Therapy In High-income Countries Research Articles

Estimation of Improvements in Mortality in Spectrum Among Adults With HIV Receiving Antiretroviral Therapy in High-Income Countries.

Mortality rates for people living with HIV (PLHIV) on antiretroviral therapy (ART) in high-income countries continue to decline. We compared mortality rates among PLHIV on ART in Europe for 2016-2020 with Spectrum's estimates. The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. We used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)'s European cohorts. In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996-1999 and 2016-2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9-1.2) and from 5.9 (4.4-8.1) to 1.1 (0.9-1.4) deaths per 1000 person-years among men and women, respectively. Non-AIDS-related mortality decreased from 9.1 (7.9-10.5) to 6.1 (5.8-6.5) and from 7.0 (5.2-9.3) to 4.8 (4.3-5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016-2020 (Spectrum: 7.02-7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66-4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1-3.4-fold higher in men in comparison to the ART-CC's AIDS-specific mortality rates. Spectrum's all-cause mortality estimates among PLHIV are consistent with age/country-controlled mortality observed in ART-CC, with some underestimation of mortality among women. Comparing results suggest that 60%-70% of excess deaths among PLHIV on ART in Spectrum are from non-AIDS causes.

Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later.

Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6).

Improved life expectancy of people living with HIV: who is left behind?

Improved life expectancy of people living with HIV: who is left behind?

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

BackgroundClinical guidelines vary with respect to the optimal monitoring frequency of HIV-positive individuals. We compared dynamic monitoring strategies based on evolving CD4 cell counts in virologically suppressed HIV-positive individuals.MethodsWe used data from prospective studies of HIV-positive individuals in Europe and the Americas in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. We compared three monitoring strategies, which differ with respect to the CD4 cell count threshold that is used to measure CD4 cell count and HIV-RNA every 3–6 months (when below the threshold) or every 9–12 months (when above the threshold). The strategies were defined by the thresholds 200, 350, and 500 cells/μl. We estimated hazard ratios of death and of AIDS-defining illness or death, risk ratios of virologic failure, and mean differences in CD4 cell count using inverse probability weighting to adjust for baseline and time-varying confounders.Findings47,635 eligible individuals initiated a cART regimen between January, 2000 and November, 2015 and met the eligibility criteria for our study. During follow-up, CD4 cell count and HIV-RNA were measured on average every 4 and 3.8 months, respectively. 464 individuals died (107 in threshold 200 strategy, 157 in threshold 350, and 200 in threshold 500) and 1,091 had AIDS-defining illnesses or died (267 in threshold 200 strategy, 365 in threshold 350, and 459 in threshold 500). Compared with threshold 500, the mortality hazard ratio (95% CI) was 1.05 (0.86, 1.29) for threshold 200 and 1.02 (0.91, 1.14) for threshold 350. Corresponding estimates for death or AIDS-defining illness were 1.08 (0.95, 1.22) and 1.03 (0.96, 1.12), respectively. The respective 24-month risk ratios (95% CI) of virologic failure (HIV-RNA>200 copies/ml) were 2.01 (1.17, 3.43) and 1.24 (0.89, 1.73) and 24-month mean CD4 cell count differences (95% CIs) were 0.4 (−25.5, 26.3) cells/μl and −3.5 (−16.0, 8.9) cells/μl.InterpretationOur findings suggest that decreasing monitoring to annually when CD4 cell count>200 cells/μl compared with >500 cells/μl does not worsen the short-term clinical and immunologic outcomes of virologically suppressed HIV-positive individuals, but more frequent virologic monitoring may be necessary to decrease the risk of virologic failure. Further follow-up is needed to establish the long-term safety of these strategies.

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

Comparison of dynamic monitoring strategies based on CD4 cell counts in virally suppressed, HIV-positive individuals on combination antiretroviral therapy in high-income countries: a prospective, observational study

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Socioeconomic status and response to antiretroviral therapy in high-income countries: a literature review.

