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Large-scale HIV management in resource-limited settings has been remarkably successful in a relatively short time frame. Once combination antiretroviral therapy (cART) became more universally available, national treatment programs...
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Large-scale HIV management in resource-limited settings has been remarkably successful in a relatively short time frame. Once combination antiretroviral therapy (cART) became more universally available, national treatment programs were able to provide much of the needed therapy which was originally prioritized towards patients with the most advanced and symptomatic disease. At the time, it was thought that comprehensive laboratory monitoring for safety and efficacy was either unavailable, too expensive or would detract from the focus of providing life-saving treatment to as many individuals who needed it as possible .
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Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) cause side effects in some patients, prompting the use of either partly or fully NRTI-sparing regimens. We used data from the Swiss HIV Cohort Study to estimate t...
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Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) cause side effects in some patients, prompting the use of either partly or fully NRTI-sparing regimens. We used data from the Swiss HIV Cohort Study to estimate the effectiveness of two new dolutegravir dual regimens relative to the alternative NRTI-sparing dual regimens that our clinicians used previously. We emulated two trials by propensity score matching case patients on the dolutegravir regimen with control patients on an alternative regimen. We analysed the case control sets using a Bayesian Cox model and estimated effectiveness as the percentage still on their trial regimen without virologic failure at 48 weeks. In a comparison of partly NRTI-sparing regimens, 58 cases treated with dolutegravir were matched to 17 controls treated with boosted darunavir (both with lamivudine or emtricitabine). The estimated difference in effectiveness was 15% (95% credible interval, CrI, 2 to 33) and 12% (95% CrI 0 to 26) in two sequential analyses one year apart. In a comparison of fully NRTI-sparing regimens, 54 cases treated with dolutegravir were matched to 32 controls treated with raltegravir (both with boosted darunavir). The estimated difference in effectiveness was 9% (95% CrI -1 to 21) and 5% (95% CrI -4 to 15) in the two sequential analyses. Estimates of relative effectiveness suggest that both dolutegravir regimens are not inferior to these alternative regimens. All four regimens seem suitable for patients needing an NRTI-sparing regimen: there were few virologic failures and few treatment changes due to toxicity.
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According to guidelines all HIV/HBV co-infected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV/HBV patients in the E...
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According to guidelines all HIV/HBV co-infected patients should receive tenofovir-based combination antiretroviral therapy (cART). We aimed to investigate uptake and outcomes of tenofovir-based cART among HIV/HBV patients in the EuroSIDA study. All HBsAg+ patients followed up after 1 March 2002 were included. Changes in the proportion taking tenofovir-based cART over time were described. Poisson regression was used to investigate the relationship between tenofovir use and clinical events. 953 HIV/HBV patients were included. Median age was 41 years and patients were predominantly male (85%), white (82%) and ART experienced (88%). 697 and 256 were from Western and Eastern Europe, respectively. Fifty-five started cART during follow-up, the proportion starting with CD4<350 cells/mm3 decreased from 85% to 52% in the periods 2002-2006 to 2007-2015. Tenofovir use, among those taking cART, increased from 4% in 2002 to 73% in 2015. Compared to West, tenofovir use was lower in East in 2005 (7% vs. 42%), and remained lower in 2015 (63% vs. 76%). Among 602 patients taking tenofovir-based cART during follow-up, 155 (26%) discontinued tenofovir. Twenty-seven of all discontinuations were due to adverse effects. Only 14 started entecavir and/or adefovir after tenofovir discontinuation, whereas ten started PEG-IFN. Tenofovir use was not significantly associated with lower risk of liver-related clinical events (N=51), adjusted IRR 0.64 (95% CI 0.35-1.18) for comparing patients on tenofovir with those off tenofovir. Although use of tenofovir-based cART among HIV/HBV patients has increased across Europe, a substantial proportion are still starting cART late and are receiving suboptimal HBV therapy.
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Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, unc...
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Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results : Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant’s median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/μl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.
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Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard...
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Background Dolutegravir (DTG)–based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL’HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. Methods and findings SIMPL’HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel–Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than ?12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference ?1.2%; 95% CI ?7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI ?5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference ?1.1%; 95% CI ?9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study’s main limitations included a rather small proportion of women included, the open label design, and its short duration. Conclusions In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals.
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Background : Since the advent of combination antiretroviral therapy (cART), non-AIDS defining malignancies (NADM) have become increasingly important. We examined risk factors for NADM, including immunological, virological and soci...
