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| 2. |
- Botha-le Roux, Shani, et al.
(author)
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Cardiovascular Profile of South African Adults with Low-Level Viremia during Antiretroviral Therapy
- 2022
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:10
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Journal article (peer-reviewed)abstract
- Chronic inflammation is an HIV infection feature, contributing to elevated risk of cardiovascular disease among people with HIV, which can be induced by viral replication. A proportion of antiretroviral therapy (ART) recipients fail to achieve viral suppression, despite not meeting criteria for treatment failure, so-called low-level viremia (LLV). We investigated the relationship between LLV and an array of cardiovascular measures and biomarkers. South Africans with LLV (viral load = 50–999 copies/mL) and virological suppression (viral load <50 copies/mL) were selected from the EndoAfrica study (all receiving efavirenz-based ART) for cross-sectional comparison of vascular structure and function measures, as well as 21 plasma biomarkers related to cardiovascular risk and inflammation. Associations were investigated with univariate, multivariate, and binomial logistic regression analyses (having outcome measures above (cases) or below (controls) the 75th percentile). Among 208 participants, 95 (46%) had LLV, and 113 (54%) had viral suppression. The median age was 44 years, 73% were women, and the median ART duration was 4.5 years. Cardiovascular measures and biomarker levels were similar between these two categories. Cardiovascular function and structure measures were not associated with viremia status and having LLV did not increase the odds of having outcome measures above the 75th percentile. In this study among South African ART recipients, LLV did not associate with cardiovascular risk.
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| 3. |
- Brattgård, Hanna, et al.
(author)
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Factors associated with low-level viraemia in people with HIV starting antiretroviral therapy : A Swedish observational study
- 2022
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Low-level viraemia (LLV) occurs in some people with HIV (PWH) receiving antiretroviral therapy (ART) and has been linked to inferior treatment outcomes. We investigated factors associated with LLV in a nationwide cohort of Swedish PWH starting ART.METHODS: Participants were identified from the InfCareHIV register, with the following inclusion criteria: ART initiation 2006-2017, age >15 years, ≥4 viral load (VL) results available and no documented treatment interruptions or virologic failure (≥2 consecutive VL ≥200 copies/ml) during follow-up. Starting from 6 months after ART initiation, participants were followed for 24 months and categorised as viral suppression (VS; VL <50 copies/ml) or LLV (≥2 consecutive VL 50-199 copies/ml). We analysed the association between the following factors and LLV using multivariable logistic regression: sex, age, pre-ART VL and CD4 count, ART regimen, country of birth, HIV-1 subtype and transmission category.RESULTS: Among 3383 participants, 3132 (92.6%) had VS and 251 (7.4%) had LLV. In univariable analyses, factors associated with LLV were male sex, higher age, lower pre-ART CD4 count, higher pre-ART VL and ART regimen. After adjustment, the following factors were associated with LLV (adjusted odds ratio; 95% confidence interval): male sex (1.6; 1.1-2.3), higher pre-ART VL (2.7; 2.2-3.3), pre-ART CD4 count <200 cells/μl (1.6; 1.2-2.2), protease inhibitor (PI)-based regimen (1.5; 1.1-2.1), non-standard ART (2.4; 1.0-5.5) and injecting drug use (2.0; 1.1-3.7).CONCLUSION: Among Swedish PWH, LLV during ART was associated with markers of HIV disease severity before starting ART, male sex, injecting drug use and use of PI-based or non-standard ART regimens.
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- Brodin, Daniel, et al.
(author)
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Inhaled ciclesonide in adults hospitalised with COVID-19 : a randomised controlled open-label trial (HALT COVID-19)
- 2023
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:2
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19.DESIGN: Multicentre, randomised, controlled, open-label trial.SETTING: 9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021.PARTICIPANTS: Adults hospitalised with COVID-19 and receiving oxygen therapy.INTERVENTION: Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care.MAIN OUTCOME MEASURES: Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death.RESULTS: Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49-67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3-9) days in the ciclesonide group and 4 (2-7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a <1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment.CONCLUSIONS: In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully.TRIAL REGISTRATION NUMBER: NCT04381364.
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| 5. |
- Carlander, C., et al.
