Incidence of HIV-related anal cancer remains increased despite long-term combined antiretroviral treatment: results from the french hospital database on HIV.

PURPOSE: To study recent trends in the incidence of anal cancer in HIV-infected patients receiving long-term combined antiretroviral treatment (cART) compared with the general population. PATIENTS AND METHODS: From the French Hospital Database on HIV, we identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. We compared incidence rates of anal cancer across four calendar periods: 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods). Standardized incidence ratios (SIRs) were calculated by using general population incidence data from the French Network of Cancer Registries. RESULTS: In HIV-infected patients, the hazard ratio (HR) in the cART periods versus the pre-cART period was 2.5 (95% CI, 1.28 to 4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6 to 1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6 to 140.3), 49.2 (95% CI, 33.2 to 70.3), and 13.1 (95% CI, 6.8 to 22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/μL for at least 2 years, SIRs were 67.5 (95% CI, 41.2 to 104.3) when the CD4 nadir was less than 200/μL for more than 2 years and 24.5 (95% CI, 17.1 to 34.1) when the CD4 nadir was more than 200/μL. CONCLUSION: Relative to that in the general population, the risk of anal cancer in HIV-infected patients is still extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM

Does accounting for gene-environment (GxE) interaction increase the power to detect the effect of a gene in a multifactorial disease?

Despite tremendous efforts, few genes involved in the susceptibility for complex disorders have been identified. One explanation is that these disorders are a result of an interaction between genes and environment, and under such conditions, it may be difficult to measure the true genetic effect without accounting for the interaction. Umbach and Weinberg ([2000] Am. J. Hum. Genet. 66:251-261) proposed an association test which looks at the joint effects of genotype and environment, using case-parent trios. In this study, we explore under which conditions accounting for GxE interaction enhances one's ability to detect the role of genetic factors in complex diseases. Using asymptotic power calculations, we investigate the power to detect the gene effect over varying exposure frequencies and different scenarios of GxE interaction. We show that for a given sample size, interaction scenario, and allele frequency, the actual gain in power while accounting for the interaction depends on the magnitude of the exposure frequency: the largest gains are seen for relatively low exposure frequencies. Moreover, a loss of power can be observed when the exposure is frequent and/or the exposure effect is strong. If we consider a gene with a disease allele frequency of 0.2, with no effect in the absence of exposure, an exposure with a 10-fold increase risk and a GxE relative risk of 2, then when the exposure frequency is 0.1, accounting for GxE interaction increases the power to detect the gene effect in 200 trios by 10%; alternatively, when the exposure frequency is 0.9, it decreases the power by 15%

Performance of the marginal structural cox model for estimating individual and joined effects of treatments given in combination

International audienceBACKGROUND:The Marginal Structural Cox Model (Cox-MSM), an alternative approach to handle time-dependent confounder, was introduced for survival analysis and applied to estimate the joint causal effect of two time-dependent nonrandomized treatments on survival among HIV-positive subjects. Nevertheless, Cox-MSM performance in the case of multiple treatments has not been fully explored under different degree of time-dependent confounding for treatments or in case of interaction between treatments. We aimed to evaluate and compare the performance of the marginal structural Cox model (Cox-MSM) to the standard Cox model in estimating the treatment effect in the case of multiple treatments under different scenarios of time-dependent confounding and when an interaction between treatment effects is present.METHODS:We specified a Cox-MSM with two treatments including an interaction term for situations where an adverse event might be caused by two treatments taken simultaneously but not by each treatment taken alone. We simulated longitudinal data with two treatments and a time-dependent confounder affected by one or the two treatments. To fit the Cox-MSM, we used the inverse probability weighting method. We illustrated the method to evaluate the specific effect of protease inhibitors combined (or not) to other antiretroviral medications on the anal cancer risk in HIV-infected individuals, with CD4 cell count as time-dependent confounder.RESULTS:Overall, Cox-MSM performed better than the standard Cox model. Furthermore, we showed that estimates were unbiased when an interaction term was included in the model.CONCLUSION:Cox-MSM may be used for accurately estimating causal individual and joined treatment effects from a combination therapy in presence of time-dependent confounding provided that an interaction term is estimated

Additional file 3: Tables S2. of Performance of the marginal structural cox model for estimating individual and joined effects of treatments given in combination

Multivariate parameter estimates for covariate association with the risk of anal cancer in HIV-infected persons: comparison of weighted Cox MSM and standard time dependent Cox models. (DOCX 22 kb

Univariable and multivariable analyzes for loss of LTNP and HIV controller status.

<p>Univariable and multivariable analyzes for loss of LTNP and HIV controller status.</p

Characteristics of LTNP and HIC patients identified in 2005 who maintained or lost their status during follow-up.

<p>Characteristics of LTNP and HIC patients identified in 2005 who maintained or lost their status during follow-up.</p

Loss of long-term non-progressor and HIV controller status over time in the French Hospital Database on HIV - ANRS CO4 - Fig 1

<p><b>Cumulative incidence of loss of LTNP (panel A) and HIV controller (panel B) status, treatment initiation and non AIDS deaths since 2005. A:</b> Long-term non-progressors (n = 171). <b>B:</b> HIV controllers (n = 72).</p

Incidence of Herpes Zoster in HIV-Infected Adults in the Combined Antiretroviral Treatment (cART) Era: Results from the FHDH-ANRS CO4 Cohort

International audienceBackground: Recent studies have shown a decrease in the incidence of herpes zoster (HZ) among HIV-infected patients since the cART era, but more data are needed on a possible increase in the risk early after cART initiation.Methods: We studied the HZ incidence and risk factors among patients followed in the French Hospital Database on HIV (FHDH) between 1992 and 2011. Standardized incidence ratios (SIR) were used for comparison with the general population between 2005 and 2008. The risk of HZ following cART initiation (0-6, ≥6 months) was studied with Poisson regression models.Results: 7167 cases of incident HZ were diagnosed among 91 044 individuals (583 125 person-years). The incidence declined significantly from 2955 per 100 000 person-years in 1992-1996 to 628 in 2009-2011. This decline was mainly explained by cART (RR=0.60; 95%CI, 0.57-0.64). The risk of HZ was associated with low CD4 cell counts, high HIV-RNA levels, low CD4/CD8 ratios and prior AIDS. Compared to the general population, the risk of HZ was higher in HIV-infected patients (overall SIR=2.7; 95%CI, 2.6-2.9), particularly between ages 15 and 45 years (SIR=4-6). In ART-naive patients a moderate increase in the HZ risk was observed during the first 6 months of cART, with a peak at 3 months (RR=1.47 95%CI, 1.26-1.73) a finding that disappeared after adjustment for the current CD4 cell count (RR=1.03; 95%CI, 0.81-1.32). Conclusions: The risk of HZ has declined markedly among HIV-infected patients in the cART era but remains 3 times higher than in the general population. The risk increases moderately during the first 6 months of cART