Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Franceschi S
PROVIDER: S-EPMC2920013 | biostudies-other | 2010 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Highly active antiretroviral therapy (HAART) has proved efficient in increasing CD4 counts in many randomized clinical trials. Because randomized trials have some limitations (e.g., short duration, highly selected subjects), it is interesting to assess the effect of treatments using observational studies. This is challenging because treatment is started preferentially in subjects with severe conditions. This general problem had been treated using Marginal Structural Models (MSM) relying on the counterfactual formulation. Another approach to causality is based on dynamical models. We present three discrete-time dynamic models based on linear increments models (LIM): the first one based on one difference equation for CD4 counts, the second with an equilibrium point, and the third based on a system of two difference equations, which allows jointly modeling CD4 counts and viral load. We also consider continuous-time models based on ordinary differential equations with non-linear mixed effects (ODE-NLME). These mechanistic models allow incorporating biological knowledge when available, which leads to increased statistical evidence for detecting treatment effect. Because inference in ODE-NLME is numerically challenging and requires specific methods and softwares, LIM are a valuable intermediary option in terms of consistency, precision, and complexity. We compare the different approaches in simulation and in illustration on the ANRS CO3 Aquitaine Cohort and the Swiss HIV Cohort Study.
| S-EPMC5269533 | biostudies-literature
Project description:BackgroundSexually transmitted infections (STIs) are common among people with human immunodeficiency virus (PWH), but there are limited data about risk factors and incidence of STIs in large, representative cohort studies.MethodsWe assessed incidence and risk factors of STIs reported by treating physicians within the Swiss HIV Cohort Study (SHCS). Sexually transmitted infections and demographic, clinical, and behavioral characteristics were prospectively collected at 6-month follow-up visits between October 2017 and November 2019. We used multilevel Poisson regression to assess incidence rate ratios of different STIs.ResultsAmong 10 140 study participants, a total of 1634 STIs in 1029 SHCS participants were reported over 17 766 person-years of follow up (PYFUP). The overall incidence of any reported STI was 91.9 per 1000 PYFU (95% confidence interval [CI], 85.8 -98.5). Among the 1634 STI episodes, there were 573 (35.1%) incident cases of syphilis, 497 gonorrhea (30.4%), and 418 chlamydia (25.6%). Men who have sex with men (MSM) younger than 50 years represented 21% of the study population, but accounted for 61% of reported STIs. Male sex (adjusted incidence rate ratio [aIRR], 2.03; 95% CI, 1.36-3.02), MSM (aIRR, 3.62; 95% CI, 2.88-4.55), age group 18-34 years (aIRR, 1.78; 95% CI, 1.51-2.10), history of sexual relationships with occasional partners (aIRR, 6.87; 95% CI, 5.40-8.73), and reporting injecting drug use (aIRR, 2.48; 95% CI, 1.91-3.23) were associated with a higher risk of incident STIs.ConclusionsSexually transmitted infections were frequent among PWH and varied considerably between age and risk groups. Screening programs and recommendations for STI testing need to be adapted according to risk factors and demographic characteristics.
| S-EPMC9728517 | biostudies-literature
Project description:Non-AIDS-defining cancers (NADCs) have emerged as significant contributors to cancer mortality and morbidity among persons living with HIV (PLWH). Because NADCs are also associated with many social and behavioural risk factors that underlie HIV, determining the extent to which each of these factors contributes to NADC risk is difficult. We examined cancer incidence and mortality among persons with a history of incarceration, because distributions of other cancer risk factors are likely similar between prisoners living with HIV and non-infected prisoners.Registry-based retrospective cohort study.Cohort of 22,422 persons incarcerated in Georgia, USA, prisons on 30 June 1991, and still alive in 1998.Cancer incidence and mortality were assessed between 1998 and 2009, using cancer and death registry data matched to prison administrative records. Age, race and sex-adjusted standardised mortality and incidence ratios, relative to the general population, were calculated for AIDS-defining cancers, viral-associated NADCs and non-infection-associated NADCs, stratified by HIV status.There were no significant differences in cancer mortality relative to the general population in the cohort, regardless of HIV status. In contrast, cancer incidence was elevated among the PLWH. Furthermore, incidence of viral-associated NADCs was significantly higher among PLWH versus those without HIV infection (standardised incidence ratio=6.1, 95% CI 3.0 to 11.7, p<0.001).Among PLWH with a history of incarceration, cancer incidence was elevated relative to the general population, likely related to increased prevalence of oncogenic viral co-infections. Cancer prevention and screening programmes within prisons may help to reduce the cancer burden in this high-risk population.
