Dunja Nicca

Outcome of smoking cessation counselling of HIV‐positive persons by HIV care physicians

Smoking is the most prevalent modifiable risk factor for cardiovascular diseases among HIV‐positive persons. We assessed the effect on smoking cessation of training HIV care physicians in counselling.

Adherence as a Predictor of the Development of Class-Specific Resistance Mutations: The Swiss HIV Cohort Study

Background Non-adherence is one of the strongest predictors of therapeutic failure in HIV-positive patients. Virologic failure with subsequent emergence of resistance reduces future treatment options and long-term clinical success. Methods Prospective observational cohort study including patients starting new class of antiretroviral therapy (ART) between 2003 and 2010. Participants were naïve to ART class and completed ≥1 adherence questionnaire prior to resistance testing. Outcomes were development of any IAS-USA, class-specific, or M184V mutations. Associations between adherence and resistance were estimated using logistic regression models stratified by ART class. Results Of 314 included individuals, 162 started NNRTI and 152 a PI/r regimen. Adherence was similar between groups with 85% reporting adherence ≥95%. Number of new mutations increased with increasing non-adherence. In NNRTI group, multivariable models indicated a significant linear association in odds of developing IAS-USA (odds ratio (OR) 1.66, 95% confidence interval (CI): 1.04-2.67) or class-specific (OR 1.65, 95% CI: 1.00-2.70) mutations. Levels of drug resistance were considerably lower in PI/r group and adherence was only significantly associated with M184V mutations (OR 8.38, 95% CI: 1.26-55.70). Adherence was significantly associated with HIV RNA in PI/r but not NNRTI regimens. Conclusion Therapies containing PI/r appear more forgiving to incomplete adherence compared with NNRTI regimens, which allow higher levels of resistance, even with adherence above 95%. However, in failing PI/r regimens good adherence may prevent accumulation of further resistance mutations and therefore help to preserve future drug options. In contrast, adherence levels have little impact on NNRTI treatments once the first mutations have emerged.

Self-reported nonadherence to antiretroviral therapy as a predictor of viral failure and mortality

Objective:To determine the effect of nonadherence to antiretroviral therapy (ART) on virologic failure and mortality in naive individuals starting ART. Design:Prospective observational cohort study. Methods:Eligible individuals enrolled in the Swiss HIV Cohort Study, started ART between 2003 and 2012, and provided adherence data on at least one biannual clinical visit. Adherence was defined as missed doses (none, one, two, or more than two) and percentage adherence (>95, 90–95, and <90) in the previous 4 weeks. Inverse probability weighting of marginal structural models was used to estimate the effect of nonadherence on viral failure (HIV-1 viral load >500 copies/ml) and mortality. Results:Of 3150 individuals followed for a median 4.7 years, 480 (15.2%) experienced viral failure and 104 (3.3%) died, 1155 (36.6%) reported missing one dose, 414 (13.1%) two doses and, 333 (10.6%) more than two doses of ART. The risk of viral failure increased with each missed dose (one dose: hazard ratio [HR] 1.15, 95% confidence interval 0.79–1.67; two doses: 2.15, 1.31–3.53; more than two doses: 5.21, 2.96–9.18). The risk of death increased with more than two missed doses (HR 4.87, 2.21–10.73). Missing one to two doses of ART increased the risk of viral failure in those starting once-daily (HR 1.67, 1.11–2.50) compared with those starting twice-daily regimens (HR 0.99, 0.64–1.54, interaction P = 0.09). Consistent results were found for percentage adherence. Conclusion:Self-report of two or more missed doses of ART is associated with an increased risk of both viral failure and death. A simple adherence question helps identify patients at risk for negative clinical outcomes and offers opportunities for intervention.

Outcomes of Antiretroviral Therapy in the Swiss HIV Cohort Study: Latent Class Analysis

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions.

Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Background Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels. Methods Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period. Results From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56). Conclusions The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.

The Advanced Nursing Practice Team as a Model for HIV/AIDS Caregiving in Switzerland

To offer advanced nursing care for people living with HIV, a participatory action research project was initiated that enabled constant learning and change at the levels of (a) the culture and organization of an outpatient department, (b) clinical leadership and interdisciplinary collaboration, and (c) development of new services. In this project, the development of the Advanced Nursing Practice (ANP) Team not only affected the practice of individual nurses with advanced degrees but also created a team of nurses educated at different levels. Through a systematic process, the nurses on the team became more educated and refined their clinical expertise. An essential aspect of the ANP Team was the specialization of each nurse in a self-selected topic within HIV/AIDS care. As members of the ANP Team, the nurses offer state-of-the-art nursing care including patient assessment, medication management and adherence support, symptom management, health maintenance and prevention, and family support for persons living with HIV.