(author)
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Cohort profile: InfCareHIV, a prospective registry-based cohort study of people with diagnosed HIV in Sweden
- 2023
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In: Bmj Open. - : BMJ. - 2044-6055. ; 13:3
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Journal article (peer-reviewed)abstract
- Purpose The Swedish InfCareHIV cohort was established in 2003 to ensure equal and effective care of people living with HIV (PLHIV) and enable long-term follow-up. InfCareHIV functions equally as a decision support system as a quality registry, ensuring up-to-date data reported in real time. Participants InfCareHIV includes data on >99% of all people with diagnosed HIV in Sweden and up to now 13029 have been included in the cohort. InfCareHIV includes data on HIV-related biomarkers and antiretroviral therapies (ART) and also on demographics, patient-reported outcome measures and patient-reported experience measures. Findings to date Sweden was in 2015 the first country to reach the UNAIDS (United Nations Programme on HIV/AIDS)/WHO's 90-90-90 goals. Late diagnosis of HIV infection was identified as a key problem in the Swedish HIV-epidemic, and low-level HIV viraemia while on ART associated with all-cause mortality. Increased HIV RNA load in the cerebrospinal fluid (CSF) despite suppression of the plasma viral load was found in 5% of PLHIV, a phenomenon referred to as 'CSF viral escape'. Dolutegravir-based treatment in PLHIV with pre-existing nucleoside reverse transcriptase inhibitor-mutations was non-inferior to protease inhibitor-based regimens. An increase of transmitted drug resistance was observed in the InfCareHIV cohort. Lower efficacy for protease inhibitors was not due to lower adherence to treatment. Incidence of type 2 diabetes and insulin resistance was high in the ageing HIV population. Despite ART, the risk of infection-related cancer as well as lung cancer was increased in PLHIV compared with HIV-negative. PLHIV were less likely successfully treated for cervical precancer and more likely to have human papillomavirus types not included in current HPV vaccines. Self-reported sexual satisfaction in PLHIV is improving and is higher in women than men. Future plans InfCareHIV provides a unique base to study and further improve long-term treatment outcomes, comorbidity management and health-related quality of life in people with HIV in Sweden.
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| 7. |
- Elvstam, Olof, et al.
(author)
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All-Cause Mortality and Serious Non-AIDS Events in Adults with Low-Level HIV Viremia during Combination Antiretroviral Therapy: Results from a Swedish Nationwide Observational Study.
- 2021
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In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 72:12, s. 2079-2086
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Journal article (peer-reviewed)abstract
- The impact of low levels of HIV RNA (low-level viremia; LLV) during combination antiretroviral therapy (cART) on clinical outcomes is unclear. We explored the associations between LLV and all-cause mortality, AIDS, and serious non-AIDS events (SNAE).We grouped individuals starting cART 1996-2017 (identified from the Swedish InfCare HIV register) as virologic suppression (VS; <50 copies/mL), LLV (repeated viral load 50-999 copies/mL), and non-suppressed viremia (NSV; ≥1000 copies/mL). Separately, LLV was subdivided into 50-199 and 200-999 copies/mL (reflecting different definitions of virologic failure). Proportional-hazard models (including sex, age, pre-ART CD4 count and viral load, country of birth, injection drug use, treatment experience and interruptions, and an interaction term between viremia and time) were fitted for the study outcomes.6,956 participants were followed for a median of 5.7 years. At the end of follow-up, 60% were categorized as VS, 9% as LLV, and 31% as NSV. Compared with VS, LLV was associated with increased mortality (adjusted hazard ratio [aHR] 2.2, 95% confidence interval [CI] 1.3-3.6). This association was also observed for LLV 50-199 copies/mL (aHR 2.2, 95% CI 1.3-3.8), but was not statistically significant for LLV 200-999 copies/mL (aHR 2.1, 95% CI 0.96-4.7). LLV 50-999 copies/mL was not linked to increased risk of AIDS or SNAE, but in subanalysis, LLV 200-999 copies/mL was associated with SNAE (aHR 2.0, 95% CI 1.2-3.6).In this population-based cohort, LLV during cART was associated with adverse clinical outcomes.
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| 8. |
- Elvstam, Olof, et al.
