J Acquir Immune Defic Syndr Volume 63, Number 5, August 15, 2013 13. De Luca A, Doino M, Fabbiani M, et al. Treatment simplification to atazanavir/ritonavir plus lamivudine QD in patient on two NRTIs plus atazanavir/ritonavir with optimal virologic control: 48 weeks safety and efficacy result from a pilot study (Atazanavir and Lamivudine Simplification study) [abstract]. Presented at 6th International AIDS Society Conference; 2011. CDB357. 14. Rossotti R, Moioli MC, Chianura L, et al. Lamivudine or emtricitabine (XTC)/protease inhibitor dual therapy as a harm-reduction strategy inpatients with tenofovir-related renal toxicity: a case-control study. Scand J Infect Dis. 2012;44:879–883. 15. Yeni P. 2010 Report on the Medical Management of HIV infected people, under the direction of Prof. Patrick Yeni. Paris, France: La documentation Francaise; 2010. 16. Read PJ, Mandalia S, Khan P, et al. When should HAART be initiated in pregnancy to achieve an undetectable HIV viral load by delivery? AIDS. 2012;26:1095–1103. 17. Sulkowski MS. Hepatotoxicity associated with antiretroviral therapy containing HIV-1 protease inhibitors. Semin Liver Dis. 2003; 23:183–194. 18. Sulkowski MS, Mehta SH, Chaisson RE, et al. Hepatotoxicity associated with protease inhibitorbased antiretroviral regimens with or without concurrent ritonavir. AIDS. 2004;18:2277–2284. 19. Bonfanti P, Ricci E, Penco G, et al. Low incidence of hepatotoxicity in a cohort of HIV patients treated with lopinavir/ritonavir. AIDS. 2005;19:1433–1434. 20. Spengler U. Hepatic toxicity of antiviral agents. In: Kaplowitz N, DeLeve LD, eds. DrugInduced Liver Disease. 2nd ed. New York, NY: Informa Healthcare USA; 2007:567–591. 21. Warszawski J, Tubiana R, Le Chenadec J, et al. Mother-to-child HIV transmission despite antiretroviral therapy in the ANRS French Perinatal Cohort. AIDS. 2008;22:289–299.
Invasive Cervical Cancer Risk Among HIV-Infected Women Is a Function of CD4 Count and Screening To the Editors: The letter to the editor by Nazac et al1 highlights the following important issue: the effectiveness of screening and treatment of precancerous lesions in preventing invasive cervical cancer Supported by grants from the National Institutes of Health U01-AI-35043, U01-AI-42590, U01AI-069918, R01DE021395 (G.D.), and R01 CA085178 (H.D.S.). The authors have no conflicts of interest to disclose.
Ó 2013 Lippincott Williams & Wilkins
(ICC). One of the major findings of our study2 was that nearly all of the cases of ICC that were observed in this large prospective multicohort investigation had either not been properly screened by Pap tests or failed to appear for colposcopy and/or treatment after an abnormal Pap test. The other major finding was that the incidence of cancer increased monotonically with diminishing CD4+ count among the HIV-infected women, a biologic gradient that persisted after adjustment for covariates in multivariate analyses. From a scientific perspective, the biologic gradient between CD4+ count and ICC risk provides strong evidence of a biologic relationship between host immune status and the incidence of ICC in HIV-infected women. This is an important finding from a clinical and biologic perspective. Although the relation of low CD4+ count with cervical precancer in HIV-infected women has been well established,3,4 there was a paucity of appropriate similar data regarding ICC as an outcome. Through the collaborative efforts of multiple observational cohorts to combine their data, we were able to conduct the first study of the CD4+ count—ICC relationship in HIVinfected women in North America. Nazac et al1 suggest that it was somehow unethical and wrong from a research perspective for the women who failed to receive adequate Pap testing or follow-up with colposcopy and/ or treatment to be included in these cohorts or in our analysis. Instead, they suggest what amounts to a “per-protocol” analysis, which is an analysis in which data only amongst those who followed protocol are examined. However, that misses the point of observational cohort research, which is to reflect real world circumstances, and not the rarefied world of clinical trials. In the real world, patients sometimes unavoidably or by choice do not appear for proper follow-up. Our data suggest that in immunocompromised HIV-infected women this is especially risky because those with CD4 ,200 cells at study entry had a 3-fold higher risk of ICC compared with those with CD4 $350 and almost 8-fold higher risk compared with similarly followed HIV-uninfected women.
