Objectives
Understanding the drivers of HIV‐1 transmission is of importance for curbing the ongoing epidemic. Phylogenetic methods based on single viral sequences allow us to assess whether two ...individuals are part of the same viral outbreak, but cannot on their own assess who potentially transmitted the virus. We developed and assessed a molecular epidemiology method with the main aim to screen cohort studies for and to characterize individuals who are ‘potential HIV‐1 transmitters’, in order to understand the drivers of HIV‐1 transmission.
Methods
We developed and validated a molecular epidemiology approach using longitudinally sampled viral Sanger sequences to characterize potential HIV‐1 transmitters in the Swiss HIV Cohort Study.
Results
Our method was able to identify 279 potential HIV‐1 transmitters and allowed us to determine the main epidemiological and virological drivers of transmission. We found that the directionality of transmission was consistent with infection times for 72.9% of 85 potential HIV‐1 transmissions with accurate infection date estimates. Being a potential HIV‐1 transmitter was associated with risk factors including viral load adjusted odds ratiomultivariable (95% confidence interval): 1.86 (1.49–2.32), syphilis coinfection 1.52 (1.06–2.19), and recreational drug use 1.45 (1.06–1.98). By contrast for the potential HIV‐1 recipients, this association was weaker or even absent 1.18 (0.82–1.72), 0.89 (0.52–1.55) and 1.53 (0.98–2.39), respectively, indicating that inferred directionality of transmission is useful at the population level.
Conclusions
Our results indicate that longitudinally sampled Sanger sequences do not provide sufficient information to identify transmitters with high certainty at the individual level, but that they allow the drivers of transmission at the population level to be characterized.
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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
Tenofovir alafenamide (TAF)-containing combinations were introduced in Switzerland after October 2016 and are recommended over tenofovir disoproxil fumarate (TDF) in patients with osteoporosis or ...impaired renal function. We included all participants of the Swiss HIV Cohort Study on TDF-containing antiretroviral therapy with follow-up visits after January 2016. We determined the proportion of switches from TDF to TAF overall, and among patients with risk factors for TDF toxicity, including osteoporosis, impaired renal function or marked proteinuria. We used multivariable logistic regression to explore predictors of switching from TDF to TAF. We included 5'012 patients, of whom 652 (13.0%) had risk factors for TDF toxicity. A switch from TDF to TAF was undertaken in 2'796 (55.8%) individuals overall, and in 465 (71.3%) with risk factors. Predictors of switching to TAF were male sex (adjusted odds ratio 1.27, 95% confidence interval 1.07-1.50), age > 50 years (1.43, 1.23-1.66) and the presence of risk factors for TDF toxicity (2.21, 1.77-2.75). In contrast, patients with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-pill regimen (0.11, 0.09-0.13), those treated in non-tertiary care centers (0.56, 0.46-0.70), as well as those with CD4 cell counts below 500/muL (0.77, 0.66-0.90) and with chronic hepatitis C infection (0.66, 0.54-0.80) were most likely to stay on TDF. Over 50% of patients on TDF-containing therapy, including the majority of patients at risk for TDF toxicity, were switched to TAF within two years of its introduction in Switzerland. Individuals on NNRTI-based single-pill regimens were most likely to remain on TDF.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Despite the huge success of antiretroviral therapy (ART), there is an ongoing HIV epidemic among men who have sex with men (MSM) in resource‐rich countries. Understanding the driving ...factors underlying this process is important for curbing the epidemic.
Methods
We simulated the HIV epidemic in MSM in Switzerland by stratifying a mathematical model by CD4 count, the care cascade and condom use. The model was parametrised with clinical, epidemiological and behavioural data from the Swiss HIV Cohort Study and surveys in the HIV‐negative population.
Results
According to our model, 3.4% of the cases that would otherwise have occurred in 2008–2015 were prevented by early initiation of ART. Only 0.6% of the cases were attributable to a change in condom use in the HIV‐positive population, as less usage is mainly seen in virally suppressed MSM. Most new infections were attributable to transmission from recently infected undiagnosed individuals. It was estimated that doubling the diagnosis rate would have resulted in 11.8% fewer cases in 2001–2015. Moreover, it was estimated that introducing pre‐exposure prophylaxis (PrEP) for 50% of those MSM not using condoms with occasional partners would have resulted in 22.6% fewer cases in 2012–2015.
Conclusions
By combining observational data on the relevant epidemiological and clinical processes with a mathematical model, we showed that the ‘test and treat’ approach is most effective in reducing the number of new cases. Only a moderate population‐level effect was estimated for early initiation of ART and a weak effect for the change in condom use of diagnosed MSM. Protecting HIV‐negative individuals who are not using condoms with PrEP was shown to have a major impact.
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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
To assess the impact of primary HIV infection (PHI) on the spread of HIV and the temporal trends in transmission of HIV drug resistance between 1996 and 1999 in Switzerland.
Sequencing of the genes ...for reverse transcriptase (RT) and protease was performed for 197 individuals with documented PHI. Phylogenetic analyses were confronted with epidemiological data.
Significant clustering was demonstrated for 29% of the RT sequences. All these cases occurred closely together in place and time; contact tracing demonstrated transmission at the time of PHI in 30% of them. Genotypic drug resistance was detected in 8.6% of PHI individuals in 1996, 14.6% in 1997, 8.8% in 1998 and 5.0% in 1999. Drug-resistant variants were identified in 11.3% of individuals infected by homosexual contacts, 6.1% by heterosexual contacts, 13% of intravenous drug users and more frequently in men (10.4%) than women (2.6%). Potential factors involved in the recent decrease of transmission of drug-resistant variants include increase of HIV non-B subtypes from 23% in 1996 to 35% in 1999 (only one non-B subtype had resistance mutations) and a steady increase of patients with undetectable viraemia as documented in Swiss HIV Cohort Study (10% in 1996 vs 53% in 1999).
Phylogenetic and epidemiological analyses underline the impact of PHI in the spread of HIV. Moreover, this study indicates that drug resistance transmission may have decreased recently in Switzerland through the increased frequency of infection with HIV non-B subtypes and the steady increase of patients with undetectable viraemia.
Abstract
Background
Incomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, ...its clinical implications remain unknown.
Methods
PWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression (<50 copies/mL) for ≥6 months were evaluated. The association between incomplete self-reported ART adherence (≥1 or ≥2 missed doses in the last month) and (1) any CVD event (myocardial infarction, revascularization, cerebral hemorrhage, stroke, and/or death due to CVD event) or (2) non-CVD-related death was evaluated using adjusted Cox proportional hazards models.
Results
A total of 6971 PWH (74% male) were included in the analysis (median age interquartile range {IQR}, 39 32–47 years). The median (IQR) follow-up was 8 (4–11) years, with 14 (8–23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing ≥1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio HR, 1.23; 95% CI, 0.85–1.79; P = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing ≥1 ART dose (HR, 1.44; 95% CI, 1.00–2.07; P = .05) and missing ≥2 ART doses (HR, 2.21; 95% CI, 1.37–3.57; P = .001).
Conclusions
Incomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes.
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.
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