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"Test and Treat": Is It Enough?
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Clin Infect Dis. (March 15 2011) 52 (6): 801-802.
Joep M. A. Lange
Center for Poverty-Related Communicable Diseases, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health & Development, Amsterdam, the Netherlands
Correspondence: Joep M.A. Lange, PhD, PharmAccess International, University of Amsterdam, Amsterdam, the Netherlands (j.lange@amc.uva.nl).
(See the article by Gardner et al, on pages 793-800.)
Over the past few years, the distinction between human immunodeficiency virus (HIV) prevention and HIV treatment has become blurred. At the basis of this lies mounting evidence that effective antiretroviral therapy, which reduces plasma HIV-1 to minimal levels, also reduces sexual transmissibility of HIV to virtually nil [1, 2]. Scaling up of antiretroviral therapy has thus been proposed as a strategy to lower the number of new HIV infections at the population level [3]. A strategy of universal voluntary HIV testing for persons aged ≥15 years and immediate administration of antiretroviral therapy for those found to be positive, in a mathematical model based on data from South Africa, could lead to rapid reductions of HIV prevalence, reducing the prevalence to <1% within 50 years [4]. Although this model has been criticized as being overly simplistic and optimistic [5], and although it may depend on context [6] it has generated an enormous interest in "test and treat" strategies as a valuable addition to the HIV prevention armamentarium. It converges with a trend toward earlier antiretroviral treatment initiation in guidelines for both the developed [7] and developing world [8]. Early initiation of antiretroviral therapy increases survival for those infected [9, 10], greatly reduces the incidence of tuberculosis [11], and is also likely to reduce HIV incidence.
However, this will only happen with sufficient engagement in HIV care by those infected. The paper by Gardner et al in this issue of Clinical Infectious Diseases reviews the spectrum of engagement in care for HIV-infected individuals in the United States. Gardner and colleagues' most shocking finding is that-some 15 years after the introduction of highly effective antiretroviral therapy (HAART) and 4 years after the introduction of a well-tolerated, highly effective, single-pill, fixed-dose combination treatment for first-line therapy-of >1.1 million HIV-infected persons in the United States, only an estimated 19% have an undetectable plasma HIV-1 RNA level. It is thus not surprising that, over this period, HIV incidence has not declined in the United States. Determinants of the low number of people with plasma viral loads that are less than the detection limit of standard assays are lack of knowledge about HIV status, failure to initiate HIV care after diagnosis, failure to remain in care, failure to initiate antiretroviral therapy, discontinuation of therapy, and antiretroviral drug resistance. The authors acknowledge that the model they present may be simplistic, but that they are unaware of data from cohorts of individuals tracked over the engagement in care continuum that can more precisely determine the true proportion of HIV-infected individuals in the United States with an undetectable plasma HIV level. It is, however, unlikely that more robust data would grossly alter the picture. In the Netherlands, of 16,832 patients with a registered date of HIV diagnosis, 83% have ever received HAART; however, even in recent years, 56% presented late for care (ie, with a CD4+ cell count ²350 cells/mm3). In those who received a diagnosis of HIV infection during the period 1996-2010 with a CD4+ lymphocyte count ≥350 cells/mm3, 13% initiated HAART when their CD4+ cell count was <200 cells/mm3. Of 13,035 patients currently in follow-up, 77% have a plasma viral load <500 copies/mL. An estimated 8000-10,000 HIV-infected persons in the Netherlands who do not know their serostatus, which represents 38%-43% of the HIV-infected population; this adds up to 52%-56% of the HIV-infected population not having an undetectable plasma HIV RNA level [12]. This is a better figure than the US estimate, but for a country with universal health insurance coverage and fewer income disparities than in the United States, it is certainly not good enough. Moreover, the Netherlands has witnessed a resurgent HIV epidemic among men who have sex with men since the introduction of HAART in 1996, with an increase of the risk behavior rate of 66% [13]. It is estimated that, in low- and middle-income countries, which have experienced a massive scale-up of antiretroviral therapy over the past few years, ~76% of patients who have started HAART are retained in care during the first year of follow-up [14]-another alarming figure.
Where does all of this lead us? In their paper, Gardener and colleauges simulated the impact of successful interventions to improve specific components of engagement in care on the proportion of individuals with undetectable plasma HIV levels in the United States. In this simulation, improvement in any single component of engagement in care has minimal impact. In an idealistic scenario, in which all components are successfully tackled in 90% of individuals, ~34% of HIV-infected individuals will remain viremic and able to transmit HIV to others. Bendavid et al [15] showed similar encouraging-but, at the sime time, sobering-figures in a simulation of the effect of "test and treat" on HIV-related mortality and new HIV infections in South Africa. In addition, it needs to be realized that it will be difficult to target people with primary HIV infection, who may be responsible for a significant number of cases of further HIV transmissions [16-18]. Thus, while putting and keeping more HIV-infected people on treatment may lower HIV transmission rates at the population level, it is unlikely that "test and treat" strategies by themselves, even if vigorously and comprehensively pursued, will be sufficient to end the HIV epidemic. It should be clear that "combination HIV prevention" [19], using a mix of available prevention tools, including "test and treat" strategies, in a context-specific manner based on knowledge about local, national, and regional epidemics, is the way forward.
The good news is that, recently, 2 proof of concept studies of HIV-negative subjects on the prophylactic efficacy of topical (1% tenofovir gel, applied in the vagina) or systemic (tenofovir-emtricitabine given orally) use of antiretrovirals have had positive outcomes [20, 21]. Vaginal microbicides and oral preexposure prophylaxis will be valuable further additions to the HIV prevention armamentarium and increase our chances to turn the tide of the HIV epidemic decisively.
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