Changing patterns of cancer incidence in the early- and late-HAART periods: the Swiss HIV Cohort Study

The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy.

High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients

To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis.

Resurgence of HIV infection among men who have sex with men in Switzerland: mathematical modelling study

Background New HIV infections in men who have sex with men (MSM) have increased in Switzerland since 2000 despite combination antiretroviral therapy (cART). The objectives of this mathematical modelling study were: to describe the dynamics of the HIV epidemic in MSM in Switzerland using national data; to explore the effects of hypothetical prevention scenarios; and to conduct a multivariate sensitivity analysis. Methodology/Principal Findings The model describes HIV transmission, progression and the effects of cART using differential equations. The model was fitted to Swiss HIV and AIDS surveillance data and twelve unknown parameters were estimated. Predicted numbers of diagnosed HIV infections and AIDS cases fitted the observed data well. By the end of 2010, an estimated 13.5% (95% CI 12.5, 14.6%) of all HIV-infected MSM were undiagnosed and accounted for 81.8% (95% CI 81.1, 82.4%) of new HIV infections. The transmission rate was at its lowest from 1995–1999, with a nadir of 46 incident HIV infections in 1999, but increased from 2000. The estimated number of new infections continued to increase to more than 250 in 2010, although the reproduction number was still below the epidemic threshold. Prevention scenarios included temporary reductions in risk behaviour, annual test and treat, and reduction in risk behaviour to levels observed earlier in the epidemic. These led to predicted reductions in new infections from 2 to 26% by 2020. Parameters related to disease progression and relative infectiousness at different HIV stages had the greatest influence on estimates of the net transmission rate. Conclusions/Significance The model outputs suggest that the increase in HIV transmission amongst MSM in Switzerland is the result of continuing risky sexual behaviour, particularly by those unaware of their infection status. Long term reductions in the incidence of HIV infection in MSM in Switzerland will require increased and sustained uptake of effective interventions.

Hepatitis C coinfection is independently associated with decreased adherence to antiretroviral therapy in a population-based HIV cohort

OBJECTIVE: To characterize the impact of hepatitis C (HCV) serostatus on adherence to antiretroviral treatment (ART) among HIV-infected adults initiating ART. METHODS: The British Columbia HIV/AIDS Drug Treatment Program distributes, at no cost, all ART in this Canadian province. Eligible individuals used triple combination ART as their first HIV therapy and had documented HCV serology. Statistical analyses used parametric and non-parametric methods, including multivariate logistic regression. The primary outcome was > or = 95% adherence, defined as receiving > or = 95% of prescription refills during the first year of antiretroviral therapy. RESULTS: There were 1186 patients eligible for analysis, including 606 (51%) positive for HCV antibody and 580 (49%) who were negative. In adjusted analyses, adherence was independently associated with HCV seropositivity [adjusted odds ratio (AOR), 0.48; 95% confidence interval (CI), 0.23-0.97; P = 0.003], higher plasma albumin levels (AOR, 1.07; 95% CI, 1.01-1.12; P = 0.002) and male gender (AOR, 2.53; 95% CI, 1.04-6.15; P = 0.017), but not with injection drug use (IDU), age or other markers of liver injury. There was no evidence of an interaction between HCV and liver injury in adjusted analyses; comparing different strata of HCV and IDU confirmed that HCV was associated with poor adherence independent of IDU. CONCLUSIONS: HCV-coinfected individuals and those with lower albumin are less likely to be adherent to their ART.

Impact of viral load and the duration of primary infection on HIV transmission

Abstract Objectives: HIV 'treatment as prevention' (TasP) describes early treatment of HIV-infected patients intended to reduce viral load and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and of the relation of HIV transmission risk to viral load. Design: A systematic review and meta-analysis. Methods: We searched PubMed and Embase databases for studies that established a relationship between viral load and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analysed assumptions about the relationship between viral load and transmission risk, and between duration of primary infection and transmission risk. Results: We found 36 eligible articles, based on six different study populations. Studies consistently found that larger viral loads lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40. Conclusion: Assumptions and estimates of the relationship between viral load and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account.

