We declare that we have no conflicts of interest.
*Nina Schwalbe, Ibrahim El-Ziq [email protected]
Performance & Policy, GAVI Alliance, 1202 Geneva, Switzerland (NS); and Immunization Centre, UNICEF, New York, NY, USA (IEZ) 1
Usher AD. Dispute over pneumococcal vaccine initiative. Lancet 2009; 374: 1879–80.
Early initiation of treatment for HIV infection On Dec 1, 2009, the US Department of Health and Human Services (DHHS) issued updated guidelines for treatment of HIV infection,1 which include the statement that “the Panel recommends antiretroviral therapy in patients with CD4 counts between 350 and 500 cells/mm3”. The data cited in support of this statement are from two large collaborative analyses of data from observational studies, from ART CC2 and www.thelancet.com Vol 375 February 20, 2010
NA ACCORD.3 A randomised trial still in progress (START)4 is randomising people with a CD4 cell count of greater than 500 per μL to either start antiretroviral therapy (ART) immediately or defer to a CD4 cell count of 350 per μL. We are concerned that some may interpret the new recommendations as implying that the deferral group of this trial is no longer ethical. Such an interpretation would endanger the future of the trial in the USA. As investigators involved in analysis of observational studies, we would like to give our interpretation of the available data. An analysis from ART CC cited by the Panel suggests that deferring therapy until the 251–350 cells per μL range was associated with a higher rate of progression to AIDS and death than was starting therapy in the 351–450 cells per μL range (hazard ratio 1·28, 95% CI 1·04–1·57).2 We would point out that, in the equivalent analysis with mortality as endpoint, the estimated hazard ratio was 1·13 (95% CI 0·80–1·60). For the comparison of deferring therapy until the 351–450 cells per μL range, compared with starting therapy in the 451–550 cells per μL range, the estimated hazard ratio was below 1 (0·93, 0·60–1·44). The second analysis cited, from NA ACCORD,3 found higher hazard ratios apparently favouring early ART initiation, but there are unresolved questions about whether there is a bias in the analysis favouring early ART.5 Additionally, as pointed out in the DHHS guidelines, interpretation of all analyses from observational studies is limited by the potential for bias due to unmeasured confounders, which could plausibly explain the eﬀects seen. We therefore do not believe that there is convincing evidence to conclude that deferral of initiation of ART to a CD4 count of 350 per μL causes net harm, particularly in terms of mortality, compared with starting at any higher level. We strongly support continued enrolment into START. Large randomised studies represent the only means of
eventually obtaining the deﬁnitive result we need to properly inform future patient care. AP is a statistician involved in the INSIGHT START trial. DC, CS, and JS have no conﬂicts of interest.
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contribution would increase to $4 for a limited number of doses to fund the committed $7 price. This change in the donor contribution would not aﬀect the number of children vaccinated. Rather it would only increase the speed at which the total donor contribution, of $1·5 billion, is paid out. A $3·50 price cap was recommended on the basis of expert review of cost of goods and manufacturing processes. This was the best estimate of the lowest possible price that would still encourage participation of multiple manufacturers. When supply agreements are signed with vaccine manufacturers, the vaccine could be delivered in GAVI-eligible countries as early as 2010 at an unprecedented price reduction compared to the price of currently available pneumococcal vaccine in developed countries. The right to vaccination and protection from a preventable disease is a right for every child.
*Andrew Phillips, Dominique Costagliola, Caroline Sabin, Jonathan Sterne [email protected]
University College London, London NW3 2PF, UK (AP, CS); l’U943 INSERM and Université Pierre et Marie Curie, Paris, France (DC); and University of Bristol, Bristol, UK (JS) 1
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. http://www.aidsinfo.nih. gov/ContentFiles/AdultandAdolescentGL.pdf (accessed Feb 3, 2010). Sterne JA, May M, Costagliola D, et al. Timing of initiation of antiretroviral therapy in AIDSfree HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009; 373: 1352–63. Kitahata MM, Gange SJ, Abraham AG, et al. Eﬀect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009; 360: 1815–26. INSIGHT START trial. http://insight.ccbr.umn. edu/start/ (accessed Feb 3, 2010). Hernan MA, Robins JM. Early versus deferred antiretroviral therapy for HIV. N Engl J Med 2009; 361: 822–24.
