| 1. |
- Tesfaye, Fregenet, et al.
(författare)
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Alternative biomarkers for classification of latent tuberculosis infection status in pregnant women with borderline Quantiferon plus results
- 2020
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Ingår i: Tuberculosis. - : Elsevier BV. - 1472-9792. ; 124
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Tidskriftsartikel (refereegranskat)abstract
- Borderline interferon-gamma (IFN-γ) results (near the cut-off level 0.35 IU/ml) occur in QuantiFERON (QFT) assays. We investigated the performance of alternative biomarkers for classification of latent tuberculosis infection (LTBI) status in pregnant women with borderline QFT IFN-γ responses. Pregnant women (n = 96) were identified from a cohort study in Ethiopia, based on QFT-Plus IFN-γ results (QFT-low: <0.20 IU/ml, n = 33; QFT-borderline: 0.20–0.70 IU/ml, n = 31; QFT-high: >0.70 IU/ml, n = 32), including 12 HIV-positive individuals in each group and with 20 HIV-negative non-pregnant women from the same cohort with QFT IFN-γ <0.20 IU/ml as controls. Concentrations of 8 markers (IL-1ra, IL-6, IL-8, IP-10, MCP-1, MCP-2, osteopontin and resistin) were measured in whole blood QFT supernatants, stimulated separately with TB1 and TB2 antigens. K-nearest neighbor analysis (KNN) was used to classify participants with regard to likelihood of LTBI. Concentrations of MCP-2, IP-10 and IL-1ra were higher in QFT-borderline compared to QFT-low participants in both antigen stimulations (p < 0.001). KNN classification indicated high likelihood of LTBI in 13/31 (42%) women with QFT-borderline IFN-γ results. MCP-2, IP-10 and IL-1ra expressed in whole blood after TB antigen stimulation may be considered as alternative biomarkers for classification of LTBI status in pregnant women with borderline QFT IFN-γ results.
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| 2. |
- Arimide, Dawit Assefa, et al.
(författare)
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High Level of HIV Drug Resistance and Virologic Nonsuppression among Female Sex Workers in Ethiopia : A Nationwide Cross-Sectional Study
- 2022
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - 1525-4135. ; 89:5, s. 566-574
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia.Methods:A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify factors associated with VLN and HIVDR.Results:Among 4900 participants, 1172 (23.9%) were HIV-positive and 1154 (98.5%) had a VL result. Participants were categorized into antiretroviral therapy (ART) (n = 239) and ART-naive (n = 915) groups based on self-report. From the 521 specimens (ART, 59; ART-naive, 462) with VL ≥1000 copies/mL, genotyping was successful for 420 (80.6%) and 92 (21.9%) had drug resistance mutations (DRMs). Pretreatment drug resistance (PDR) was detected in 16.5% (63/381) of the ART-naive participants. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTIs (NNRTIs), and dual-class DRMs were detected in 40 (10.5%), 55 (14.4%), and 35 (9.2%) of the participants, respectively. Among 239 participants on ART, 59 (24.7%) had VLN. Genotyping was successfully performed for 39 (66.1%). DRMs were detected in 29 (74.4%). All 29 had NNRTI, 23 (79.3%) had NRTI or dual-class DRMs. VLN was associated with age 35 years or older, CD4+T-cell count <350 cells/mm3, and being forced into selling sex. PDR and acquired drug resistance were associated with CD4+T-cell count <350 cells/mm3(P < 0.001).Conclusions:The high VLN and HIVDR rates among FSWs underscore the need for targeted interventions to improve ART access and virologic monitoring to maximize the benefit of ART and limit the spread of HIV and HIVDR.
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| 3. |
- Arimide, Dawit Assefa, et al.