| S-EPMC4838674 | biostudies-other
Project description: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 (<50 cells microl(-1)) at enrollment 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.
| S-EPMC2528138 | biostudies-other
Project description:We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients.
2011-03-26 | GSE28177 | GEO
Project description:ObjectivesThe extent to which highly active antiretroviral therapy (HAART) era cognitive disorders are due to active processes, incomplete clearance of reservoirs, or comorbidities is controversial. This study aimed to determine if immunologic and virologic factors influence cognition after first-time HAART in Thai individuals with HIV-associated dementia (HAD) and Thai individuals without HAD (non-HAD).MethodsVariables were captured longitudinally to determine factors predictive of degree of cognitive recovery after first-time HAART. Neuropsychological data were compared to those of 230 HIV-negative Thai controls.ResultsHIV RNA and CD4 lymphocyte counts were not predictive of HAD cross-sectionally or degree of cognitive improvement longitudinally. In contrast, baseline and longitudinal HIV DNA isolated from monocytes correlated to cognitive performance irrespective of plasma HIV RNA and CD4 lymphocyte counts pre-HAART (p < 0.001) and at 48 weeks post HAART (p < 0.001). Levels exceeding 3.5 log(10) copies HIV DNA/10(6) monocyte at baseline distinguished all HAD and non-HAD cases (p < 0.001). At 48 weeks, monocyte HIV DNA was below the level of detection of our assay (10 copies/10(6) cells) in 15/15 non-HAD compared to only 4/12 HAD cases, despite undetectable plasma HIV RNA in 26/27 cases. Baseline monocyte HIV DNA predicted 48-week cognitive performance on a composite score, independently of concurrent monocyte HIV DNA and CD4 count (p < 0.001).ConclusionsMonocyte HIV DNA level correlates to cognitive performance before highly active antiretroviral therapy (HAART) and 48 weeks after HAART in this cohort and baseline monocyte HIV DNA may predict 48-week cognitive performance. These findings raise the possibility that short-term incomplete cognitive recovery with HAART may represent an active process related to this peripheral reservoir.
| S-EPMC2677463 | biostudies-literature
Project description:We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4 T cells in peripheral blood was observed, while gut mucosal CD4 T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Gut mucosal responses to HAART interruption were evaluated with Affymetrix arrays
2011-03-25 | E-GEOD-28177 | biostudies-arrayexpress
Project description:OBJECTIVE:Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A cliniconeurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. SUBJECTS AND ASSAYS: HIV gag/pol RNA and DNA copies were quantified with reverse transcriptase-polymerase chain reaction or polymerase chain reaction in 148 HAART-era brain specimens. Comparison with HAND, HIVE, and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman tests, respectively. RESULTS:Brain HIV RNA was higher in subjects with HAND plus HIVE versus without HAND (delta = 2.48 log10 units, n = 27 versus 36, P < 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different versus without HAND (P = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (P < 0.001) but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (P < 0.01) and much lower versus with HIVE (P < 0.001). CONCLUSIONS:Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE, and these patients could obtain added NP improvement by further reducing brain HIV while on HAART. Patients not in those groups are less certain to obtain added NP benefit.
| S-EPMC3664102 | biostudies-literature
Project description:ObjectivesWe aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in Switzerland.MethodsThis was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause.ResultsOf all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation.ConclusionsThe median age of women living with HIV at menopause is around 2 years lower than that reported for HIV-negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause-associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy.
| S-EPMC9306735 | biostudies-literature
Project description:BackgroundNo study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART).MethodsEligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality.ResultsOver a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/μL experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOIs (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/μL at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12.59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64).ConclusionsDespite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.
| S-EPMC6064097 | biostudies-literature