Auvert, Bertran

Dye, Christopher

Gouws, Eleanor

Korenromp, Eline L.

Schmid, George P.

Williams, Brian G.

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CORRESPONDENCE • JID 2007:195 (1 April) • 1079rural Africa: is there a difference in median timeto AIDS and survival compared with that in in-dustrialized countries? AIDS 2002; 16:597–603.6. Badri M, Lawn SD, Wood R. Short-term riskof AIDS or death in people infected with HIV-1 before antiretroviral therapy in South Africa:a longitudinal study. Lancet 2006; 368:1254–9.7. El-Sadr WM, Lundgren JD, Neaton JD, et al.CD4+ count-guided interruption of antiret-roviral treatment. N Engl J Med 2006; 355:2283–96.8. Whitworth J, Morgan D, Quigley M, et al. Ef-fect of HIV-1 and increasing immunosuppres-sion on malaria parasitaemia and clinical epi-sodes in adults in rural Uganda: a cohort study.Lancet 2000; 356:1051–6.Potential conflicts of interest: none reported.Financial support: Wellcome Trust (grant 074641 to S.D.L.); USNational Institutes of Health (grant A1058736-01A1 to R.W.).Reprints or correspondence: Dr. Stephen D. Lawn, DesmondTutu HIV Centre, Institute of Infectious Disease and MolecularMedicine, Faculty of Health Sciences, University of Cape Town,Anzio Rd., Observatory 7925, Cape Town, South Africa(stevelawn@yahoo.co.uk).The Journal of Infectious Diseases 2007;195:1078–9 2007 by the Infectious Diseases Society of America. Allrights reserved. 0022-1899/2007/19507-0023$15.00DOI: 10.1086/512164Reply to Lawn and WoodTo the Editor—Lawn and Wood [1] raisean important issue concerning the rela-tionship between CD4 cell counts andmortality in people infected with HIV andnote that there is substantial variation inCD4 cell counts at death. As CD4 cellcounts decline, the incidence of oppor-tunistic infections increases monotonically[2]; if such infections are left untreated,then people may die when their CD4 cellcounts are still relatively high, just as anHIV-negative person might. For example,in a comparison of 8 studies, the meanCD4 cell count in HIV-positive patientspresenting with tuberculosis was 202 cells/mL (range, 136–269 cells/mL) [3]. If betterdata on the time course of CD4 cell countsin a sufficiently large sample of HIV-pos-itive patients were available, more-sophis-ticated models of the relationship betweenCD4 cell count decline, the incidence ofopportunistic infections, and mortalitycould be developed. Our model, whichdraws on the limited data that are cur-rently available, is a step in this direction.It is nevertheless worth noting thatevidence from industrialized as well aslow- and middle-income countries suggeststhat the majority of AIDS-related deathsoccur at very low CD4 cell counts. Forexample, in a study in South Africa in theearly 1990s, the median CD4 cell count atthe onset of AIDS was 98 cells/mL for het-erosexual patients and 40 cells/mL for ho-mosexual patients, after which the mediansurvival time was 17 and 7 months, re-spectively [4]. In an Australian cohort fol-lowed between 1986 and 1991, the medianCD4 cell count at death was 10 cells/mL[5]. In Uganda, a recent study showed thatthe median CD4 cell count at death was24 cells/mL [6]. In the United Kingdom, astudy reported mean CD4 cell counts atdeath of 19 cells/mL in 1988, 44 cells/mLin 1997, and 58 cells/mL in 1998 [7].For the purpose of our model, the var-iation in CD4 cell counts at death is lessimportant than the variation in and levelof CD4 cell counts before HIV serocon-version, which appear to affect the rate ofCD4 cell count decline and, hence, thesurvival time after infection. A recentstudy compared CD4 cell counts in HIV-negative persons from 7 countries, and themedians varied from 599 cells/mL in Bo-tswana to 968 cells/mL in Tanzania [8]; theauthors suggested that CD4 cell count ref-erence ranges should be established forlocal populations, given the pivotal roleplayed by CD4 cell counts in decisionmaking on the initiation and monitoringof highly active antiretroviral therapy.The most important prediction of ourmodel is that the distribution of survivaltimes is independent of the initial CD4cell count, and this prediction is not sub-stantively altered if we assume a somewhathigher CD4 cell count at death. To theextent that the prediction is true, it sug-gests that, for a given person or group ofpeople, survival from a given CD4 cellcount will be longer for those whose initialCD4 cell count is low than for those inwhom it is high. More-extensive data andmore-sophisticated models could provideimportant insights into the relationshipamong CD4 cell count, the progression ofHIV infection, and mortality, as Lawn andWood suggest.Brian G. Williams,1 Eline L. Korenromp,3,5Eleanor Gouws,4 George P. Schmid,2Bertran Auvert,6,7,8 and Christopher Dye11Stop TB Department and 2HIV/AIDS Department,World Health Organization, 3The Global Fundto Fight AIDS, TB, and Malaria, and 4Policy,Evidence, and Partnerships Department, JointUnited Nations Program on HIV/AIDS, Geneva,Switzerland; 5Department of Public Health,Erasmus Medical Center, University MedicalCentre Rotterdam, Rotterdam, The Netherlands;6Institut National de la Sante´ et de la RechercheMe´dicale, Unite´ 687, and 7University of Versailles–Saint Quentin, Faculte´ de Me´decine Paris-Ile-de-France-Ouest, Saint Maurice, and 8AP-HP,Hoˆpital Ambroise Pare, Boulogne, FranceReferences1. Lawn SD, Wood R. CD4 cell count distributionsand HIV-associated mortality in Africa. J InfectDis 2007; 195:1078–9 (in this issue).2. Freedberg KA, Losina E, Weinstein MC, et al.The cost effectiveness of combination antiret-roviral therapy for HIV disease. N Engl J Med2001; 344:824–31.3. Williams BG, Dye C. Antiretroviral drugs fortuberculosis control in the era of HIV/AIDS.Science 2003; 301:1535–7.4. Maartens G, Wood R, O’Keefe E, Byrne C. In-dependent epidemics of heterosexual and ho-mosexual HIV infection in South Africa—sur-vival differences. QJM 1997; 90:449–54.5. Mills GD, Jones PD. Relationship betweenCD4 lymphocyte count and AIDS mortality,1986–1991. AIDS 1993; 7:1383–6.6. Siika AM. Predictors of mortality in HIV-in-fected adult African patients receiving highly ac-tive antiretroviral therapy [abstract MoPdb04].In: Program and abstracts of the 16th Inter-national AIDS Conference (Toronto). Geneva:International AIDS Society, 2006.7. Porter K. Changes in mean CD4 cell count atdeath in persons with known duration of HIVinfection [abstract TuPeC3330]. In: Programand abstracts of the 13th International AIDSConference (Durban, South Africa). Geneva:International AIDS Society, 2000.8. Bussmann H, Wester CW, Masupu KV, et al.Low CD4+ T-lymphocyte values in human im-munodeficiency virus-negative adults in Botswa-na. Clin Diagn Lab Immunol 2004; 11:930–5.Potential conflicts of interest: none reported.Reprints or correspondence: Dr. Brian G. Williams, World HealthOrganization, WHO/CDS/HTM/STB/TME, 20 Ave. Appia, Ge-neva 1211, Switzerland (williamsbg@who.int).The Journal of Infectious Diseases 2007;195:1079 2007 by the Infectious Diseases Society of America. Allrights reserved. 0022-1899/2007/19507-0024$15.00DOI: 10.1086/512165

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