(författare)
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Molecular Epidemiology and Transmission Dynamics of the HIV-1 Epidemic in Ethiopia : Epidemic Decline Coincided With Behavioral Interventions Before ART Scale-Up
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ethiopia is one of the sub-Saharan countries hit hard by the HIV epidemic. Previous studies have shown that subtype C dominates the Ethiopian HIV-1 epidemic, but the evolutionary and temporal dynamics of HIV-1 in Ethiopia have not been closely scrutinized. Understanding the evolutionary and epidemiological pattern of HIV is vital to monitor the spread, evaluate and implement HIV prevention strategies. Methods: We analyzed 1,276 Ethiopian HIV-1 subtype C polymerase (pol sequences), including 144 newly generated sequences, collected from different parts of the country from 1986 to 2017. We employed state-of-art maximum likelihood and Bayesian phylodynamic analyses to comprehensively describe the evolutionary dynamics of the HIV-1 epidemic in Ethiopia. We used Bayesian phylodynamic models to estimate the dynamics of the effective population size (Ne) and reproductive numbers (Re) through time for the HIV epidemic in Ethiopia. Results: Our analysis revealed that the Ethiopian HIV-1 epidemic originated from two independent introductions at the beginning of the 1970s and 1980s from eastern and southern African countries, respectively, followed by epidemic growth reaching its maximum in the early 1990s. We identified three large clusters with a majority of Ethiopian sequences. Phylodynamic analyses revealed that all three clusters were characterized by high transmission rates during the early epidemic, followed by a decline in HIV-1 transmissions after 1990. Re was high (4–6) during the earlier time of the epidemic but dropped significantly and remained low (Re < 1) after the mid-1990. Similarly, with an expected shift in time, the effective population size (Ne) steadily increased until the beginning of 2000, followed by a decline and stabilization until recent years. The phylodynamic analyses corroborated the modeled UNAIDS incidence and prevalence estimates. Conclusion: The rapid decline in the HIV epidemic took place a decade before introducing antiretroviral therapy in Ethiopia and coincided with early behavioral, preventive, and awareness interventions implemented in the country. Our findings highlight the importance of behavioral interventions and antiretroviral therapy scale-up to halt and maintain HIV transmissions at low levels (Re < 1). The phylodynamic analyses provide epidemiological insights not directly available using standard surveillance and may inform the adjustment of public health strategies in HIV prevention in Ethiopia.
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| 4. |
- Arimide, Dawit Assefa, et al.
(författare)
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Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia
- 2022
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 14:4
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Tidskriftsartikel (refereegranskat)abstract
- Dolutegravir-based antiretroviral therapy (ART) has been scaled up in many developing countries, including Ethiopia. However, subtype-dependent polymorphic differences might influence the occurrence of HIV-drug-resistance mutations (HIVDRMs). We analyzed the prevalence of pre-treatment integrase strand transfer inhibitor (INSTI) HIVDRMs and naturally occurring polymorphisms (NOPs) of the integrase gene, using plasma samples collected as part of the national HIVDR survey in Ethiopia in 2017. We included a total of 460 HIV-1 integrase gene sequences from INSTI-naïve (n = 373 ART-naïve and n = 87 ART-experienced) patients. No dolutegravir-associated HIVDRMs were detected, regardless of previous exposure to ART. However, we found E92G in one ART-naïve patient specimen and accessory mutations in 20/460 (4.3%) of the specimens. Moreover, among the 288 integrase amino acid positions of the subtype C, 187/288 (64.9%) were conserved (<1.0% variability). Analysis of the genetic barrier showed that the Q148H/K/R dolutegravir resistance pathway was less selected in subtype C. Docking analysis of the dolutegravir showed that protease-and reverse-transcriptase-associated HIVDRMs did not affect the native structure of the HIV-1 integrase. Our results support the implementation of a wide scale-up of dolutegravir-based regimes. However, the detection of polymorphisms contributing to INSTI warrants the continuous surveillance of INSTI resistance.
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| 5. |
- Björkman, Alva, et al.
