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach
7. Ambrosioni J, Junier T, Delhumeau C, Calmy A, Hirschel B, Zdobnov E, et al. Impact of HAART on the molecular epidemiology of newly diagnosed HIV infections in Geneva
8. Audelin AM, Cowan SA, Obel N, Nielsen C, Jørgensen LB, Gerstoft J. Phylogenetics of the Danish HIV epidemic: the role of very late presenters in sustaining the epidemic
. J Acquir Immune Defic Syndr
9. 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
10. Gianelli S, Smith DM, Vargas MV, Little SJ, Richman DD, Daar ES, et al. Shedding of HIV and human herpesviruses in the semen of effectively treated HIV-1 infected men who have sex with men
. Clin Infect Dis
11. van Griensven F, Phanuphak N, Kroon E, Fletcher J, Pinyakorn S, Chomchey N, et al.Acute HIV infection detection and control reduces HIV infectiousness and transmission risk behavior among men who have sex with men in Bangkok, Thailand
. 7th IAS Conference on HIV Pathogenesi, Treatment and Prevention, Kuala Lumpur, Malaysia, 2013 [Abstract WELBC03].
12. Fisher DG, Reynolds GL, Ware MR, Napper LE. Methamphetamine and Viagra use: relationship to sexual risk behaviors
. Arch Sexual Behav
13. Mayer K. Sexually transmitted diseases in men who have sex with men
. Clin Infect Dis
2011; 53 (S3):S79–S83.
14. Pilcher CD, Joaki G, Hoffman IF, Martinson FE, Mapanje C, Stewart PW, et al. Amplified transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection
15. Ananworanich J, Schuetz A, Vandergeeten C, Sereti I, de Souza M, Rerknimitr R, et al. Impact of multitargeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection
. PLOS One
16. Ananworanich J, Vandergeeten C, Chomchey N, Phanuphak N, Ngauy V, Sekaly RP, et al.Early ART intervention restricts the seeding of the HIV reservoir in long lived central memory CD4 T cells
. 20th Conference on Retroviruses and Opportunistic Infections, Atlanta GA 2013 [Abstract 47].