Letters to the Editor
Alison G. Abraham, PhD, MHS, MS* Howard D. Strickler, MD† Gypsyamber D’Souza, PhD* *Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD †Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY
REFERENCES 1. Nazac A, Fridmann S, Boufassa F. Is the level of proof of the North American multicohort collaboration prospective study sufficient to conclude that incidence of invasive cervical cancer is higher in HIV–infected women? J Acquir Immune Defic Syndr. 2013;63:e163. 2. Abraham AG, Strickler HD, Jing Y, et al, for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA. Invasive cervical cancer risk among HIV-infected women: a North American multicohort collaboration prospective study. J Acquir Immune Defic Syndr. 2012 Dec 18. [Epub ahead of print] PMCID: PMC3633634. 3. Harris TG, Burk RD, Palefsky JM, et al. Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results. JAMA. 2005;293:1471–1476. 4. Strickler HD, Palefsky JM, Shah KV, et al. Human papillomavirus type 16 and immune status in human immunodeficiency virus-seropositive women. J Natl Cancer Inst. 2003;95:1062–1071.
Is the Level of Proof of the North American Multicohort Collaboration Prospective Study Sufficient to Conclude That Incidence of Invasive Cervical Cancer is Higher in HIV-Infected Women? To the Editors: Abraham et al have demonstrated that invasive cervical cancer (ICC) is more common in HIV-positive women. They strongly suggest that the risk of cervical The authors have no funding or conflicts of interest to disclose.
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Invasive Cervical Cancer Risk Among HIV-Infected Women Is a Function of CD4 Count and Screening To the Editors: The letter to the editor by Nazac et al1 highlights the following important issue: the effectiveness of screening and treatment of precancerous lesions in preventing invasive cervical cancer Supported by grants from the National Institutes of Health U01-AI-35043, U01-AI-42590, U01AI-069918, R01DE021395 (G.D.), and R01 CA085178 (H.D.S.). The authors have no conflicts of interest to disclose.
Ó 2013 Lippincott Williams & Wilkins
(ICC). One of the major findings of our study2 was that nearly all of the cases of ICC that were observed in this large prospective multicohort investigation had either not been properly screened by Pap tests or failed to appear for colposcopy and/or treatment after an abnormal Pap test. The other major finding was that the incidence of cancer increased monotonically with diminishing CD4+ count among the HIV-infected women, a biologic gradient that persisted after adjustment for covariates in multivariate analyses. From a scientific perspective, the biologic gradient between CD4+ count and ICC risk provides strong evidence of a biologic relationship between host immune status and the incidence of ICC in HIV-infected women. This is an important finding from a clinical and biologic perspective. Although the relation of low CD4+ count with cervical precancer in HIV-infected women has been well established,3,4 there was a paucity of appropriate similar data regarding ICC as an outcome. Through the collaborative efforts of multiple observational cohorts to combine their data, we were able to conduct the first study of the CD4+ count—ICC relationship in HIVinfected women in North America. Nazac et al1 suggest that it was somehow unethical and wrong from a research perspective for the women who failed to receive adequate Pap testing or follow-up with colposcopy and/ or treatment to be included in these cohorts or in our analysis. Instead, they suggest what amounts to a “per-protocol” analysis, which is an analysis in which data only amongst those who followed protocol are examined. However, that misses the point of observational cohort research, which is to reflect real world circumstances, and not the rarefied world of clinical trials. In the real world, patients sometimes unavoidably or by choice do not appear for proper follow-up. Our data suggest that in immunocompromised HIV-infected women this is especially risky because those with CD4 ,200 cells at study entry had a 3-fold higher risk of ICC compared with those with CD4 $350 and almost 8-fold higher risk compared with similarly followed HIV-uninfected women.
Letters to the Editor
Alison G. Abraham, PhD, MHS, MS* Howard D. Strickler, MD† Gypsyamber D’Souza, PhD* *Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD †Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY
REFERENCES 1. Nazac A, Fridmann S, Boufassa F. Is the level of proof of the North American multicohort collaboration prospective study sufficient to conclude that incidence of invasive cervical cancer is higher in HIV–infected women? J Acquir Immune Defic Syndr. 2013;63:e163. 2. Abraham AG, Strickler HD, Jing Y, et al, for the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA. Invasive cervical cancer risk among HIV-infected women: a North American multicohort collaboration prospective study. J Acquir Immune Defic Syndr. 2012 Dec 18. [Epub ahead of print] PMCID: PMC3633634. 3. Harris TG, Burk RD, Palefsky JM, et al. Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results. JAMA. 2005;293:1471–1476. 4. Strickler HD, Palefsky JM, Shah KV, et al. Human papillomavirus type 16 and immune status in human immunodeficiency virus-seropositive women. J Natl Cancer Inst. 2003;95:1062–1071.
Is the Level of Proof of the North American Multicohort Collaboration Prospective Study Sufficient to Conclude That Incidence of Invasive Cervical Cancer is Higher in HIV-Infected Women? To the Editors: Abraham et al have demonstrated that invasive cervical cancer (ICC) is more common in HIV-positive women. They strongly suggest that the risk of cervical The authors have no funding or conflicts of interest to disclose.
www.jaids.com |
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