To compare the frequency and risk factors of toxicity-related treatment discontinuations between raltegravir and dolutegravir.
Prospective cohort study.
All antiretroviral therapy (ART)-naïve and ...ART-experienced HIV-infected individuals from the Swiss HIV Cohort Study who initiated raltegravir or dolutegravir between 2006 and 2015 were investigated concerning treatment modification within the first year.
Of 4041 patients initiating ART containing raltegravir (n = 2091) or dolutegravir (n = 1950), 568 patients discontinued ART during the first year, corresponding to a rate of 15.5 95% confidence interval (CI) 14.5-16.9 discontinuations per 100 patient-years. Only 10 patients on raltegravir (0.5%) and two patients on dolutegravir (0.1%) demonstrated virologic failure. The main reason for ART discontinuation was convenience expressed as patient's wish, physician's decision, or treatment simplification (n = 302). Toxicity occurred in 4.3% of patients treated with raltegravir and 3.6% with dolutegravir, respectively. In multivariable analysis, the only independent risk factor for discontinuing ART because of toxicity was female sex (hazard ratio 1.98, 95% CI 1.45-2.71, P < 0.001).Neuropsychiatric complaints were the most commonly reported toxic adverse events and more frequent in the dolutegravir (n = 33, 1.7%) compared with the raltegravir group (n = 13, 0.6%). Risk of discontinuation for neurotoxicity was lower for raltegravir than for dolutegravir in multivariable analysis (hazard ratio 0.46, 95% CI 0.22-0.96, P = 0.037).
In this, large cohort raltegravir and dolutegravir-containing regimen demonstrated a high virologic efficacy. Drug toxicity was infrequent and discontinuation because of neuropsychiatric events within the first year of treatment was only marginal higher with dolutegravir compared with raltegravir. However, monitoring of neurotoxic side-effects of dolutegravir is important.
To analyse mortality, loss to follow-up (LTFU) and retention on antiretroviral treatment (ART) in the first year of ART across all age groups in the Malawi national ART programme.
Cohort study ...including all patients who started ART in Malawi's public sector clinics between 2004 and 2007.
ART registers were photographed, information entered into a database and merged with data from clinics with electronic records. Rates per 100 patient-years and cumulative incidence of retention were calculated. Subhazard ratios (sHRs) of outcomes adjusted for patient and clinic-level characteristics were calculated in multivariable analysis, applying competing risk models.
A total of 117,945 patients contributed 85,246 person-years: 1.0% were infants below 2 years, 7.4% children 2-14, 7.5% young people 15-24, and 84.2% adults 25 years and above. Sixty percent of patients were female: women outnumbered men from age 14 to 35 years. Mortality and LTFU were higher in men from age 20 years. Infants and young people had the highest rates per 100 person-years for mortality (23.0 and 19.4) and LTFU (24.7 and 19.3), and the highest adjusted relative risks compared to age group 25-34 years: sHRs were 1.37 95% confidence interval (CI) 1.17-1.60 and 1.17 (95% CI 1.10-1.25) for death and 1.37 (95% CI 1.18-1.59) and 1.27 (95% CI 1.19-1.35) for LTFU, respectively.
In this country-wide study patients aged 0-1 and 15-24 years had the highest risk of death and LTFU, and from age 20 men were at higher risk than women. Interventions to improve outcomes in these patient groups are required.
To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts.
We included ...18,706 adult patients starting ART in South Africa and 80,937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months.
In South Africa, 9.8% 95% confidence interval (CI) 9.1-10.5 had switched at 3 years, 1.3% (95% CI 0.9-1.6) remained on failing first-line regimens, 9.2% (95% CI 8.5-9.8) were lost to follow-up and 4.3% (95% CI 3.9-4.8) had died. In Malawi and Zambia, more patients were on a failing first-line regimen 3.7% (95% CI 3.6-3.9, fewer patients had switched 2.1% (95% CI 2.0-2.3) and more patients were lost to follow-up 15.3% (95% CI 15.0-15.6) or had died 6.3% (95% CI 6.0-6.5). Median CD4 cell counts were lower in South Africa at the start of ART (93 vs. 132 cells/μl; P < 0.001) but higher after 3 years (425 vs. 383 cells/μl; P < 0.001). The hazard ratio comparing South Africa with Malawi and Zambia after adjusting for age, sex, first-line regimen and CD4 cell count was 0.58 (0.50-0.66) for death and 0.53 (0.48-0.58) for loss to follow-up.