HPV vaccination: waiting for evidence of eﬀectiveness As noted by Gary Cliﬀord (Dec 12, p 1948),1 the greatest source of uncertainty about the potential eﬀectiveness of human papillomavirus (HPV) vaccines remains the duration of the immune response. However, even if the most optimistic scenario of HPV vaccine eﬀectiveness is realised, the introduction of HPV vaccines to populations not yet fully covered by screening services may compete with limited budgets for the buildout of screening services and thereby decelerate global reductions in deaths from cervical cancer by creating populations of women who will not be protected by either screening or vaccination.2 639
The printed journal includes an image merely for illustration
Moreover, the most optimistic scenario of HPV vaccine eﬀectiveness may not be realised: we will not know for many more years whether HPV vaccination will prevent cancer or, in the worst case, do harm;3 and leading scientists, including Nobel laureate Harald zur Hausen,4 predict that even the best-case scenario of HPV vaccination will require booster doses. In matters pertaining to life and death, it is essential to choose the sure thing, and, by deﬁnition, dangerous to choose otherwise. With regard to cervical cancer prevention, Papanicolaou cytological screening, done correctly, is a sure thing; HPV vaccination, done correctly, is not. We must not allow our hopes to cloud these observations. Therefore, developing countries should allocate their limited resources to cervical screening, rather than HPV vaccination, until the possibility has been excluded that HPV vaccines may be ineﬀective for cervical cancer prevention, or until full coverage of target demographic groups by screening services has been achieved, whichever comes ﬁrst.5 We declare that we have no conﬂicts of interest.
*Eric J Suba, Stephen S Raab, on behalf of the Viet/American Cervical Cancer Prevention Project [email protected]
Department of Pathology, Kaiser Permanente Medical Center, San Francisco, CA 94115, USA (EJS); and Department of Pathology, University of Colorado Health Sciences Center, Aurora, CO, USA (SSR) 1
Clifford GM. Global access to HPV vaccination: what are we waiting for? Lancet 2009; 374: 1948–49. Suba EJ, Murphy SK, Donnelly AD, Furia LM, Huynh ML, Raab SS; Viet/American Cervical Cancer Prevention Project. Systems analysis of real-world obstacles to successful cervical cancer prevention in developing countries. Am J Public Health 2006; 96: 480–87. Haug CJ. Human papillomavirus vaccination—reasons for caution. N Engl J Med 2008; 359: 861–62. Michels KB, zur Hausen H. HPV vaccine for all. Lancet 2009; 374: 268–70. Suba EJ, Raab SS; Viet/American Cervical Cancer Prevention Project. Human papillomavirus vaccine. N Engl J Med 2007; 357: 1155.
The internet and informed dissent The parents of a 6-year-old boy awaiting a tonsillectomy in our department rang to cancel his admission on the morning of his operation. The night before his admission the little boy had searched the internet for information on tonsillectomy, and Google had led him straight to an unabridged graphic YouTube video of the operation. Not surprisingly, he concluded that he did not want the operation, and regrettably his place on the operating list could not be ﬁlled. Few would suggest that internet access to information on health matters and treatment options is disadvantageous. Many clinicians now see patients who are well informed by the internet before clinic consultations or admissions; however, optimum outcomes may not always follow. Using the same search, we were struck by how easily this YouTube ﬁlm could be reached, and how graphic was its content. We were further surprised that an adjacent link from that site took one straight into a detailed video of the residual gross anatomy after a supraglottic laryngectomy with radical neck dissection. Patients can easily access the internet to obtain health-care information before surgical procedures, but such information varies widely and highly ranked websites may not be the most reliable.1 16 million households in Great Britain (65%) had internet access in 2008.2 Use of the internet is now mastered by ever younger children, with a recent Eurobarometer poll of parents in 2008 quoting ﬁgures as high as 87% use in 6–10-year-olds in the UK in households with internet access.3 Clinicians should anticipate what eﬀect this kind of preoperative viewing may have, particularly among younger patients. Should parents now be made aware that
unrestricted access to this kind of viewing may not be in the best interests of their children, especially when preparing to bring a child into hospital to undergo elective surgery? We declare that we have no conﬂicts of interest.
*S Maskell, G Cross, P Gluckman [email protected]
Department of Otolaryngology—Head and Neck Surgery (SM, PG) and Department of Anaesthetics (GC), Medway Maritime Hospital, Windmill Road, Gillingham ME7 5NY, UK 1
Roshan A, Agarwal S, England RJ. Role of information available over the internet: what are the parents of children undergoing tonsillectomy likely to ﬁnd? Ann R Coll Surg Engl 2008; 90: 601–05. Oﬃce for National Statistics. Internet access 2008: households and individuals. http:// www.statistics.gov.uk/pdfdir/iahi0808.pdf (accessed Oct 1, 2009). Gallup. Towards a safer use of the internet for children in the EU—a parents’ perspective. http://ec.europa.eu/information_society/ activities/sip/docs/eurobarometer/ annexesanalyticalreport_2008.pdf (accessed Oct 1, 2009).
Department of Error Harris Cheng M. Cambodia criticised over unethical drug trial. Lancet 2010; 375: 187–88—In this World Report (Jan 16), the third sentence of the 13th paragraph should have read: “Korsang staﬀ said it could not be considered unless a treatment protocol was produced and reviewed by their medical doctor, unless there was evidence the medicine had been registered in Cambodia, and unless all participants had given voluntary informed consent.” Warrell DA. Snake bite. Lancet 2010; 375: 77–88—In this Seminar (Jan 2), the y-axis on ﬁgure 8 should have read: “Venom antigen (μg/L)”.
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