Objectives
Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level ...trajectories differ between patients with treatment‐induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV‐infected MSM with different clinical outcomes.
Methods
We investigated anti‐HCV antibody level dynamics following an incident HCV infection in 67 HIV‐infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter.
Results
At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut‐off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow‐up, SVR was associated with a more pronounced decrease in anti‐HCV levels compared with spontaneous clearance and untreated infection median decline 71% interquartile range (IQR: 43–87%), 38% (IQR: 29–60%) and 12% (IQR: 9–22%), respectively; P < 0.001. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection.
Conclusions
Treatment‐induced HCV clearance was associated with a more pronounced decline in anti‐HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV‐infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Management of persistent low-level viraemia (pLLV) in patients on combined antiretroviral therapy (cART) with previously undetectable HIV viral loads (VLs) is challenging. We examined virological ...outcome and management among patients enrolled in the Swiss HIV Cohort Study (SHCS).
In this retrospective study (2000-2011), pLLV was defined as a VL of 21-400 copies/ml on ≥ three consecutive plasma samples with ≥8 weeks between first and last analyses, in patients undetectable for ≥24 weeks on cART. Control patients had ≥ three consecutive undetectable VLs over ≥32 weeks. Virological failure (VF), analysed in the pLLV patient group, was defined as a VL>400 copies/ml.
Among 9,972 patients, 179 had pLLV and 5,389 were controls. Compared to controls, pLLV patients were more often on unboosted protease inhibitor (PI)-based (adjusted odds ratio aOR; 95% CI 3.2 1.8, 5.9) and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)-only combinations (aOR 2.1 1.1, 4.2) than on non-nucleoside reverse transcriptase inhibitor and boosted PI-based regimens. At 48 weeks, 102/155 pLLV patients (66%) still had pLLV, 19/155 (12%) developed VF and 34/155 (22%) had undetectable VLs. Predictors of VF were previous VF (aOR 35 3.8, 315), unboosted PI-based (aOR 12.8 1.7, 96) or NRTI-only combinations (aOR 115 6.8, 1,952), and VLs>200 during pLLV (aOR 3.7 1.1, 12). No VF occurred in patients with persistent very LLV (21-49 copies/ml; n=26). At 48 weeks, 29/39 patients (74%) who changed cART had undetectable VLs, compared with 19/74 (26%) without change (P<0.001).
Among patients with pLLV, VF was predicted by previous VF, cART regimen and VL≥200. Most patients who changed cART had undetectable VLs 48 weeks later. These findings support cART modification for pLLV>200 copies/ml.
Objectives
Women with HIV infection are mainly of reproductive age and need safe, effective and affordable contraception to avoid unintended pregnancies. The aim of this study was to evaluate ...contraceptive use and unintended pregnancies in this population in Switzerland.
Methods
A self‐report anonymous questionnaire on contraceptive methods, adherence to them, and unintended pregnancies was completed by women included in the Swiss HIV Cohort Study (SHCS) between November 2013 and June 2014. Sociodemographic characteristics and information related to combined antiretroviral therapy and HIV disease status were obtained from the SHCS database.
Results
Of 462 women included, 164 (35.5%) reported not using any contraception. Among these, 65 (39.6%) reported being sexually active, although 29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the following methods were reported: condoms, 219 (73.5%); oral hormonal contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women on contraception, 32 (10.7%) reported using more than one contraceptive method and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16, oral contraception; four, other methods). Of these, 68.1% terminated the pregnancy and almost half (43.7%) continued using the same contraceptive method after the event.
Conclusions
Family planning needs in HIV‐positive women are not fully addressed because male condoms remained the predominant reported contraceptive method, with a high rate of unintended pregnancies. It is of utmost importance to provide effective contraception such as long‐acting reversible contraceptives for women living with HIV.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Syphilis is re-emerging globally in general and HIV-infected populations, and repeated syphilis episodes may play a central role in syphilis transmission among core groups. Besides sexual behavioral ...factors, little is known about determinants of repeated syphilis episodes in HIV-infected individuals-including the potential impact of preceding syphilis episodes on subsequent syphilis risk.
