| 1. |
- Carlander, Christina
(författare)
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Cervical intraepithelial neoplasia in migrant women living with HIV
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to study high-grade cervical intraepithelial neoplasia (CIN) in women living with HIV (WLWH) in Sweden compared with HIV-negative women (HNW) of the same region of birth. In Paper I we assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN3, adenocarcinoma, and invasive cervical cancer (CIN3+) in a cohort of WLWH (n = 893) and HNW (n = 205 842) by linking the Swedish national HIV registry (InfCare HIV) with the Swedish Population Registry (SPR) and the Swedish National Cervical Screening Registry (NKCx). The CuI of CIN3+ was 13.1% (95% CI 8.9-17.2) and 2.1% (95% CI 2.0-2.2) for WLWH and HNW, respectively. WLWH had more than eight times higher risk of CIN3+ than HNW (HR 8.8: 95% CI 6.9–11.3), increasing with the level of immunosuppression. The highest risk was seen in WLWH born in the East region, dominated by Thai women. In Paper II we analysed if the prevalence of undiagnosed HIV in women diagnosed with CIN2+ (n = 62 874) in the counties of Stockholm and Gothenburg, Sweden, would reach the threshold of 0.1%, which has been suggested cost-effective for HIV-testing. The proportion of undiagnosed HIV was calculated by linking NKCx with InfCare HIV and did not exceed 0.1% in all women, indicating that HIV-testing all women with CIN2+ in Sweden may not be cost-effective. However the proportion of undiagnosed HIV exceeded 0.1% among migrant women diagnosed with CIN2+ suggesting that HIVtesting should routinely be performed in this population. In Paper III we assessed outcome after treatment of CIN2+ in 140 WLWH and 284 HNW, matched for country of birth, identified by linking NKCx with InfCare HIV and SPR. WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% CI 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0: 95% CI 2.1-11.6) than HNW. Suppressive (HIV-RNA<50 copies/mL) antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced odds ratio of treatment failure (OR 0.3: 95% CI 0.1-0.8). In Paper IV we studied whether HPV genotypes in women with CIN2+, identified in paper III, differed depending on their HIV status. Cervical tissue blocks of included women were retrieved from bio banks and HPV type was identified using modified general primer PCR and Luminex genotyping. WLWH were less likely to be infected with HPV 16 (prevalence ratio [PR] 0.6: 95% CI 0.35-0.97), and more likely to be infected with multiple high-risk (HR) HPV (PR 2.1, 95% CI 1.17-3.79). Only 25% of WLWH vs. 47% of HNW had HR HPV types that are covered by the bivalent and quadrivalent HPV vaccines (HPV 16 and/or 18) (PR 0.6: 95% CI 0.38-0.97). In summary, my thesis showed that WLWH in Sweden are at higher risk of developing CIN3+, have poorer outcome after treatment of CIN2+, and less proportion of HPV 16 than HNW. We also found level of immunosuppression and, for the first time, suppressive ART to be associated with effective treatment of CIN2+. We recommend migrants diagnosed with CIN2+ to be HIV-tested. Early HIV diagnosis, access and adherence to ART, HPV vaccination of young people living with HIV and those at high-risk of HIV-infection, and finally access and adherence to cervical cancer screening are all crucial to minimize the incidence of CIN2+ and its progression to ICC in WLWH.
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| 2. |
- Carlander, Christina, et al.
(författare)
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Employment by HIV status, mode of HIV transmission and migrant status : a nation-wide population-based study
- 2021
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Ingår i: AIDS. - : Wolters Kluwer. - 0269-9370 .- 1473-5571. ; 35:1, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare employment in people by HIV status, mode of HIV transmission and migrant status.Design: Nation-wide population-based register data from 1996 to 2016.Methods: All people born between 1940 and 2000 (n = 8587 629) were identified from the Swedish Total Population Register and linked to the Swedish National HIV Register (n = 9492) and Longitudinal Integration Database for Health Insurance and Labour Market Studies. Adjusted prevalence ratios (adjPR) of employment were calculated using Poisson regression. Trends in employment were illustrated in scatterplots with overlaid prediction plots.Results: People with HIV were less likely employed than HIV-negative but with decreasing difference over time [adjPR 0.57, 95% confidence interval (CI) 0.54–0.60 in 1996, adjPR 0.84, 95% CI 0.83–0.86 in 2016]. Female migrants with HIV had the highest increase of employment over time and were more likely employed than HIV-negative female migrants by end of follow-up (adjPR 1.12, 95% CI 1.08–1.16). Swedish-born with present/former intravenous drug use had the lowest employment rates. Individuals with undetectable HIV-RNA viral levels showed higher employment rates (adjPR 1.29, 95% CI 1.20–1.38) compared with those with detectable viral levels.Conclusion: Employment in people living with HIV (PLWH) increased over time but remained lower than for HIV-negative people. HIV was not associated with lower employment in migrants by end of follow-up, indicating that HIV is not a barrier for employment among migrants in Sweden. The heterogeneity of PLWH needs to be taken into account in interventions, and future studies, focusing on access to the labour market in PLWH.