(författare)
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Accuracy and diagnostic performance of doppler echocardiography to estimate mean pulmonary artery pressure in heart failure
- 2021
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Ingår i: Echocardiography. - : John Wiley & Sons. - 0742-2822 .- 1540-8175. ; 38:9, s. 1624-1631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Multiple echocardiographic algorithms have been proposed to estimate mean pulmonary artery pressure (PAPM) and assess pulmonary hypertension (PH) likelihood. We assessed the accuracy of four echocardiographic approaches to estimate PAPM in heart failure (HF) patients undergoing near-simultaneous right heart catheterization (RHC), and compared diagnostic performance to identify PH with recommendation-advised tricuspid regurgitation peak velocity (TRVmax).Methods: We employed four validated echocardiographic algorithms incorporating tricuspid regurgitation peak or mean gradient, pulmonary regurgitation peak gradient, and right ventricular outflow tract acceleration time to estimate PAPM. Echocardiographic estimates of right atrial pressure were incorporated in all algorithms but one. Association and agreement with invasive PAPM were assessed. Diagnostic performance of all algorithms to identify PH was evaluated and compared with the recommended TRVmax cut-off.Results: In 112 HF patients, all echocardiographic algorithms demonstrated reasonable association (r =.41–.65; p < 0.001) and good agreement with invasive PAPM, with relatively lower mean bias and higher precision observed in algorithms that incorporated tricuspid regurgitation peak or mean gradient. All methods demonstrated strong ability to identify PH (AUC =.70–.80; p < 0.001) but did not outperform TRVmax (AUC =.84; p < 0.001). Echocardiographic estimates of right atrial pressure were falsely elevated in 30% of patients.Conclusions: Echocardiographic estimates demonstrate reasonable association with invasive PAPM and strong ability to identify PH in HF. However, none of the algorithms outperformed recommendation-advised TRVmax. The incremental value of echocardiographic estimates of right atrial pressure may need to be re-evaluated.
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| 6. |
- Botha-le Roux, Shani, et al.
(författare)
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Cardiovascular Profile of South African Adults with Low-Level Viremia during Antiretroviral Therapy
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:10
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Brattgård, Hanna, et al.
(författare)
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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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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:5
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Båtshake, Ylva, et al.
(författare)
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Tuberculosis Infection and Disease Among Pregnant People Living in Sweden With Origin in Tuberculosis-Endemic Countries
- 2023
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Ingår i: Open Forum Infectious Diseases. - 2328-8957. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pregnancy has been associated with elevated incidence of tuberculosis (TB) disease. Since 2014, people living in Sweden with origin in TB-endemic countries have been offered screening for TB infection in antenatal care (ANC) using Quantiferon-TB assays. We assessed factors associated with TB infection in this population and determined the incidence of TB disease during pregnancy and postpartum periods with regard to ANC Quantiferon-TB results. Methods: Quantiferon-TB results obtained during ANC in Sweden, 2014-2018, were linked to data from national registers (Pregnancy Register, Patient Register and Tuberculosis Register). Factors associated with TB infection (defined as Quantiferon-TB ≥0.35 IU/mL) were identified using logistic regression analysis. Incidence of TB disease was determined with regard to pregnancy, postpartum and subsequent periods, and ANC Quantiferon-TB results. Results: Among 7638 screened individuals, 1424 (18.6%) had TB infection. Tuberculosis infection was independently associated with higher age at immigration (adjusted odds ratio, 1.04 [95% confidence interval, 1.03-1.05]; P <. 001), and was more common among people originating from Africa compared to other world regions (845/3088 [27.4%] vs 579/4550 [12.7%]; P <. 001). In total, 16 participants were diagnosed with TB disease (10 during pregnancy, 4 at <6 months after delivery, 2 at >6 months after delivery); among these, all diagnosed during pregnancy/postpartum had positive ANC Quantiferon-TB results (constituting 14/1424 [1%] of people with TB infection). Conclusions: Among pregnant people screened in Swedish ANC, TB infection was associated with higher age and African origin. All cases of TB disease reported in persons with TB infection at ANC screening occurred during pregnancy or postpartum.
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| 9. |
- Elvstam, Olof, et al.
(författare)
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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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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 72:12, s. 2079-2086
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Tidskriftsartikel (refereegranskat)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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| 10. |
- Elvstam, Olof, et al.
(författare)
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Associations between HIV viremia during antiretroviral therapy and cardiovascular disease
- 2022
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Ingår i: AIDS (London, England). - 1473-5571. ; 36:13, s. 1829-1834
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Tidskriftsartikel (refereegranskat)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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