Risk of cancers during interrupted antiretroviral therapy in the SMART study

Silverberg, Michael J.; Neuhaus, Jacqueline; Bower, Mark; Gey, Daniela; Hatzakis, Angelos; Henry, Keith; Hidalgo, José A.; Lourtau, Leonardo; Neaton, James D.; Tambussi, Giuseppe; Abrams, Donald I.

doi:10.1097/qad.0b013e3282ed6338

Cited by 120 publications

(89 citation statements)

References 35 publications

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“…In our study, the absence of any antiretroviral treatment for 3 months or more was associated with an eight-fold increased KS risk, thus confirming the danger of treatment interruption already reported with respect to progression to AIDS or death (Holkmann et al, 2007). Significantly higher KS incidence among PWHA who were assigned to the CD4 cell-guided intermittent antiretroviral treatment arm than those assigned to the continuous treatment arm was also shown in a randomised clinical trial (Silverberg et al, 2007).…”

Section: Discussionsupporting

confidence: 74%

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

et al. 2008

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Between 1984 and 2006, 12 959 people with HIV/AIDS (PWHA) in the Swiss HIV Cohort Study contributed a total of 73 412 person-years (py) of follow-up, 35 551 of which derived from PWHA treated with highly active antiretroviral therapy (HAART). Five hundred and ninety-seven incident Kaposi sarcoma (KS) cases were identified of whom 52 were among HAART users. Cox regression was used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI). Kaposi sarcoma incidence fell abruptly in 1996 -1998 to reach a plateau at 1.4 per 1000 py afterwards. Men having sex with men and birth in Africa or the Middle East were associated with KS in both non-users and users of HAART but the risk pattern by CD4 cell count differed. Only very low CD4 cell count (o50 cells ml À1 ) at enrolment or at HAART initiation were significantly associated with KS among HAART users. The HR for KS declined steeply in the first months after HAART initiation and continued to be low 7 -10 years afterwards (HR, 0.06; 95% CI, 0.02 -0.17). Thirty-three out of 52 (63.5%) KS cases among HAART users arose among PWHA who had stopped treatment or used HAART for less than 6 months.

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Section: Discussionsupporting

confidence: 74%

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

et al. 2008

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“…Although this study is not based on a strategic trial, and cannot establish that increasing the CD4 counts after starting cART caused the decrease in non-AIDS-defining malignancies, it does suggest that earlier treatment may be beneficial for reducing the incidence of non-AIDS-defining malignancies. This is supported also by recent data from the Strategies for Management of Antiretroviral Therapy study, where patients in the drug conservation arm who interrupted treatment had a higher rate of AIDS-defining malignancies, 47 which was thought to be because of lower CD4 cell counts and higher viral loads. The Strategic Timing of Antiretroviral Therapy trial to determine whether starting cART early (before CD4 drops to <500 cells/mm 3 ), rather than waiting until CD4 drops to <350 cells/mm 3 as current guidelines recommend, reduces the occurrence of serious morbidity and mortality, will also explore whether cART protects against non-AIDS-defining malignancies.…”

Section: Discussionmentioning

confidence: 58%

Relationship between current level of immunodeficiency and non‐acquired immunodeficiency syndrome‐defining malignancies

Reekie

Kósa

Engsig

et al. 2010

Cancer

129

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BACKGROUND:In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non-AIDS-defining malignancies. METHODS: A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virusrelated, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS-defining malignancies. RESULTS: A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7); 172 (48.3%) were virusrelated, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non-AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling; 95% CI, 0.75-0.88; P < .0001) and non-virus-related epithelial non-AIDSdefining malignancies (IRR, 0.84; 95% CI, 0.75-0.95; P ¼ .004), but not with other non-AIDS-defining malignancies (IRR, 1.04; 95% CI, 0.83-1.31; P ¼ .73). Current CD4 count was also associated with anal cancer (IRR, 0.86; 95% CI, 0.75-0.99; P ¼ .03), Hodgkin lymphoma (n ¼ 52; IRR, 0.83; 95% CI, 0.73-0.95; P ¼ .005), and lung cancer (IRR, 0.76; 95% CI, 0.64-0.90; P ¼ .0002). CONCLUSIONS: A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed. Cancer 2010;116:5306-15.

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“…The most common malignancies were anal cancer, basal cell carcinoma, Hodgkin’s lymphoma, and lung cancer. Although other HIV-infected cohort studies have reported similar observations [4,8,23] and suggest that the incidence of NADC is on the rise in the potent ART era [4,8], the longitudinal and robust nature of the ACTG database provided a unique opportunity to examine predisposing factors for cancer. Indeed inclusion of ART-naïve patients starting ART provided important information on factors associated with an increased risk of NADCs among HIV-infected patients.…”

Section: Discussionmentioning

confidence: 90%

Incidence of Non-AIDS-Defining Cancer in Antiretroviral Treatment-Naïve Subjects after Antiretroviral Treatment Initiation: An ACTG Longitudinal Linked Randomized Trials Analysis

et al. 2011

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Background: Prospective data on factors associated with the non-AIDS-defining cancer (NADC) incidence in HIV-infected individuals are limited. Methods: We examined the NADC incidence in 3,158 antiretroviral treatment (ART)-naïve subjects after ART initiation in AIDS Clinical Trials Group trials; extended follow-up was available for 2,122 subjects. Poisson regression was used to examine the associations between covariates and incident NADC. Results: At ART initiation, subjects (median age 37 years) were 40% non-Hispanic whites, and 82% were male; 23% had CD4+ T cell count ≤50 cells/mm³ and 25% had CD4 >350 cells/mm³. Median follow-up was 3.8 years. Among 64 incident NADCs, the most common were 8 anal cancers, 8 basal cell carcinomas, 8 Hodgkin’s disease, and 6 lung cancers. In univariate models, age, smoking and recent (time-updated) CD4 were associated with incident NADC. There was no association between initial ART drug class (protease inhibitor, nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor) and NADC. After adjusting for age, race and sex: smoking [relative risk = 2.12 (95% CI = 1.1–4.08)] and recent CD4 (≤50 cells/mm³: 3.58, 1.22–10.45; 51–200 cells/mm³: 2.54, 1.30–5.0; 201–350 cells/mm³: 2.37, 1.32–4.26 vs. >350 cells/mm³) were associated with NADC. Conclusion: Smoking and lower recent CD4 levels, but not initial ART drug class, were associated with NADC. Strategies for maintaining higher CD4 cell counts and successful smoking cessation may reduce the NADC incidence in the HIV-infected population.

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Risk of cancers during interrupted antiretroviral therapy in the SMART study

Abstract: Non-AIDS-defining malignancies were more common in this cohort than AIDS-defining malignancies. This analysis provides further evidence against the use of CD4 T-cell-guided ART because of a higher risk of AIDS-defining malignancies in addition to opportunistic infections and deaths.

Cited by 120 publications

References 35 publications

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Kaposi sarcoma incidence in the Swiss HIV Cohort Study before and after highly active antiretroviral therapy

Relationship between current level of immunodeficiency and non‐acquired immunodeficiency syndrome‐defining malignancies

Incidence of Non-AIDS-Defining Cancer in Antiretroviral Treatment-Naïve Subjects after Antiretroviral Treatment Initiation: An ACTG Longitudinal Linked Randomized Trials Analysis

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