(author)
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Associations between HIV viremia during antiretroviral therapy and cardiovascular disease
- 2022
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In: AIDS (London, England). - 1473-5571. ; 36:13, s. 1829-1834
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the association between HIV viremia exposure during antiretroviral therapy (ART) and cardiovascular disease (CVD) risk.DESIGN: Nationwide observational cohort.METHODS: Participants (age > 15 years) from the Swedish nationwide InfCareHIV register initiating ART 1996-2017 were categorized in a time-updated manner into four viremia categories, starting from 12 months after ART initiation: suppression (<50 copies/ml), low-level viremia (50-199 copies/ml and 200-999 copies/ml, respectively), and high-level viremia (≥1000 copies/ml). In addition, cumulative viremia was estimated as the area under the log viral load (VL) curve. Proportional subhazard models adjusted for sex, age, pre-ART CD4 and VL, injection drug use, and country of birth were used to analyze the association between viremia exposure and CVD risk (ischemic heart disease, stroke, and heart failure; data obtained by linkage to national registers), accounting for the competing risk of non-CVD death.RESULTS: In all, 337 cases of CVD were observed during 44 937 person-years of follow-up (n = 6562). Higher viremia exposure was associated with CVD, both when parameterized as cumulative viremia (adjusted subhazard ratio [aSHR] per 1 log10 copy × year/ml, 1.03; 95% confidence interval [CI], 1.01-1.05) and as viremia category (aSHR for high-level viremia versus suppression, 1.45; 95% CI, 1.03-2.05). We observed no association between CVD and low-level viremia compared with those with suppression.CONCLUSIONS: Higher exposure to HIV viremia was linked to CVD in ART recipients, whereas no increased risk was detected for people with low-level viremia compared with viral suppression. Causal inference is limited by the observational nature of this study.
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| 9. |
- Elvstam, Olof, et al.
(author)
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Associations Between Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid Levels and Incidence of Invasive Cancer in People With HIV After Initiation of Combination Antiretroviral Therapy.
- 2021
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In: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 8:6
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Journal article (peer-reviewed)abstract
- Human immunodeficiency virus (HIV) viremia could be involved in the increased risk of cancer in people with HIV (PWH) receiving combination antiretroviral therapy (cART). We analyzed the association between plasma HIV ribonucleic acid levels in PWH starting cART and incident invasive cancer using the Swedish cohort InfCare HIV linked with national registers.Adults starting cART in 1996-2017 were included if they had ≥1 viral load (VL) measurement before receiving any antiretroviral agent (pre-ART VL) and ≥2 VLs ≥6 months after start of cART. Viremia during cART was analyzed both as viremia-copy-years and categorized as suppression (<50 copies/mL), low-level viremia ([LLV] 50-999 copies/mL), and nonsuppression (≥1000 copies/mL). The main outcome was a composite of invasive malignancies with increased incidence among PWH. We fitted proportional subhazard models (including sex, age, pre-ART CD4 count, and injection drug use) for both pre-ART VL and viremia during cART.After 32 105 person-years, 3254 of 4931 participants (66%) were classified as suppressed, 438 (9%) were classified as LLV, and 1221 (25%) were classified as nonsuppressed. Neither viremia category nor cumulative viremia during cART had a statistically significant association with cancer. Higher pre-ART VL was associated with cancer (adjusted subhazard ratio, 1.4; 95% confidence interval, 1.0-1.8); this remained statistically significant with viremia during cART in the model. In subanalysis, the association with pre-ART VL was statistically significant for acquired immune deficiency syndrome (AIDS)-defining and infection-related non-AIDS-defining cancer, but not for other malignancies.In this nationwide cohort, pre-ART VL was an independent predictor of invasive cancer, whereas viremia profile during cART was not associated with cancer incidence.
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| 10. |
- Elvstam, Olof, et al.
(author)
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Difficult-to-treat HIV in Sweden: a cross-sectional study
- 2024
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In: BMC INFECTIOUS DISEASES. - 1471-2334. ; 24:1
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Journal article (peer-reviewed)abstract
- BackgroundOur aim was to examine the prevalence and characteristics of difficult-to-treat HIV in the current Swedish HIV cohort and to compare treatment outcomes between people with difficult and non-difficult-to-treat HIV.MethodsIn this cross-sectional analysis of the Swedish HIV cohort, we identified all people with HIV currently in active care in 2023 from the national register InfCareHIV. We defined five categories of difficult-to-treat HIV: 1) advanced resistance, 2) four-drug regimen, 3) salvage therapy, 4) virologic failure within the past 12 months, and 5) >= 2 regimen switches following virologic failure since 2008. People classified as having difficult-to-treat HIV were compared with non-difficult for background characteristics as well as treatment outcomes (viral suppression and self-reported physical and psychological health).ResultsNine percent of the Swedish HIV cohort in 2023 (n = 8531) met at least one criterion for difficult-to-treat HIV. Most of them had >= 2 regimen switches (6%), and the other categories of difficult-to-treat HIV were rare (1-2% of the entire cohort). Compared with non-difficult, people with difficult-to-treat HIV were older, had an earlier first year of positive HIV test and lower CD4 counts, and were more often female. The viral suppression rate among people with difficult-to-treat HIV was 84% compared with 95% for non-difficult (p = 0.001). People with difficult-to-treat HIV reported worse physical (but not psychological) health, and this remained statistically significant after adjustment for age, sex, and transmission group.ConclusionsAlthough 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed, and challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.
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