It has been shown that socioeconomic factors are associated with the prognosis of several chronic diseases; however, there is no recent systematic review of their effect on HIV treatment outcomes. We aimed to review the evidence regarding the existence of an association of socioeconomic status with virological and immunological response to antiretroviral therapy (ART). We systematically searched the current literature using the database PubMed. We identified and summarized original research studies in high-income countries that assessed the association between socioeconomic factors (education, employment, income/financial status, housing, health insurance, and neighbourhood-level socioeconomic factors) and virological response, immunological response, and ART nonadherence among people with HIV-prescribed ART. A total of 48 studies met the inclusion criteria (26 from the United States, six Canadian, 13 European, and one Australian), of which 14, six, and 35 analysed virological, immunological, and ART nonadherence outcomes, respectively. Ten (71%), four (67%), and 23 (66%) of these studies found a significant association between lower socioeconomic status and poorer response, and none found a significant association with improved response. Several studies showed that adjustment for nonadherence attenuated the association between socioeconomic status and ART response. Our review provides strong support that socioeconomic disadvantage is associated with poorer response to ART. However, most studies have been conducted in settings such as the United States without universal free healthcare access. Further study in settings with free access to ART could help assess the impact of socioeconomic status on ART outcomes and the mechanisms by which it operates.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries.

There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, had CD4 cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4 cell count and HIV-RNA via inverse probability weighting. Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries.

Ageing faster with AIDS in Africa

As the AIDS epidemic matures, evidence is emerging that poorly managed HIV infection exacerbates ageing diseases, leading to increased morbidity and mortality, and that exacerbated chronic diseases should now be considered AIDS-related. 1 Justice AC Treated HIV infection is a chronic disease: the case against cause of death analyses. Int J Epidemiol. 2010; 39: 146-168 Crossref PubMed Scopus (14) Google Scholar Cohort evaluations indicate that non-AIDS cancers, pulmonary diseases, intracranial haemorrhage, osteoporosis, and age-related blindness, which might previously have been considered of low importance due to low prevalence, are becoming major causes of reduced quality of life and causes of death. 1 Justice AC Treated HIV infection is a chronic disease: the case against cause of death analyses. Int J Epidemiol. 2010; 39: 146-168 Crossref PubMed Scopus (14) Google Scholar Thanks to antiretroviral therapy, a person diagnosed HIV-positive and aged 20 years in the developed countries can expect to be alive well into their sixties, 2 Antiretroviral Therapy Cohort CollaborationLife expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008; 372: 293-299 Summary Full Text Full Text PDF PubMed Scopus (1318) Google Scholar and these settings are well equipped to deal with an ageing HIV-positive population with the availability of specialised care. The future of HIV/AIDS in Africa: a shared responsibilityOn Dec 1, 2010, people across the globe will observe World AIDS Day—a time of remembrance for those who have died and to celebrate progress in providing better access to treatment and care. But this is also a time to look to the future to ensure the sustainability of the programmes in place today. HIV/AIDS is a global epidemic, but it is most severe in sub-Saharan Africa, a region in desperate need of life-saving resources. As co-chairs of the recent report by the Institute of Medicine1 that assessed the future implications of HIV/AIDS in Africa, we believe that African nations—with the USA and other donor nations—must plan now for how to confront the burden of HIV/AIDS over the coming decades. Full-Text PDF Tracking a century of global expansion and evolution of HIV to drive understanding and to combat diseaseSince the isolation of HIV, multiple transmissions are thought to have occurred between man and other old-world primates. Assessment of samples from apes and human beings with African equatorial forest ancestry has traced the origin of HIV-1 to chimpanzees, and dated its most recent common ancestor to 1908. The evolution of HIV-1 has been rapid, which has resulted in a complex classification, worldwide spread, and intermixing of strains; at least 48 circulating recombinant forms are currently identified. Full-Text PDF

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

<h2>Summary</h2><h3>Background</h3> Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. <h3>Methods</h3> The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, and stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude mortality rates were also calculated. <h3>Findings</h3> 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude mortality rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than did men. Patients with presumed transmission via injecting drug use had lower life expectancies than did those from other transmission groups (32·6 [1·1] years <i>vs</i> 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 cell counts than in those with higher baseline counts (32·4 [1·1] years for CD4 cell counts below 100 cells per μL <i>vs</i> 50·4 [0·4] years for counts of 200 cells per μL or more). <h3>Interpretation</h3> Life expectancy in HIV-infected patients treated with combination antiretroviral therapy increased between 1996 and 2005, although there is considerable variability between subgroups of patients. The average number of years remaining to be lived at age 20 years was about two-thirds of that in the general population in these countries. <h3>Funding</h3> UK Medical Research Council, GlaxoSmithKline.