Incidence of hepatitis C in HIV positive and negative men who have sex with men 2000–2016: a systematic review and meta-analysis

BackgroundThere is a need for systematic reviews and meta-analyses to synthesize the epidemiology, and the riskfactors for hepatitis C virus (HCV) among HIV-coinfected and HIV negative men who have sex with men (MSM).MethodsA meta-analysis of 28 studies was carried out by pooling HCV incidence data of HIV-coinfected and HIV negative MSM. Differences in incidence outcome depending on the prospective or retrospective nature of the individual studies were investigated.ResultsThe pooled incidence of HCV in MSM was 6.3 per 1000 person-years (95% CI 5.0–7.5). The overall estimated incidence was 19-fold higher in HIV positive compared to HIV negative MSM living in resource-rich countries. This result was confirmed when the analysis was restricted to high-quality studies. Factors associated with an increased risk for incident HCV included behavioural factors (sexual risk behaviour and recreational drug use) as well as biological characteristics (HIV coinfection and a recent history of syphilis).ConclusionIn conclusion, incident HCV predominantly affects HIV positive MSM. The incidence rate varied largely between studies, factors such as study design might play an important role.

Population pharmacokinetic analysis of elvitegravir and cobicistat in HIV-1-infected individuals

OBJECTIVES Co-formulated elvitegravir, cobicistat, tenofovir disoproxil fumarate and emtricitabine is among the preferred regimens for first-line ART. A population approach was used to characterize the pharmacokinetics of elvitegravir and cobicistat and identify individual factors and co-medications influencing their disposition, taking into consideration the interaction between the two compounds. METHODS The study population included 144 HIV-infected individuals who provided 186 and 167 elvitegravir and cobicistat plasma concentrations, respectively. First, distinct NONMEM(®) analyses were conducted for elvitegravir and cobicistat, including individual demographic, clinical and genetic factors as potential covariates. Elvitegravir and cobicistat interaction was then assessed through different inhibitory models. Simulations based on the final model served to compare expected drug concentrations under standard and alternative dosage regimens. RESULTS Clearance with between-subject variability was 7.6 L/h [coefficient of variation (CV) 16.6%] and volume of distribution 61 L for elvitegravir and 16.0 L/h (CV 41.9%) and 88.3 L, respectively, for cobicistat. Concomitant administration of non-ritonavir-boosted atazanavir decreased elvitegravir clearance by 35%, likely due to UDP-glucuronosyl transferase (UGT) 1A1 inhibition. Concomitant administration of non-ritonavir-boosted atazanavir and ritonavir-boosted darunavir decreased cobicistat clearance by 47% and 27%, respectively. The final interaction model included cobicistat exposure (AUC0-24) on elvitegravir clearance. Simulations confirmed that a reduced elvitegravir dose of 85 mg co-administered with cobicistat and atazanavir produces a concentration-time course comparable to the standard regimen without atazanavir. CONCLUSIONS Elvitegravir and cobicistat pharmacokinetic variability appears to be mainly explained by drug-drug interactions that may be encountered in routine clinical practice. In these cases, therapeutic drug monitoring and surveillance for potential toxicities would be justified.

Predicting smoking cessation and its relapse in HIV-infected patients: the Swiss HIV Cohort Study

The aim of the study was to assess whether prospective follow‐up data within the Swiss HIV Cohort Study can be used to predict patients who stop smoking; or among smokers who stop, those who start smoking again.

Symptom Management in HIV/AIDS: A Mixed Methods Approach to Describe Collaboration and Concordance Between Persons Living With HIV and Their Close Support Persons

For persons living with HIV, effective symptom management is crucial for good health outcomes and usually involves close support persons. The collaboration of persons living with HIV and their close support persons in the process of symptom management, including symptom experience reports, was investigated using an exploratory mixed methods design. Integration of methods included hypothesis generation from participants’ narratives. Results revealed that collaboration is constituted by distinct but integrative positions of manager and partner that are reflected in diverse themes of symptom management and confirmed in quantitatively assessed symptom reports. Divergent qualitative and quantitative findings highlighted problems in neurocognitive symptom communication. Symptom management processes should be supported by better integrating the close support persons into clinical service, and further research on neurocognitive symptom experience is needed.