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| 3. |
- Carlander, Christina, et al.
(författare)
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HPV Types in Cervical Precancer by HIV Status and Birth Region : A Population-Based Register Study
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 29:12, s. 2662-2668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status.Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons.Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35.Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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| 4. |
- Carlander, Christina, et al.
(författare)
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Nonvaccine human papillomavirus genotype common in women with HIV failing cervical precancer treatment
- 2021
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Ingår i: AIDS. - : Wolters Kluwer. - 0269-9370 .- 1473-5571. ; 35:14, s. 2367-2374
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess failure after treatment of high-grade cervical intraepithelial neoplasia (CIN2+) by HIV status and human papillomavirus (HPV) type.Design: A population-based register study.Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ sometime between 1983 and 2014 (n = 179). HIV-negative controls with CIN2+, were matched (2 : 1) for country of birth. CIN2+ biopsies were retrieved from biobanks and genotyped. Absolute risk and adjusted odds ratios (adjOR) of treatment failure by HIV status given HPV type (HPV16/18 vs. non-HPV16/18) were calculated.Results: HPV16 (32%) and HPV35 (24%) dominated in women living with HIV (WLWH) with failure, HPV35 mainly in women born in sub-Saharan Africa (67%). The absolute risk of failure in women with HPV16/18 was 26% [95% confidence interval (95% CI) 14-44] in WLWH and 12% in HIV-negative (95% CI 7-19). The absolute risk of failure in women with non-HPV16/18 was 20% (95% CI 12-31) in WLWH and 5% in HIV-negative (95% CI 2-11). WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative (adjOR 6.1, 95% CI 2.0-18.6).Conclusion: HPV35, not included in current HPV vaccines, was the second most common type in WLWH with failure. WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative. This could have implications for surveillance and vaccination post CIN2+ treatment, particularly in WLWH from sub-Saharan Africa.
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| 5. |
- Carlander, Christina, et al.
(författare)
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Suppressive antiretroviral therapy associates with effective treatment of high-grade cervical intraepithelial neoplasia
- 2018
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Ingår i: AIDS. - : LIPPINCOTT WILLIAMS & WILKINS. - 0269-9370 .- 1473-5571. ; 32:11, s. 1475-1484
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess if women living with HIV (WLWH) have poorer outcome after treatment of cervical intraepithelial neoplasia grade 2, grade 3, adenocarcinoma in situ or cervical cancer (CIN2+) than HIV-negative women (HNW) and to identify predictors of CIN2+ treatment failure and recurrence in WLWH. Design: Population-based cohort study with follow-up between 1983 and 2015. Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ (n = 179) sometime between 1983 and 2014. For each WLWH, two HNW resident in the same counties and matched for country of birth, diagnosed with CIN2+, were chosen as controls. Treatment failure was defined as the presence of CIN2+ at initial follow-up. Recurrence was defined as the presence of CIN1+ subsequent to an initial normal follow-up. Results: WLWH were three times more likely to have treatment failure (odds ratio (OR) 3.7 [95% confidence interval (CI) 2.0-6.8]) and five times more likely to recur (hazard ratio 5.0 [95% CI 2.1-11.6]) than HNW. Suppressive antiretroviral therapy (ART) at time of treatment of CIN2+ was associated with reduced OR of treatment failure (OR 0.3 [95% CI 0.1-0.8]). Immunosuppression (CD4(+) cell count < 200 cells/mu l) associated strongly with treatment failure (OR compared with CD4 (+) cell count >= 500: 8.5 [95% CI 2.3-30.7]). Conclusion: Suppressive ART is associated with effective treatment of CIN2+. Early HIV diagnosis and ART are essential for successful CIN2+ treatment.
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| 6. |
- Dinh, Sofia, et al.
