What Risk of Death Would People Take to be Cured of HIV, and Why? A Survey of People Living With HIV

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured

What Risk of Death Would People Take to be Cured of HIV, and Why? A Survey of People Living With HIV

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured

Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits

The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Throug

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Plasma insulin-like growth factor 1 is positively associated with low-grade prostate cancer in the Health Professionals Follow-up Study 1993-2004

The insulin-like growth factor (IGF) axis plays a role in growth and progression of prostate cancer. High circulating IGF-1 levels have been associated with an increased risk of prostate cancer. Results for IGF binding protein 3 (IGFBP-3) are inconclusive. Some studies have indicated that the positive association with IGF-1 is observed only for low-grade prostate cancer (Gleason sum < 7). We previously reported in the Health Professionals Follow-up Study (HPFS) a direct positive association between ELISA-measured plasma IGF-1 and IGFBP-3 and risk of prostate cancer (462 cases diagnosed after providing a blood specimen (between 1993 and 1995), but before February 1998). With additional follow-up through January 31st 2004, and 1,331 case-control pairs in total, we were now able to investigate low-grade (Gleason sum < 7, n = 635) and high-grade (Gleason sum ≥ 7, n = 515) prostate cancer separately. Matched odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. ORs of total prostate cancer comparing top to bottom quartiles were 1.41 (95% CI 1.12-1.78, p-trend = 0.001) for IGF-1 and 1.58 (95% CI 1.24-2.01, p-trend = 0.003) for IGFBP-3. IGF-1 was more strongly associated with low-grade (OR = 1.61 top versus bottom quartile, 95% CI 1.16-2.25, p-trend = 0.01), than with high-grade (OR = 1.29, 95% CI 0.89-1.88, p-trend = 0.12) prostate cancer (p-heterogeneity = 0.08). We hypothesize that these findings reflect that high-grade prostate cancers are more autonomous, and, thus, less sensitive to the action of IGF-1 than low-grade cancers

Prediagnostic plasma IGFBP-1, IGF-1 and risk of prostate cancer

Insulin-like growth factor (IGF)-1 is associated with a higher risk of prostate cancer. IGF-binding protein (IGFBP)-1, a marker for insulin activity, also binds IGF-1 and inhibits its action. Data on IGFBP-1 and prostate cancer risk are sparse and whether the IGF and insulin axes interact to affect prostate cancer carcinogenesis is unknown. We evaluated the independent and joint influence of prediagnostic plasma levels of IGFBP-1 (fasting) and IGF-1 on risk of prostate cancer among 957 cases and 1,021 controls with fasting levels of IGFBP-1 and 1,709 cases and 1,778 controls with IGF-1 nested within the Health Professionals Follow-up Study. Unconditional logistic regression adjusting for matching factors was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Higher prediagnostic fasting IGFBP-1 levels were associated with lower risk of prostate cancer (highest vs. lowest quartile OR = 0.67, 95% CI 0.52-0.86, ptrend  = 0.003), which remained similar after adjusting for IGF-1. Prediagnostic IGF-1 was associated with increased risk of prostate cancer (highest vs. lowest quartile OR = 1.28, 95% CI = 1.05-1.56, ptrend  = 0.01). The associations with each marker were primarily driven by lower-grade and non-advanced prostate cancer. Being low in IGFBP-1 and high in IGF-1 did not confer appreciable additional risk (pinteraction  = 0.42). In summary, prediagnostic fasting IGFBP-1 may influence prostate cancer carcinogenesis. Being low in IGFBP-1 or high in IGF-1 is sufficient to elevate the risk of prostate cancer

Potential Applications for Circulating Tumor Cells expressing the Insulin Growth Factor-I Receptor

Purpose: To detect insulin-like growth factor-IR (IGF-IR) on circulating tumor cells (CTC) as a biomarker in the clinical development of a monoclonal human antibody, CP-751,871, targeting IGF-IR. Experimental Design: An automated sample preparation and analysis system for enumerating CTCs (CellTracks) was adapted for detecting IGF-IR–positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871. This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was validated using cell lines and blood samples from healthy volunteers and patients with metastatic carcinoma. Results: There was no interference between the analytic and therapeutic antibodies. Eighty patients were enrolled on phase I studies of CP-751,871, with 47 (59%) patients having CTCs detected during the study. Before treatment, 26 patients (33%) had CTCs, with 23 having detectable IGF-IR–positive CTCs. CP-751,871 alone, and CP-751,871 with cytotoxic chemotherapy, decreased CTCs and IGF-IR–positive CTCs; these increased toward the end of the 21-day cycle in some patients, falling again with retreatment. CTCs were commonest in advanced hormone refractory prostate cancer (11 of 20). Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by >50% (6 of 10 versus 2 of 8 patients). A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by >50%. Conclusions: IGF-IR expression is detectable by immunofluorescence on CTCs. These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection, particularly in advanced prostate cancer