Veronica Svedhem

Sweden, the first country to achieve the Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90-90-90 continuum of HIV care targets

The Joint United Nations Programme on HIV/AIDS (UNAIDS)/World Health Organization (WHO) 90‐90‐90 goals propose that 90% of all people living with HIV should know their HIV status, 90% of those diagnosed should receive antiretroviral therapy (ART), and 90% of those should have durable viral suppression. We have estimated the continuum of HIV care for the entire HIV‐1‐infected population in Sweden.

Kinetics of HIV-1 RNA and resistance-associated mutations after cessation of antiretroviral combination therapy.

ObjectiveTo study the kinetics of HIV-1 RNA and drug-induced mutations after cessation of antiretroviral therapy (ART). Design and methodsSuccessive plasma samples from 26 patients were tested for HIV-1 RNA by PCR and for mutations associated with drug resistance by sequencing of the pol gene. ResultsAfter cessation of ART the phase of undetectable virus (< 50 copies/ml), ranging from 6 to more than 29 days, was followed by a rapid viral increase, which slowed down before a plateau corresponding to pre-treatment levels or higher was reached in most cases (14/19 patients). In one patient virus was still undetectable at 4 weeks. Also, a significantly larger number of primary protease inhibitor (PI)-associated mutations reverted to wild-type, as compared with secondary PI-, and primary reverse transcriptase inhibitor (RTI)-associated mutations. During the rapid viral increase no mutations disappeared, which instead happened during the slower viral increase preceding the viral plateau level. ConclusionAfter discontinuation of ART large individual variations were found for the time period until HIV-1 became detectable in plasma, possibly due to differences in the HIV-1 specific immunity. The more rapid loss of primary PI mutations suggests that they might cause a more impaired viral fitness than primary RTI mutations. However, the persistence of drug mutations during the initial viral load increase indicates that mutated strains may still replicate efficiently.

Treatment of HIV infection: Swedish recommendations 2009

On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/µl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.

Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy: an analysis of a prospective national cohort in Sweden

BACKGROUNDnPeople with HIV-1 in low-income and middle-income countries increasingly need second-line regimens with boosted protease inhibitors. However, data are scarce for treatment response in patients with HIV-1 subtype C (HIV-1C), which is predominant in these regions. We aimed to examine factors associated with virological failure in patients in a standardised national health-care setting.nnnMETHODSnWe analysed data for participants in InfCare HIV, a prospective national cohort that includes more than 99% of people with HIV in Sweden. We extracted data for the cohort from the InfCare HIV database on Jan 14, 2015. Baseline was initiation of antiretroviral therapy. We used logistic regression to assess factors associated with primary virological failure (failure to suppress HIV-1 within 9 months) in patients with HIV-1B and HIV-1C and calculated odds ratios (OR) for failure. We also used Cox regression models to calculate hazard ratios (HR) for time-to-secondary virological failure (detectable viral load after initial virological suppression). We did homology-based molecular modelling to assess docking.nnnFINDINGSnWe included 1077 patients with HIV-1B and 596 with HIV-1C. In multivariate regression analysis, pre-therapy higher viral load (OR 1·82, 95% CI 1·49-2·21; p<0·0001), subtype C infection (1·75, 1·06-2·88; p=0·028), and boosted protease inhibitor-based regimens (1·55, 1·45-2·11; p=0·004) were associated with increased risk of primary virological failure. Individuals with HIV-1C who were given therapy with boosted protease inhibitors had earlier time-to-secondary virological failure than did those with HIV-1B given similar regimens (adjusted HR 1·92, 95% CI 1·30-2·83; p=0·002). Molecular modelling suggested lower affinity for protease inhibitors to HIV-1C protease than to HIV-1B.nnnINTERPRETATIONnOur findings suggest an increased risk of virological failure in patients with HIV-1C, especially in those on boosted protease inhibitor-based regimens. Future studies should further dissect the biochemical and viral mechanisms of resistance to protease inhibitors in patients with non-B subtypes of HIV-1, including clinical studies to assess the efficacy of boosted protease inhibitor-based regimens in low-income and middle income countries.nnnFUNDINGnKarolinska Institutet Research Foundation, Swedish Research Council, Stockholm County Council, Swedish Physicians against AIDS, US National Institutes of Health, University of Missouri.

Differential Effects of Efavirenz, Lopinavir/r, and Atazanavir/r on the Initial Viral Decay Rate in Treatment Naïve HIV-1–Infected Patients

Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukeys post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.