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Background : Since the advent of combination antiretroviral therapy (cART), non-AIDS defining malignancies (NADM) have become increasingly important. We examined risk factors for NADM, including immunological, virological and socio-behavioral characteristics. Methods: We linked the Swiss HIV Cohort Study (SHCS) with cancer registries to identify incident cancers between 1996 and 2012. We analyzed four common NADM: anal, lung, prostate, and liver cancer. We calculated standardized incidence ratios (SIRs) and assessed the effect of time-updated CD4 and CD8 count, CD4/CD8 ratio, and HIV viral load (copies/ml) in Cox regression models. We lagged time-dependent variables for 12, 24, and 36 months and captured cumulative exposures using simple moving averages (SMA). In multivariable models, we also considered HIV transmission group, smoking, and chronic hepatitis B or C infection as potential predictors of NADM incidence. Results. Between 1996 and 2012, 563 HIV-infected individuals developed NADM, including 70 anal, 49 lung, 44 prostate, and 36 liver cancers. Compared with the general population, the SHCS exhibited higher rates of anal (SIR 76.1, 95% Confidence interval (CI) 60.2-96.2), lung (SIR 1.98, 1.50-2.62), and liver cancer (SIR 7.28, 5.25-10.1) but similar rates of prostate cancer (SIR 1.03, 0.76-1.38). Anal cancer was associated with low CD4 cell count, high CD8 cell count, men who have sex with men, and smoking. For lung cancer, the CD8 cell count was the only significant predictor identified among the immunological and virological factors. CD4 cell count, and chronic hepatitis B and C infection were predictive of liver cancer incidence. We found no evidence of any of the immunological factors being associated with prostate cancer. Conclusions: The importance of immunodeficiency (indexed by CD4 count) and immune senescence (indexed by CD8 count) differs across NADM. Immunodeficiency was an important risk factor for anal and liver cancer whereas immune senescence was associated with lung cancer and anal cancer.
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Background The use of mobile technology in health care (mobile health [mHealth]) could be an innovative way to improve health care, especially for increasing retention in HIV care and adherence to treatment. However, there is a sc...
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Background The use of mobile technology in health care (mobile health [mHealth]) could be an innovative way to improve health care, especially for increasing retention in HIV care and adherence to treatment. However, there is a scarcity of studies on mHealth among people living with HIV (PLHIV) in West and Central Africa. Objective The aim of this study was to assess the acceptability of an mHealth intervention among PLHIV in three countries of West Africa. Methods A cross-sectional study among PLHIV was conducted in 2017 in three francophone West African countries: C?te d’Ivoire, Burkina Faso, and Togo. PLHIV followed in the six preselected HIV treatment and care centers, completed a standardized questionnaire on mobile phone possession, acceptability of mobile phone for HIV care and treatment, preference of mobile phone services, and phone sharing. Descriptive statistics and logistic regression were used to describe variables and assess factors associated with mHealth acceptability. Results A total of 1131 PLHIV—643 from C?te d’Ivoire, 239 from Togo, and 249 from Burkina Faso—participated in the study. Median age was 44 years, and 76.1% were women (n=861). Almost all participants owned a mobile phone (n=1107, 97.9%), and 12.6% (n=140) shared phones with a third party. Acceptability of mHealth was 98.8%, with the majority indicating their preference for both phone calls and text messages. Factors associated with mHealth acceptability were having a primary school education or no education (adjusted odds ratio=7.15, 95% CI 5.05-10.12; P <.001) and waiting over one hour before meeting a medical doctor on appointment day (adjusted odds ratio=1.84, 95% CI 1.30-2.62; P =.01). Conclusions The use of mHealth in HIV treatment and care is highly acceptable among PLHIV and should be considered a viable tool to allow West and Central African countries to achieve the Joint United Nations Programme on HIV/AIDS 90-90-90 goals.
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Background: In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside ...
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Background: In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment na?ve patients. Methods: In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48. Results: Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10 th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape. Conclusions: Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.
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During the 4 years to the end of 2007, the number of people in low-income and middle-income countries (LMICs) receiving antiretroviral therapy (ART) increased from 400 000 to 3 million. Although early mortality and retention in ca...
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During the 4 years to the end of 2007, the number of people in low-income and middle-income countries (LMICs) receiving antiretroviral therapy (ART) increased from 400 000 to 3 million. Although early mortality and retention in care remain significant challenges, the majority of reports from LMICs have shown encouraging immunological, virological and survival outcomes. Reported rates of switching to second-line ART regimens have been lower than expected, in part due to actual rates of treatment success, but mainly because of limited access to both virological monitoring and second-line drugs. Clinicians have also been reluctant to switch therapy due to regimen cost, complexity, inconvenience and lack of subsequent treatment options. As cohorts mature andexpand and access to virological monitoring and second-line regimens increase, however, rates of diagnosed treatment failure and switch to second-line regimens will increase. As the cost of second-line regimens are currently three to 20 times more expensive than mat of first-line regimens, these increases will challenge the cost-effectiveness and sustainability of HIV- treatment programmes.
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Background Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HI...
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Background Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.
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