Maria Axelsson

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.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges

Summary Definitions for a 4-stage continuum of HIV care were standardized and applied to HIV surveillance and national cohort data in 11 European Union countries. These countries are nearing the UNAIDS 90-90-90 target, although reducing the proportion undiagnosed remains challenging.

New HIV diagnoses among adults aged 50 years or older in 31 European countries, 2004–15: an analysis of surveillance data

BACKGROUND The HIV burden is increasing in older adults in the European Union (EU) and European Economic Area (EEA). We investigated factors associated with HIV diagnosis in older adults in the 31 EU/EEA countries during a 12 year period. METHODS In this analysis of surveillance data, we compared data from older people (aged ≥50 years) with those from younger people (aged 15-49 years). We extracted new HIV diagnoses reported to the European Surveillance System between Jan 1, 2004, and Dec 31, 2015, and stratified them by age, sex, migration status, transmission route, and CD4 cell count. We defined late diagnosis as CD4 count of less than 350 cells per μL at diagnosis and diagnosis with advanced HIV disease as less than 200 cells per μL. We compared the two age groups with the χ2 test for difference, and used linear regression analysis to assess temporal trends. FINDINGS During the study period 54 102 new HIV diagnoses were reported in older adults. The average notification rate of new diagnoses was 2·6 per 100 000 population across the whole 12 year period, which significantly increased over time (annual average change [AAC] 2·1%, 95% CI 1·1-3·1; p=0·0009). Notification rates for new HIV diagnoses in older adults increased significantly in 16 countries in 2004-15, clustering in central and eastern EU/EEA countries. In 2015, compared with younger adults, older individuals were more likely to originate from the reporting country, to have acquired HIV via heterosexual contact, and to present late (p<0·0001 for all comparisons). HIV diagnoses increased significantly over time among older men (AAC 2·2%, 95% CI 1·2-3·3; p=0·0006), women (1·3%, 0·2-2·4; p=0·025), men who have sex with men (5·8%, 4·3-7·5; p<0·0001), and injecting drug users (7·4%, 4·8-10·2; p<0·0001). INTERPRETATION Our findings suggest that there is a compelling need to deliver more targeted testing interventions for older adults and the general adult population, such as by increasing awareness among health-care workers and expanding opportunities for provider-initiated and indicator-condition-guided testing programmes. FUNDING European Centre for Disease Prevention and Control.

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

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.

Getting more from heterogeneous HIV-1 surveillance data in a high immigration country: estimation of incidence and undiagnosed population size using multiple biomarkers

Background Most HIV infections originate from individuals who are undiagnosed and unaware of their infection. Estimation of this quantity from surveillance data is hard because there is incomplete knowledge about i) the time between infection and diagnosis (TI) for the general population and ii) the time between immigration and diagnosis for foreign-born persons. Development We developed a new statistical method for estimating the number of undiagnosed people living with HIV (PLHIV) and the incidence of HIV-1 based on dynamic modeling of heterogenous HIV-1 surveillance data. We formulated a Bayesian non-linear mixed effects model using multiple biomarkers to estimate TI accounting for biomarker correlation and individual heterogeneities. We explicitly model the probability that an HIV-1 infected foreign-born person was infected either before or after immigration to distinguish between endogenous and exogeneous incidence. The incidence estimator allows for direct calculation of the number of undiagnosed persons. Application The model was applied to surveillance data in Sweden. The dynamic biomarker model was trained on longitudinal data from 31 treatment-naïve patients with well-defined TI, using CD4 counts, BED serology, polymorphisms in HIV-1 pol sequences, and testing history. The multiple-biomarker model was more accurate than single biomarkers (mean absolute error 1.01 vs ≥ 1.95). We estimate that 813 (95% CI 780-862) PLHIV were undiagnosed in 2015, representing a proportion of 10.8% (95% CI 10.4-11.3%) of all PLHIV. Conclusions The proposed methodology will enhance the utility of standard surveillance data streams and will be useful to monitor progress towards and compliance with the 90-90-90 UNAIDS target. Key messages Combined heterogeneous HIV-1 surveillance data and biomarker data can be used to estimate both local incidence and the number of undiagnosed people living with HIV. Explicit modeling of the dynamics, heterogeneity, and correlation of multiple biomarkers over time improved estimation of time between infection and diagnosis. Explicit modeling of the probability that foreign-born persons were infected before or after immigration improves accuracy of estimates of endogenous incidence and undiagnosed persons living with HIV. The endogenous incidence of HIV-1 in Sweden is declining, despite continued immigration of HIV-1 infected persons. The proportion of undiagnosed PLHIV decreased over 2010-2015 and was estimated to be 10.8% (95% CI, 10.4-11.3%) in 2015.

Dynamics of Two Separate but Linked HIV-1 CRF01_AE Outbreaks among Injection Drug Users in Stockholm, Sweden, and Helsinki, Finland

ABSTRACT Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.

The dynamics of two separate but linked CRF01_AE outbreaks among IDUs in Stockholm and Helsinki

ABSTRACT Detailed phylogenetic analyses were performed to characterize an HIV-1 outbreak among injection drug users (IDUs) in Stockholm, Sweden, in 2006. This study investigated the source and dynamics of HIV-1 spread during the outbreak as well as associated demographic and clinical factors. Seventy Swedish IDUs diagnosed during 2004 to 2007 were studied. Demographic, clinical, and laboratory data were collected, and the V3 region of the HIV-1 envelope gene was sequenced to allow detailed phylogenetic analyses. The results showed that the Stockholm outbreak was caused by a CRF01_AE variant imported from Helsinki, Finland, around 2003, which was quiescent until the outbreak started in 2006. Local Swedish subtype B variants continued to spread at a lower rate. The number of new CRF01_AE cases over a rooted phylogenetic tree accurately reflected the transmission dynamics and showed a temporary increase, by a factor of 12, in HIV incidence during the outbreak. Virus levels were similar in CRF01_AE and subtype B infections, arguing against differences in contagiousness. Similarly, there were no major differences in other baseline characteristics. Instead, the outbreak in Stockholm (and Helsinki) was best explained by an introduction of HIV into a standing network of previously uninfected IDUs. The combination of phylogenetics and epidemiological data creates a powerful tool for investigating outbreaks of HIV and other infectious diseases that could improve surveillance and prevention.