Over 3 years of ART mortality was lower in South Africa than in Malawi or Zambia. The more favourable outcome in South Africa might be explained by viral load monitoring leading to earlier detection of treatment failure, adherence counselling and timelier switching to second-line ART.
ObjectiveSeverity of the COVID-19 has been previously reported in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general ...population is presented.DesignRetrospective population-based study.SettingIndividual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared with the all-cause mortality in the Swiss population of 2018. Starting 23 February 2020, mortality in COVID-19 patients was monitored for 80 days and compared with the population mortality observed in the same time of year starting 23 February 2018.Participants5 102 300 inhabitants of Switzerland aged 35–95 without COVID-19 (general population in spring 2018) and 20 769 persons tested positively for COVID-19 during the first wave in spring 2020.MeasurementsSex-specific and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex-specific and age-specific absolute mortality in COVID-19 patients and the corresponding mortality in the 2018 general population.ResultsAbsolute mortalities increased with age and were higher for males compared with females, both in the general population and in positively tested persons. A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups at least eightfold. The highest relative mortality risks were observed among males and younger patients. Male COVID-19 patients exceeded the population hazard for males (HR 1.21, 95% CI 1.02 to 1.44). An additional year of age increased the population hazard in COVID-19 patients only marginally (HR 1.00, 95% CI 1.00 to 1.01).ConclusionsHealthcare professionals, decision-makers and societies are provided with an additional population-adjusted assessment of COVID-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of COVID-19.
ObjectiveDuring the first COVID-19 wave in Switzerland, relative mortality was at least eight times higher compared with the uninfected general population. We aimed to assess sex-specific and ...age-specific relative mortality associated with a SARS-CoV-2 diagnosis during the second wave.DesignProspective population-based study.SettingIndividuals testing positive for SARS-CoV-2 after the start of the second wave on 1 October 2020 were followed up until death or administrative censoring on 31 December 2020.Participants5 179 740 inhabitants of Switzerland in fall 2018 aged 35–95 years (without COVID-19) and 257 288 persons tested positive for SARS-CoV-2 by PCR or antigen testing during the second wave.Primary and secondary outcome measuresThe planned outcome measure was time to death from any cause, measured from the date of a SARS-CoV-2 diagnosis or 1 October in the general population. Information on confirmed SARS-CoV-2 diagnoses and deaths was matched by calendar time with the all-cause mortality of the general Swiss population of 2018. Proportional hazards models were used to estimate sex-specific and age-specific mortality rates and probabilities of death within 60 days.ResultsThe risk of death for individuals tested positive for SARS-CoV-2 in the second wave in Switzerland increased at least sixfold compared with the general population. HRs, reflecting the risk attributable to a SARS-CoV-2 infection, were higher for men (1.40, 95% CI 1.29 to 1.52) and increased for each additional year of age (1.01, 95% CI 1.01 to 1.02). COVID-19 mortality was reduced by at least 20% compared with the first wave in spring 2020.ConclusionGeneral mortality patterns, increased for men and older persons, were similar in spring and in fall. Absolute and relative COVID-19 mortality was smaller in fall.Trial registrationThe protocol for this study was registered on 3 December 2020 at https://osf.io/gbd6r.
Few data are available on the long-term immunologic response to antiretroviral therapy (ART) in resource-limited settings, where ART is being rapidly scaled up using a public health approach, with a ...limited repertoire of drugs.
To describe immunologic response to ART among ART patients in a network of cohorts from sub-Saharan Africa, Latin America, and Asia. STUDY POPULATION/METHODS: Treatment-naive patients aged 15 and older from 27 treatment programs were eligible. Multilevel, linear mixed models were used to assess associations between predictor variables and CD4 cell count trajectories following ART initiation.
Of 29 175 patients initiating ART, 8933 (31%) were excluded due to insufficient follow-up time and early lost to follow-up or death. The remaining 19 967 patients contributed 39 200 person-years on ART and 71 067 CD4 cell count measurements. The median baseline CD4 cell count was 114 cells/microl, with 35% having less than 100 cells/microl. Substantial intersite variation in baseline CD4 cell count was observed (range 61-181 cells/microl). Women had higher median baseline CD4 cell counts than men (121 vs. 104 cells/microl). The median CD4 cell count increased from 114 cells/microl at ART initiation to 230 interquartile range (IQR) 144-338 at 6 months, 263 (IQR 175-376) at 1 year, 336 (IQR 224-472) at 2 years, 372 (IQR 242-537) at 3 years, 377 (IQR 221-561) at 4 years, and 395 (IQR 240-592) at 5 years. In multivariable models, baseline CD4 cell count was the most important determinant of subsequent CD4 cell count trajectories.