Estimating HIV Incidence, Time to Diagnosis, and the Undiagnosed HIV Epidemic Using Routine Surveillance Data.

BACKGROUND Estimates of the size of the undiagnosed HIV-infected population are important to understand the HIV epidemic and to plan interventions, including "test-and-treat" strategies. METHODS We developed a multi-state back-calculation model to estimate HIV incidence, time between infection and diagnosis, and the undiagnosed population by CD4 count strata, using surveillance data on new HIV and AIDS diagnoses. The HIV incidence curve was modelled using cubic splines. The model was tested on simulated data and applied to surveillance data on men who have sex with men in The Netherlands. RESULTS The number of HIV infections could be estimated accurately using simulated data, with most values within the 95% confidence intervals of model predictions. When applying the model to Dutch surveillance data, 15,400 (95% confidence interval [CI] = 15,000, 16,000) men who have sex with men were estimated to have been infected between 1980 and 2011. HIV incidence showed a bimodal distribution, with peaks around 1985 and 2005 and a decline in recent years. Mean time to diagnosis was 6.1 (95% CI = 5.8, 6.4) years between 1984 and 1995 and decreased to 2.6 (2.3, 3.0) years in 2011. By the end of 2011, 11,500 (11,000, 12,000) men who have sex with men in The Netherlands were estimated to be living with HIV, of whom 1,750 (1,450, 2,200) were still undiagnosed. Of the undiagnosed men who have sex with men, 29% (22, 37) were infected for less than 1 year, and 16% (13, 20) for more than 5 years. CONCLUSIONS This multi-state back-calculation model will be useful to estimate HIV incidence, time to diagnosis, and the undiagnosed HIV epidemic based on routine surveillance data.

Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population.

PURPOSE OF REVIEW Improved virological and immunological outcomes and reduced toxicity of antiretroviral combination therapy (ART) raise the hope that life expectancy of HIV-positive persons on ART will approach that of the general population. We systematically review the literature and summarize published estimates of life expectancy of HIV-positive populations on ART. We compare their life expectancy with the life expectancy of the general or, in sub-Saharan Africa, HIV-negative populations, by time period and gender. RECENT FINDINGS Ten relevant studies were published from 2006 to 2015. Three studies were from Canada, two from European countries, three from sub-Saharan Africa and two were multicountry studies. Life expectancy increased over time in all studies and regions. Expressed as the percentage of life expectancy in the HIV-negative or general population, estimated life expectancy at age 20 years in HIV-positive people on ART ranged from 60.3% (95% CI 58.0-62.6%) in Rwanda (2008-2011) to 89.1% (95% CI 84.7-93.6%) in Canada (2008-2012). The percentage of life expectancy in the HIV-negative or general population achieved was higher in HIV-positive women than in HIV-positive men in all countries, except for Canada wherein the opposite was the case. SUMMARY Life expectancy in HIV-positive people on ART has improved worldwide in recent years, but important gaps remain compared with the general and HIV-negative population, and between regions and genders.

Outcomes in patients waiting for antiretroviral treatment in the Free State Province, South Africa: prospective linkage study

Objective: In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pretreatment mortality and access to treatment in patients waiting for ART. Design: Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province. Methods: Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis. Results: Forty-four thousand, eight hundred and forty-four patients enrolled in CHAM between May 2004 and December 2007, of whom 22 083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years [95% confidence interval (CI) 51.8–54.7]. Median CD4 cell count at eligibility increased from 87 cells/ml in 2004 to 101 cells/ml in 2007. Two years after eligibility an estimated 67.7% (67.1–68.4%) of patients had started ART, and 26.2% (25.6–26.9%) died before starting ART. Among patients with CD4 cell counts below 25 cells/ml at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/peri-urban clinics, or better staffed clinics. Conclusions: Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.

Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy

We characterized lipid and lipoprotein changes associated with a lopinavir/ritonavir-containing regimen. We enrolled previously antiretroviral-naive patients participating in the Swiss HIV Cohort Study. Fasting blood samples (baseline) were retrieved retrospectively from stored frozen plasma and posttreatment (follow-up) samples were collected prospectively at two separate visits. Lipids and lipoproteins were analyzed at a single reference laboratory. Sixty-five patients had two posttreatment lipid profile measurements and nine had only one. Most of the measured lipids and lipoprotein plasma concentrations increased on lopinavir/ritonavir-based treatment. The percentage of patients with hypertriglyceridemia (TG >150?mg/dl) increased from 28/74 (38%) at baseline to 37/65 (57%) at the second follow-up. We did not find any correlation between lopinavir plasma levels and the concentration of triglycerides. There was weak evidence of an increase in small dense LDL-apoB during the first year of treatment but not beyond 1 year (odds ratio 4.5, 90% CI 0.7 to 29 and 0.9, 90% CI 0.5 to 1.5, respectively). However, 69% of our patients still had undetectable small dense LDL-apoB levels while on treatment. LDL-cholesterol increased by a mean of 17?mg/dl (90% CI -3 to 37) during the first year of treatment, but mean values remained below the cut-off for therapeutic intervention. Despite an increase in the majority of measured lipids and lipoproteins particularly in the first year after initiation, we could not detect an obvious increase of cardiovascular risk resulting from the observed lipid changes.

A comparison of initial antiretroviral therapy in the Swiss HIV Cohort Study and the recommendations of the International AIDS Society-USA

In order to facilitate and improve the use of antiretroviral therapy (ART), international recommendations are released and updated regularly. We aimed to study if adherence to the recommendations is associated with better treatment outcomes in the Swiss HIV Cohort Study (SHCS).

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE

Background Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. Methods and Findings Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50–500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30–0.40) for counts <200 cells/µl, 0.81 (0.71–0.92) for counts 200 to <350 cells/µl, 0.74 (0.66–0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92–0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. Conclusions Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.

Treatment and prognosis of AIDS-related lymphoma in the era of highly active antiretroviral therapy: findings from the Swiss HIV Cohort Study

OBJECTIVE: To assess the characteristics of combination antiretroviral therapy (cART) administered concomitantly with chemotherapy and to establish prognostic determinants of patients with AIDS-related non-Hodgkin's lymphoma. METHODS: The study included 91 patients with AIDS-related non-Hodgkin's lymphoma from the Swiss HIV Cohort Study enrolled between January 1997 and October 2003, excluding lymphomas of the brain. We extracted AIDS-related non-Hodgkin's lymphoma- and HIV-specific variables at the time of lymphoma diagnosis as well as treatment changes over time from charts and from the Swiss HIV Cohort Study database. Cox regression analyses were performed to study predictors of overall and progression-free survival. RESULTS: During a median follow up of 1.6 years, 57 patients died or progressed. Thirty-five patients stopped chemotherapy prematurely (before the sixth cycle) usually due to disease progression; these patients had a shorter median survival than those who completed six or more cycles (14 versus 28 months). Interruptions of cART decreased from 35% before chemotherapy to 5% during chemotherapy. Factors associated with overall survival were CD4+ T-cell count (<100 cells/microl) (hazard ratio [HR] 2.95 [95% confidence interval (CI) 1.53-5.67], hepatitis C seropositivity (HR 2.39 [95% CI 1.01-5.67]), the international prognostic index score (HR 1.98-3.62 across categories) and Burkitt histological subtypes (HR 2.56 [95% CI 1.13-5.78]). CONCLUSIONS: Interruptions of cART were usually not induced by chemotherapy. The effect of cART interruptions on AIDS-related non-Hodgkin's lymphoma prognosis remains unclear, however, hepatitis C seropositivity emerged-as a predictor of death beyond the well-known international prognostic index score and CD4+ T-cell count.