(författare)
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Extracutaneous Kaposi sarcoma risk remains higher in people with HIV in the post-ART era
- 2023
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Ingår i: AIDS (London, England). - 1473-5571. ; 37:13, s. 2041-2048
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess Kaposi sarcoma (KS) by HIV-status in Sweden 1983-2017, with particular focus on extracutaneous KS. DESIGN: Population-based study linking the Total Population Registry, the Swedish HIV Registry InfCareHIV, and the Swedish Cancer Registry. METHODS: We included all Swedish residents, born in or outside Sweden between 1940 and 2000 ( n =8 587 829), assessing the annual incidence of KS, adjusted hazard ratios (adjHR), and odds ratios (adjOR) in the pre and postcombination antiretroviral therapy (ART) eras. RESULTS: KS was found in 324 individuals of whom 202 (62%) were people with HIV (PWH). While the incidence of KS decreased in PWH, it remained higher compared to HIV-negative at end of follow-up (28 vs. 0.09 per 100 000 person-years, P <0.001). In the post-ART era, PWH still had an increased risk of both cutaneous [adjHR 616, 95% confidence interval (CI) 410-926] and extracutaneous KS (adjHR 2068, 95% CI 757-5654), compared to HIV-negative individuals, although there were no cases of extracutaneous disease among virally suppressed PWH. In the post-ART era, the relative risk for KS remained higher in men, particularly men who have sex with men, and viral suppression was associated with lower odds of KS (adjOR 0.05, 95% CI 0.03-0.09). CONCLUSIONS: KS remained increased in PWH in the post-ART era, with a particularly high risk for extracutaneous disease compared to HIV-negative individuals. Notably, there were no cases of extracutaneous disease among virally suppressed PWH, suggesting a less aggressive disease in this population. Further studies on KS in virally suppressed PWH are warranted.
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| 7. |
- 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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| 8. |
- Eriksen, Jaran, et al.
(författare)
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Antiretroviral treatment for HIV infection: Swedish recommendations 2016.
- 2017
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:1, s. 1-34
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases. First-line treatment for previously untreated individuals includes dolutegravir, boosted darunavir or efavirenz with either abacavir/lamivudine or tenofovir (TDF/TAF)/emtricitabine. Pre-exposure prophylaxis (PrEP) is recommended for high-risk individuals. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine ( http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ ) ( Table 1 ). This document does not cover treatment of opportunistic infections and tumours. [Table: see text].
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| 9. |
- Gaines, Hans, et al.
(författare)
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Six-week follow-up after HIV-1 exposure: a position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
- 2016
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:2, s. 93-98
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Forskningsöversikt (refereegranskat)abstract
- In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.
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| 10. |
- Krifors, Anders, et al.
(författare)
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The clinical impact of implementing GenMark ePlex blood culture panels for around-the-clock blood culture identification; a prospective observational study
- 2020
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Ingår i: Infectious Diseases. - : TAYLOR & FRANCIS LTD. - 2374-4235 .- 2374-4243. ; 52:10, s. 705-712
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Tidskriftsartikel (refereegranskat)abstract
- Background:Implementing rapid molecular blood culture diagnostics in the clinical management of sepsis is essential for early pathogen identification and resistance gene testing. The GenMark ePlex blood culture panels offer a broad microbial spectrum with minimal hands-on time and approximately 1.5 h to result. Therefore, ePlex can be utilized at times when the clinical microbiology laboratory is unavailable. Methods:From 23 October 2019 to 30 December 2019, consecutive non-duplicate positive blood cultures signalling microbial growth at the 24 h/7 days-a-week available clinical chemistry laboratory between 9 pm and 7 am were analysed with ePlex. All blood cultures were transported to the microbiology laboratory the following day for conventional identification and antibiotic susceptibility testing. Results:We used ePlex to test 91 blood cultures, of which 86 had confirmed microbial growth. Eighty-one were positive for ePlex target pathogens. The ePlex results were in complete agreement with conventional methods in 72/81 (88.9%) of cases and available within a median of 10.9 h earlier. Resistance gene targets (11mecA and 1 CTX-M) were concordant with phenotypic susceptibility in all cases. In 18/86 (20.9%) of the patient cases, there was an opportunity to optimize antimicrobial therapy based on the ePlex result. The ePlex result affected clinical decision-making in 4/86 (4.7%) of the cases and reduced the average time to effective antimicrobial therapy by 8.9 h. Conclusions:Our implementation of ePlex is a feasible option to attain around-the-clock blood culture identification in many hospitals. It can significantly reduce time-to-pathogen identification and have an impact on clinical decision-making.
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