In the prospective Swiss HIV cohort study, with routine syphilis testing since 2004, we analyzed HIV-infected men who have sex with men (MSM). Our primary outcome was first and repeated syphilis episodes. We used univariable and multivariable Andersen-Gill models to evaluate risk factors for first and repeated incident syphilis episodes.
Within the 14-year observation period, we included 2513 HIV-infected MSM with an initially negative syphilis test. In the univariable and multivariable analysis, the number of prior syphilis episodes (adjusted hazard ratio aHR per 1-episode increase, 1.15; 95% confidence interval CI, 1.01-1.31), having occasional sexual partners with or without condomless anal sex (aHR, 4.99; 95% CI, 4.08-6.11; and aHR, 2.54; 95% CI, 2.10-3.07), and being currently on antiretroviral therapy (aHR, 1.62; 95% CI, 1.21-2.16) were associated with incident syphilis.
In HIV-infected MSM, we observed no indication of decreased syphilis risk with repeated syphilis episodes. The extent of sexual risk behavior over time was the strongest risk factor for repeated syphilis episodes. The observed association of antiretroviral therapy with repeated syphilis episodes warrants further immunological and epidemiological investigation.
Increasing obesity rates in Swiss HIV+ persons may partially be due to aging, demographic changes and earlier ART start. Most BMI increase occurred in year 1 of ART. The effect of individual ART ...regimens was limited.
Background.
The factors that contribute to increasing obesity rates in human immunodeficiency virus (HIV)-positive persons and to body mass index (BMI) increase that typically occurs after starting antiretroviral therapy (ART) are incompletely characterized.
Methods.
We describe BMI trends in the entire Swiss HIV Cohort Study (SHCS) population and investigate the effects of demographics, HIV-related factors, and ART on BMI change in participants with data available before and 4 years after first starting ART.
Results.
In the SHCS, overweight/obesity prevalence increased from 13% in 1990 (n = 1641) to 38% in 2012 (n = 8150). In the participants starting ART (n = 1601), mean BMI increase was 0.92 kg/m2 per year (95% confidence interval, .83–1.0) during year 0–1 and 0.31 kg/m2 per year (0.29–0.34) during years 1–4. In multivariable analyses, annualized BMI change during year 0–1 was associated with older age (0.15 0.06–0.24 kg/m2) and CD4 nadir <199 cells/µL compared to nadir >350 (P < .001). Annualized BMI change during years 1–4 was associated with CD4 nadir <100 cells/µL compared to nadir >350 (P = .001) and black compared to white ethnicity (0.28 0.16–0.37 kg/m2). Individual ART combinations differed little in their contribution to BMI change.
Conclusions.
Increasing obesity rates in the SHCS over time occurred at the same time as aging of the SHCS population, demographic changes, earlier ART start, and increasingly widespread ART coverage. Body mass index increase after ART start was typically biphasic, the BMI increase in year 0–1 being as large as the increase in years 1–4 combined. The effect of ART regimen on BMI change was limited.
There is limited data on abdominal obesity and the influence of genetics on weight change after antiretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) ...change over time in the Swiss HIV Cohort study (SHCS).
Mixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background.
Individuals with CD4 nadir <100 cells/µL gained 6.4 times more BMI than individuals with ≥200, and 2.8 times more WHR than individuals with ≥100 (
< .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir <100 cells/µL compared to 100-199 (odds ratio OR, 2.07; 95% confidence interval CI, 1.63-2.74) and ≥200 (OR, 1.69; 95% CI, 1.26-2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir <100 compared to ≥100 (OR, 1.35; 95% CI, 1.17-1.54 in men; OR, 1.36; 95% CI, 1.18-1.57 in women), persisting after 10 years of ART. No significant differences were found across antiretroviral drug classes or genetic scores.
