Undoubtedly, future insights will occur on the front lines of the epidemic, through iterative trials that build upon and think beyond RV144. which full vaccine-induced protection from acquisition is not achieved, in which case durable control of established contamination will be required. Although there is usually reason to be optimistic that an effective HIV vaccine is possible, one of the major constraints moving forward will likely be constraints on funding to support a diversity of concepts at a time that this correlates of protection from acquisition and disease progression are still unknown. Given the scope of the epidemic and the economic climate, we must strive to do much more with less and seek to access additional resources, both scientific and monetary, from every possible source. strong class=”kwd-title” Keywords: Vaccine, Antiretrovirals, Economy Thirty years into the AIDS epidemic, reflection on medical accomplishments discloses stark PF 431396 contrasts. When HIV was conclusively identified as the causative agent,1,2 it was publicly anticipated that a vaccine would be available to prevent contamination within a few years. At that time, few antiviral brokers existed, and PF 431396 a pharmacologic treatment for the epidemic was not even entertained. Now it is male circumcision and antiretroviral therapy that have shown the greatest promise for preventing infections,3,4 and an effective vaccine continues to be elusive, to the point that some believe it will not be possible. Some question whether it will be necessary at all. With drug therapy, we have been able to progress to a stage of relative epidemic control in certain parts of the world although there is currently but distant hope that treatment alone will lead to removal and eradication. In our view, removal and eradication will happen only with a vaccine, which, necessarily, will markedly reduce the daunting difficulties of behavior and logistics of delivery and monitoring. However, achieving effective vaccine-mediated protection will require that we do better than nature. In HIV contamination, unlike other vaccine-preventable illnesses, natural eradication of contamination does not happen; viral integration into the host chromosome makes any contamination lifelong, even in the setting of fully suppressive antiretroviral therapy.5 The challenges to achieving a protective vaccine are readily apparent given the results of HIV vaccine efficacy studies to date.6 In 30 years, only 3 vaccine concepts have been testedalready a paltry numberand all have either failed or shown signals of possible protection far below the level that would be needed to impact the epidemic.7,8,9 The correlates of protection remain unknown, and there is yet to T be an immunogen available and tested that mimics the natural trimeric form of the HIV envelope on viable virions. New persons needing treatment outpace our ability to place people on therapy globally. Lack of impact of HSV treatment around the HSV epidemic10 provides a sobering reminder that therapy PF 431396 alone may not provide the required inflection point. The desperate need for an effective vaccine cannot be overstated. But you will find reasons to be optimistic. The recent successful prevention interventions with ARVs show that HIV-1 infected persons can reduce HIV transmission11 and HIV-1 uninfected persons can avoid contamination upon exposure.12 These strategies offer attractive alternatives to PF 431396 slow the epidemic, but in a practical sense, they are the opening take action for prevention while we await a vaccine that can provide safe, effective, and durable immunity to take the stage. The efficacy observed in the RV144 trial with the immunization of the canarypox/subunit protein gp120 prime-boost regimen in vaccinated Thai adults was at a low level: 26.4% (95% confidence interval [CI], ?4.0 to 47.9; P=0.08) in the intention-to-treat analysis; 26.2% (95% CI, ?13.3 to 51.9; P=0.16) in the per-protocol analysis; and 31.2% (95% CI, 1.1 to 52.1; P=0.04 by the OBrienCFleming method) in the modified intention-to-treat analysis; this result provides the best hope yet that a vaccine may one day be possible.9 As the HIV vaccine field seeks to confirm and build on the PF 431396 findings of the RV144 immune correlates analysis, we can increase the chances of future success by sharpening our focus now. We identify.