Antiretroviral treatment for HIV infection: Swedish recommendations 2016

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 1. Levels of evidence and recommendation (http://www.Cebm.Net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/).Quality grading of evidence base1a Systematic review (with homogeneity) of randomized controlled trials1b Individual randomized controlled trials with narrow confidence intervals1c ‘All or none’ all patients died before the treatment became available, but some now survive on it; or when some patients died before the treatment became available, but none now die on it.2a Systematic review (with homogeneity) of cohort studies2b Individual cohort study (including low quality RCT; e.g., <80% follow-up)2c ‘Outcomes’ Research; Ecological studies3a Systematic review (with homogeneity) of case–control studies3b Individual case–control study4 Case series (and poor quality cohort and case-control studies)5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or ‘first principles’Grading of recommendationsA. Based on evidence level 1a, b or c.B. Based on evidence level 2a, b or c, 3a or b.C. Based on evidence level 4 D Based on evidence level 5.

Disseminated Infection with Encephalitozoon intestinalis in AIDS Patients: Report of 2 Cases

Microsporidiosis must be regarded as a late opportunistic infection when HIV is advanced. In this article we describe 2 cases of disseminated infection with Encephalitozoon intestinalis. The first case had a local intestinal infection for > 1 y before it disseminated and microsporidia were found intracellularly in sputum. In the second case, spores were initially found in conjunctival cells, sinus lavage, sputum and urine. This patient had clinical symptoms and radiological findings from the central nervous system. Signs of cerebral lymphoma developed after treatment of the opportunistic microsporidial infection.

High Concordance between Self-Reported Adherence, Treatment Outcome and Satisfaction with Care Using a Nine-Item Health Questionnaire in InfCareHIV

Background In this cross-sectional study we present an integrated analysis of a self-reported Health Questionnaire and socio-demographic and treatment outcome data from the national Swedish HIV cohort, InfCareHIV. Objectives To evaluate the Health Questionnaire and identify the main determinants of adherence. Methods A total of 2,846 patients answered a nine-item disease-specific Health Questionnaire between 2012 and 2014, corresponding to 44% of all active patients in the national InfCareHIV cohort. The questionnaire assessed patient related outcome measures (PROMs) regarding health and antiretroviral treatment (ART) and patient related experience measures (PREMs) regarding involvement in care and satisfaction with the care provider. Result We found the Health Questionnaire to be valid and reliable when used in ordinary clinical practice. There was a high concordance between self-reported adherence to ART in the past seven days and treatment outcome, with 94% of patients who reported optimal adherence having a viral load <50 copies/ml. The main determinants of optimal adherence were heterosexual transmission path, being born in Sweden, being male, not reporting experience of ART side effects and being fully satisfied with care. Conclusion The nine-item Health Questionnaire can identify patients at risk of treatment failure, those in need of clinical assessment of adverse events and those with impaired physical health.

A high rate of HIV‐1 acquisition post immigration among migrants in Sweden determined by a CD4 T‐cell decline trajectory model

There is a lack of knowledge about the extent to which migrants become HIV‐1 infected after arrival in European countries. The objective of this study was to assess the extent to which migrants to Sweden become HIV‐1 infected post immigration using a CD4 T‐cell decline trajectory model.

Impact of immunosuppression and region of birth on risk of cervical intraepithelial neoplasia among migrants living with HIV in Sweden.

Little is known about the incidence and risk of cervical intraepithelial neoplasia (CIN) grade 3, adenocarcinoma in situ and invasive cervical cancer (CIN3+) among migrants living with HIV in a European setting. We assessed the cumulative incidence (CuI) and hazard ratio (HR) of CIN2+ and CIN3+ in a cohort of women living with HIV (WLWH) (nu2009=u2009893) identified from the Swedish national HIV register and HIV‐negative women (nu2009=u2009205,842) identified from the Swedish Population Register, matched on region of birth and age. Data was collected between 1993 and 2011 by linking our cohort with the Swedish National Cervical Screening Registry, collecting all cytological and histological results since 1993. The CuI of CIN3+ was 13.1% [95% confidence interval (CI) 8.9–17.2] for WLWH and 2.1% (95% CI 2.0–2.2) for HIV‐negative after 18 years of follow‐up. WLWH had more than eight times higher, age and region of birth matched, risk of CIN3+ than HIV‐negative (HR 8.8: 95% CI 6.9–11.3). WLWH born in the East region, dominated by Thai women, had a two times higher risk of CIN3+ compared with WLWH born in Sweden (HR 2.47: 95% CI 1.2–5.0), which remained after adjusting for immunosuppression. Our results showed a substantially increased risk of CIN3+ among WLWH, which differed depending on birth region. Early HIV diagnosis and attendance to cervical cancer screening, with focus on migrants, is of crucial importance to minimize the incidence of cervical intraepithelial neoplasia.