The risk of general and abdominal obesity increased with CD4 nadir <100 cells/µL. Based on our results, including the genetic background would not improve obesity predictions in HIV-infected individuals.
Objectives
A significant percentage of patients infected with HIV‐1 experience only suboptimal CD4 cell recovery while treated with combination therapy (cART). It is still unclear whether viral ...properties such as cell tropism play a major role in this incomplete immune response. This study therefore intended to follow the tropism evolution of the HIV‐1 envelope during periods of suppressive cART.
Methods
Viruses from two distinct patient groups, one with good and another one with poor CD4 recovery after 5 years of suppressive cART, were genotypically analysed for viral tropism at baseline and at the end of the study period.
Results
Patients with CCR5‐tropic CC‐motif chemokine receptor 5 viruses at baseline tended to maintain this tropism to the study end. Patients who had a CXCR4‐tropic CXC‐motif chemokine receptor 4 virus at baseline were overrepresented in the poor CD4 recovery group. Overall, however, the majority of patients presented with CCR5‐tropic viruses at follow‐up.
Conclusions
Our data lend support to the hypothesis that tropism determination can be used as a parameter for disease progression even if analysed long before the establishment of a poorer immune response. Moreover, the lasting predominating CCR5‐tropism during periods of full viral control suggests the involvement of cellular mechanisms that preferentially reduce CXCR4‐tropic viruses during cART.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In the Swiss HIV Cohort Study, the number of people who inject drugs with replicating hepatitis C virus (HCV) infection decreased substantially after the introduction of direct-acting antivirals ...(DAAs). Among men who have sex with men, the increase in DAA uptake and efficacy was counterbalanced by frequent incident HCV infections.
Age-mixing patterns are of key importance for understanding the dynamics of human immunodeficiency virus (HIV)-epidemics and target public health interventions. We use the densely sampled Swiss HIV ...Cohort Study (SHCS) resistance database to study the age difference at infection in HIV transmission pairs using phylogenetic methods. In addition, we investigate whether the mean age difference of pairs in the phylogenetic tree is influenced by sampling as well as by additional distance thresholds for including pairs. HIV-1
-sequences of 11,922 SHCS patients and approximately 240,000 Los Alamos background sequences were used to build a phylogenetic tree. Using this tree, 100 per cent down to 1 per cent of the tips were sampled repeatedly to generate pruned trees (
= 500 for each sample proportion), of which pairs of SHCS patients were extracted. The mean of the absolute age differences of the pairs, measured as the absolute difference of the birth years, was analyzed with respect to this sample proportion and a distance criterion for inclusion of the pairs. In addition, the transmission groups men having sex with men (MSM), intravenous drug users (IDU), and heterosexuals (HET) were analyzed separately. Considering the tree with all 11,922 SHCS patients, 2,991 pairs could be extracted, with 954 (31.9 per cent) MSM-pairs, 635 (21.2 per cent) HET-pairs, 414 (13.8 per cent) IDU-pairs, and 352 (11.8 per cent) HET/IDU-pairs. For all transmission groups, the age difference at infection was significantly (P < 0.001) smaller for pairs in the tree compared with randomly assigned pairs, meaning that patients of similar age are more likely to be pairs. The mean age difference in the phylogenetic analysis, using a fixed distance of 0.05, was 9.2, 9.0, 7.3 and 5.6 years for MSM-, HET-, HET/IDU-, and IDU-pairs, respectively. Decreasing the cophenetic distance threshold from 0.05 to 0.01 significantly decreased the mean age difference. Similarly, repeated sampling of 100 per cent down to 1 per cent of the tips revealed an increased age difference at lower sample proportions. HIV-transmission is age-assortative, but the age difference of transmission pairs detected by phylogenetic analyses depends on both sampling proportion and distance criterion. The mean age difference decreases when using more conservative distance thresholds, implying an underestimation of age-assortativity when using liberal distance criteria. Similarly, overestimation of the mean age difference occurs for pairs from sparsely sampled trees, as it is often the case in sub-Saharan Africa.
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