These data demonstrate robust and sustained CD4 response to ART among patients remaining on therapy. Public health and programmatic interventions leading to earlier HIV diagnosis and initiation of ART could substantially improve patient outcomes in resource-limited settings.
In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available ...in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.
Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models.
A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months interquartile range (IQR) 10.1-26.6 in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79).
In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.
Abstract
Background
Integrase strand transfer inhibitors (INSTIs) have been associated with an increased risk for cardiovascular disease (CVD) events. We investigated the impact of starting ...INSTI-based antiretroviral therapy (ART) on CVD events among treatment-naïve people with human immunodeficiency virus using a target trial framework, which reduces the potential for confounding and selection bias.
Methods
We included Swiss HIV Cohort Study participants who were ART-naïve after May 2008, when INSTIs became available in Switzerland. Individuals were categorized according to their first ART regimen (INSTI vs other ART) and were followed from ART start until the first of CVD event (myocardial infarction, stroke, or invasive cardiovascular procedure), loss to follow-up, death, or last cohort visit. We calculated hazard ratios and risk differences using pooled logistic regression models with inverse probability of treatment and censoring weights.
Results
Of 5362 participants (median age 38 years, 21% women, 15% of African origin), 1837 (34.3%) started INSTI-based ART, and 3525 (65.7%) started other ART. Within 4.9 years (interquartile range, 2.4–7.4), 116 CVD events occurred. Starting INSTI-based ART was not associated with an increased risk for CVD events (adjusted hazard ratio, 0.80; 95% confidence interval CI, .46–1.39). Adjusted risk differences between individuals who started INSTIs and those who started other ART were −0.17% (95% CI, −.37 to .19) after 1 year, −0.61% (−1.54 to 0.22) after 5 years, and −0.71% (−2.16 to 0.94) after 8 years.
Conclusions
In this target trial emulation, we found no difference in short- or long-term risk for CVD events between treatment-naïve people with human immunodeficiency virus who started INSTI-based ART and those on other ART.
In treatment-naïve people with HIV, starting antiretroviral therapy containing integrase strand transfer inhibitors did not lead to an increased risk for cardiovascular disease events in this target trial emulation from the Swiss HIV Cohort Study.
Graphical Abstract
Graphical Abstract
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/impact-of-integrase-inhibitors-on-cardiovascular-disease-events-in-people-with-hiv-starting-antiretroviral-therapy-2cc8a06e-dbe6-4aea-a856-cef20beefd00
Abstract
Background
The extent of inappropriate prescribing observed in geriatric medicine has not been thoroughly evaluated in people ageing with HIV. We determined the prevalence of and risk ...factors for inappropriate prescribing in individuals aged ≥75 years enrolled in the Swiss HIV Cohort Study.
Methods
Retrospective review of medical records was performed to gain more insights into non-HIV comorbidities. Inappropriate prescribing was screened using the Beers criteria, the STOPP/START criteria and the Liverpool drug–drug interactions (DDIs) database.
Results
For 175 included individuals, the median age was 78 years (IQR 76–81) and 71% were male. The median number of non-HIV comorbidities was 7 (IQR 5–10). The prevalence of polypharmacy and inappropriate prescribing was 66% and 67%, respectively. Overall, 40% of prescribing issues could have deleterious consequences. Prescribing issues occurred mainly with non-HIV drugs and included: incorrect dosage (26%); lack of indication (21%); prescription omission (drug not prescribed although indicated) (17%); drug not appropriate in elderly individuals (18%) and deleterious DDIs (17%). In the multivariable logistic regression, risk factors for prescribing issues were polypharmacy (OR: 2.5; 95% CI: 1.3–4.7), renal impairment (OR: 2.7; 95% CI: 1.4–5.1), treatment with CNS-active drugs (OR: 2.1; 95% CI: 1.1–3.8) and female sex (OR: 8.3; 95% CI: 2.4–28.1).
Conclusions
Polypharmacy and inappropriate prescribing are highly prevalent in elderly people living with HIV. Women are at higher risk than men, partly explained by sex differences in the occurrence of non-HIV comorbidities and medical care. Medication reconciliation and periodic review of prescriptions by experienced physicians could help reduce polypharmacy and inappropriate prescribing in this vulnerable, growing population.
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