Plus ça change ... antiretroviral therapy, HIV prevention, and the HIV treatment cascade.

Global commitments by 2015 include the Millennium Development Goals, elimination of pediatric human immunodeficiency virus (HIV) infection, and having 15 million persons on antiretroviral therapy (ART); in this context, the major question facing the global AIDS response is how best to use ART for individual health as well as the public health. Recognition of the HIV prevention benefit of ART has stimulated calls for earlier and more widespread ART globally, with the 96% efficacy in reducing sexual transmission demonstrated in the landmark HIV Prevention Trials Network (HPTN) 052 [1] study often quoted. Earlier in 2013, the World Health Organization (WHO) issued consolidated ART guidelines that recommend initiation of ART at a CD4 count of ≤500 cells/μL [2], and many expect global guidelines to eventually recommend ART for all persons living with HIV, irrespective of the absence of data from randomized clinical trials [3]. There is more to HIV treatment than guidelines, however, and in the current issue of Clinical Infectious Diseases, McNairy and El-Sadr [4] usefully discuss the health-systems challenges inherent to the “HIV treatment cascade.” This term refers to the sequential steps that take individuals from HIV diagnosis through enrollment into care, timely initiation of ART, adherence to treatment, and viral suppression. An intact cascade is essential if the benefits of ART are not to be squandered and more HIV-infected persons are to be safely placed on therapy. The HIV treatment cascade is not a new concept but uses earlier modeling applied to tuberculosis and sexually transmitted infections, referred to, respectively, as the Piot and Piot-Fransen models [5, 6]. For these conditions, the multiple steps required for medical success are at risk from constant leakage. Dropout can occur at numerous points so that the final number of beneficial outcomes may be small compared to the number of people entering the cascade. Such observations apply to medical care more broadly and explain the relatively poor impact from interventions for many chronic diseases such as hypertension when analyzed at the population level. In comparison, once-only interventions with sustained benefit such as male circumcision for HIV prevention can have greater population-level impact despite imperfect efficacy. The central role that ART plays in today’s HIV prevention response has roots early in the pandemic. Analytic epidemiologic studies showed that viral load was associated with risk of transmission for all transmission modes. Zidovudine monotherapy reduced transmission from the infected partner in discordant couples in the late 1980s [7], as well as from mothers to infants in the landmark AIDS Clinical Trials Group (ACTG) 076 study [8]. Public health officials raised the possibility of ART and viral load suppression playing a role in reducing HIV transmission at a population level more than a decade ago [9]. The enormous interest today in HIV treatment as prevention and the impetus to implement it result from different but allied forces: the early observations cited above; mathematical modeling showing that ART implemented on a wide scale could substantially reduce and potentially control generalized HIV epidemics [10]; programmatic experience confirming reduced HIV transmission at a population level with ART scale-up [11, 12]; the results of the HPTN 052 study [1]; and the general belief that earlier treatment would be beneficial for individual health. The single most important indicator that HIV treatment and public health programs should be concerned about today is viral load, which is key to both transmission and disease progression. Monitoring and evaluation efforts strive to capture indicators that describe how well viral load is being suppressed across the population, either through depictions of the cascade or summary estimates such as community Received and accepted 7 January 2014. Correspondence: Kevin M. De Cock, MD, Centers for Disease Control and Prevention Kenya, Unit 8900, Box 360, DPO AE 09831-0360 (kdecock@ke.cdc.gov). Clinical Infectious Diseases Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. Thiswork iswritten by (a) US Government employee(s) and is in the public domain in the US. DOI: 10.1093/cid/ciu026