BackgroundHIV-1 subtype B (HIV-1B) still dominates in resource-rich countries but increased migration contributes to changes in the global subtype distribution. Also, spread of non-B subtypes within such countries occurs. The trend of the subtype distribution from the beginning of the epidemic in the country has earlier not been reported in detail. Thus the primary objective of this study is to describe the temporal trend of the subtype distribution from the beginning of the HIV-1 epidemic in Sweden over three decades.MethodsHIV-1 pol sequences from patients (n = 3967) diagnosed in Sweden 1983– 2012, corresponding to >40% of patients ever diagnosed, were re-subtyped using several automated bioinformatics tools. The temporal trends of subtypes and recombinants during three decades were described by a multinomial logistic regression model.ResultsAll eleven group M HIV-1 subtypes and sub-subtypes (78%), 17 circulating recombinant forms (CRFs) (19%) and 32 unique recombinants forms (URF) (3%) were identified. When all patients were analysed, there was an increase of newly diagnosed HIV-1C (RR, 95%CI: 1.10, 1.06–1.14), recombinants (1.20, 1.17–1.24) and other pure subtypes (1.11, 1.07–1.16) over time compared to HIV-1B. The same pattern was found when all patients infected in Sweden (n = 1165) were analysed. Also, for MSM patients infected in Sweden (n = 921), recombinant forms and other pure subtypes increased.SignificanceSweden exhibits one of the most diverse subtype epidemics outside Africa. The increase of non-B subtypes is due to migration and to a spread among heterosexually infected patients and MSM within the country. This viral heterogeneity may become a hotspot for development of more diverse and complex recombinant forms if the epidemics converge.

BackgroundSuccessful treatment reduces morbidity, mortality and transmission of HIV. We evaluated trends in the treatment status of HIV infected individuals enrolled in care in Sweden and Denmark during the years 1995-2010. Our aim was to assess the proportion of HIV-infected individuals who received services along the continuum of care in Denmark in 2010, and to discuss the findings in relation to the organization of the health care system.MethodsWe analyzed CD4 counts and viral loads (VL) among all HIV patients enrolled in the cohort. For each month of the study period we estimated the proportions of patients who 1) had initiated highly active antiretroviral treatment (HAART) and had VL<500 copies/mL, 2) were not eligible for HAART, 3) had initiated HAART but had VL≥500 copies/mL, 4) were eligible for, but had not initiated HAART and 5) had initiated HAART but no VL monitoring for >13 months or 6) no HAART or monitoring of CD4 for >13 months. Patients fulfilling criteria 1 or 2 were considered successfully managed.ResultsThe proportion of successfully managed patients continued to increase throughout the study period and reached 83% in 2010, 92% of Swedish/Danish men who have sex with men and heterosexual patients, but only 74% of immigrants and 78% of injection drug users were successfully managed due to higher rates of inadequate monitoring in the latter two groups. In 2010, 70% of all individuals diagnosed with HIV in Denmark were virally suppressed.ConclusionIn a public health care system with free access to specialized care, successful management of the majority of HIV patients is achievable. Interventions tailored to retain immigrants and injection drug users in care are needed to further reduce the proportion of sub-optimally treated HIV patients.

Summary Background People 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. Methods We 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. Findings We 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. Interpretation Our 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.