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- Bernardino, Jose I, et al.
(författare)
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Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1 : a substudy of the NEAT001/ANRS143 randomised trial
- 2015
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Ingår i: The Lancet. - 1474-547X .- 2352-3018. ; 2:11, s. 73-464
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen.METHODS: Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants.FINDINGS: Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; p<0.0001). Seven new fractures occurred during the trial (two in the NtRTI-sparing group and five in the standard group).INTERPRETATION: A raltegravir-based regimen was associated with significantly less loss of bone mineral density than a standard regimen containing tenofovir disoproxil fumarate, and might be a treatment option for patients at high risk of osteopenia or osteoporosis who are not suitable for NtRTIs such as abacavir or tenofovir alafenamide.FUNDING: The European Union Sixth Framework Programme, Inserm-ANRS, Ministerio de Sanidad y Asuntos Sociales de España, Gilead Sciences, Janssen Pharmaceuticals, and Merck Laboratories.
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- Esbjörnsson, Joakim, et al.
(författare)
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Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau : a prospective open cohort study
- 2019
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Ingår i: The Lancet HIV. - : The Lancet Publishing Group. - 2405-4704 .- 2352-3018. ; 6:1, s. E25-E31
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.
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- Frank, TD, et al.
(författare)
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Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
- 2019
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Ingår i: The lancet. HIV. - 2352-3018. ; 6:12, s. E831-E859
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Tidskriftsartikel (refereegranskat)
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- Häggblom, Amanda, et al.
(författare)
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Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy : an analysis of a prospective national cohort in Sweden.
- 2016
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Ingår i: The lancet. HIV. - 2352-3018. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- 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.FUNDING: Karolinska Institutet Research Foundation, Swedish Research Council, Stockholm County Council, Swedish Physicians against AIDS, US National Institutes of Health, University of Missouri.
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- Lippman, Sheri A, et al.
(författare)
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A community mobilisation intervention to improve engagement in HIV testing, linkage to care, and retention in care in South Africa : a cluster-randomised controlled trial
- 2022
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Ingår i: The Lancet HIV. - : Elsevier. - 2405-4704 .- 2352-3018. ; 9:9, s. e617-e626
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Tidskriftsartikel (refereegranskat)abstract
- Background: Community mobilisation, engaging communities in a process to collectively enact change, could improve HIV testing and care engagement. In South Africa, current rates fall below those needed for epidemic control. We assessed whether community mobilisation increased HIV testing, linkage to care, and retention in care over time in intervention relative to control communities.Methods: We conducted a cluster-randomised controlled trial in villages in the Agincourt sub-district of the rural Mpumalanga Province in South Africa. 15 villages were randomly assigned to either a community mobilisation intervention engaging residents to address social barriers to HIV testing and treatment (intervention arm) or to a control arm using balanced randomisation. Villages were eligible if they had been fully enumerated in 2014, had not been included in previous mobilisation activities, and included over 500 permanent adult residents aged 18–49 years. Primary outcomes included quarterly rates of HIV testing, linkage to care, and retention in care documented from health facility records among residents of the intervention and control communities over the 3-year study period. Intention-to-treat analyses employed generalised estimating equations stratified by sex. This trial is registered with ClinicalTrials.gov, NCT02197793.Findings: Between Aug 1, 2015, and July 31, 2018, residents in eight intervention communities (n=20 544 residents) and seven control communities (n=17 848) contributed data; 92 residents contributed to both arms. Among men, HIV testing increased quarterly by 12·1% (relative change [RC] 1·121, 95% CI 1·099 to 1·143, p<0·0001) in the intervention communities and 9·5% (1·095, 1·075 to 1·114, p=0·011) in the control communities; although increases in testing were greater in the intervention villages, differences did not reach significance (exponentiated interaction coefficient 1·024, 95% CI 0·997 to 1·052, p=0·078). Among women, HIV testing increased quarterly by 10·6% (RC 1·106, 95% CI 1·097 to 1·114, p<0·0001) in the intervention communities and 9·3% (1·093, 1·084 to 1·102, p=0·053) in the control communities; increases were greater in intervention communities (exponentiated interaction coefficient 1·012, 95% CI 1·001 to 1·023, p=0·043). Quarterly linkage increased significantly among women in the intervention communities (RC 1·013, 95% CI 1·002 to 1·023, p=0·018) only. Quarterly linkage fell among men in both arms, but decreased significantly among men in the control communities (0·977, 0·954 to 1·002, p=0·043). Quarterly retention fell among women in both arms; however, reductions were tempered among women in the intervention communities (exponentiated interaction coefficient 1·003, 95% CI <1·000 to 1·006, p=0·062). Retention fell significantly among men in both arms with difference in rates of decline.Interpretation: Community mobilisation was associated with modest improvements in select trial outcomes. The sum of these incremental, quarterly improvements achieved by addressing social barriers to HIV care engagement can impact epidemic control. However, achieving optimal impacts will probably require integrated efforts addressing both social barriers through community mobilisation and provision of improved service delivery.
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- Oluoch, Tom, et al.
(författare)
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Effect of a clinical decision support system on early action on immunological treatment failure in patients with HIV in Kenya: a cluster randomised controlled trial
- 2016
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Ingår i: LANCET HIV. - : ELSEVIER INC. - 2352-3018. ; 3:2, s. E76-E84
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Tidskriftsartikel (refereegranskat)abstract
- Background A clinical decision support system (CDSS) is a computer program that applies a set of rules to data stored in electronic health records to off er actionable recommendations. We aimed to establish whether a CDSS that supports detection of immunological treatment failure among patients with HIV taking antiretroviral therapy (ART) would improve appropriate and timely action. Methods We did this prospective, cluster randomised controlled trial in adults and children (aged >= 18 months) who were eligible for, and receiving, ART at HIV clinics in Siaya County, western Kenya. Health facilities were randomly assigned (1: 1), via block randomisation (block size of two) with a computer-generated random number sequence, to use electronic health records either alone (control) or with CDSS (intervention). Facilities were matched by type and by number of patients enrolled in HIV care. The primary outcome measure was the difference between groups in the proportion of patients who experienced immunological treatment failure and had a documented clinical action. We used generalised linear mixed models with random effects to analyse clustered data. This trial is registered with ClinicalTrials.gov, number NCT01634802. Findings Between Sept 1, 2012, and Jan 31, 2014, 13 clinics, comprising 41 062 patients, were randomly assigned to the control group (n=6) or the intervention group (n=7). Data collection at each site took 12 months. Among patients eligible for ART, 10 358 (99%) of 10 478 patients were receiving ART at control sites and 10 991 (99%) of 11 028 patients were receiving ART at intervention sites. Of these patients, 1125 (11%) in the control group and 1342 (12%) in the intervention group had immunological treatment failure, of whom 332 (30%) and 727 (54%), respectively, received appropriate action. The likelihood of clinicians taking appropriate action on treatment failure was higher with CDSS alerts than with no decision support system (adjusted odds ratio 3.18, 95% CI 1.02-9.87). Interpretation CDSS significantly improved the likelihood of appropriate and timely action on immunological treatment failure. We expect our findings will be generalisable to virological monitoring of patients with HIV receiving ART once countries implement the 2015 WHO recommendation to scale up viral load monitoring.
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- Wang, Haidong, et al.
(författare)
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Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
- 2016
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Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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