Life expectancy of HIV‐positive people after starting combination antiretroviral therapy: a meta‐analysis
TL;DR: A meta‐analysis was performed to assess life expectancy of HIV‐positive people after starting cART, and to quantify differences between low/middle‐ and high‐income countries.
Abstract: Objectives
Life expectancy is an important indicator informing decision making in policies relating to HIV-infected people. Studies estimating life expectancy after starting combination antiretroviral therapy (cART) have noted differences between income regions. The objective of our study was to perform a meta-analysis to assess life expectancy of HIV-positive people after starting cART, and to quantify differences between low/middle- and high-income countries.
Methods
Eight cohort studies estimating life expectancy in HIV-positive people initiating cART aged ≥ 14 years using the abridged life table method were identified. Random effects meta-analysis was used to pool estimated outcomes, overall and by income region. Heterogeneity between studies was assessed with the I2 statistic. We estimated additional years of life expected after starting cART at ages 20 and 35 years.
Results
Overall life expectancy in high-income countries was an additional 43.3 years [95% confidence interval (CI) 42.5–44.2 years] and 32.2 years (95% CI 30.9–33.5 years) at ages 20 and 35 years, respectively, and 28.3 (95% CI 23.3–33.3) and 25.6 (95% CI 22.1–29.2) additional years, respectively, in low/middle-income countries. In low/middle-income countries, life expectancy after starting cART at age 20 years was an additional 22.9 years (95% CI 18.4–27.5 years) for men and 33.0 years (95% CI 30.4–35.6 years) for women, but was similar in the two sexes in high-income countries. In all income regions, life expectancy after starting cART increased over calendar time.
Conclusions
Our results suggest that the life expectancy of HIV-positive people after starting cART has improved over time. Monitoring life expectancy into the future is important to assess how changes to cART guidelines will affect patient long-term outcomes.
Citations
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TL;DR: This analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level.
Abstract: HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15–49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa. Fine-scale estimates of the prevalence of HIV in adults across sub-Saharan Africa reveal substantial within-country variation and local differences in both the direction and rate of change in the prevalence of HIV between 2000 and 2017.
292 citations
TL;DR: This review focuses on the differential effects of contemporary antiretrovirals on systemic inflammation as heightened immune activation is linked to important co-morbidities and mortality with HIV infection.
Abstract: This review focuses on the differential effects of contemporary antiretrovirals on systemic inflammation as heightened immune activation is linked to important co-morbidities and mortality with HIV infection. Antiretroviral therapy (ART) reduces dramatically systemic inflammation and immune activation, but not to levels synchronous with HIV-uninfected populations. In one ART initiation trial, integrase inhibitors appear to reduce inflammation to a greater degree than non-nucleoside reverse transcriptase inhibitors (NNRTIs); however, it is not clear that there are beneficial effects on inflammation resulting from treatment with integrase inhibitors compared to PIs, between PIs and NNRTIs, between specific nucleoside reverse transcriptase inhibitors, or with maraviroc in ART-naive patients. In ART switch studies, changing to an integrase inhibitor from a PI-, NNRTI-, or enfuvirtide-containing regimen has resulted in improvement in several markers of inflammation. Additional research is needed to conclusively state whether there are clear differences in effects of specific antiretrovirals on inflammation and immune activation in HIV.
146 citations
TL;DR: A critical priority is to aim for healthy aging among people living with HIV (PLWH) in order to reach the UNAIDS 90– 90–90 targets, an achievement that some have called ‘the 4th 90’.
Abstract: The availability of potent antiretroviral therapy (ART) has transformed the HIV epidemic, changing HIV disease from a fatal illness to a chronic, manageable condition. In higher income countries, life expectancy for people living with HIV (PLWH) has increased substantially, nearing that of the general population [1–7], and similar gains have been seen in some parts of sub-Saharan Africa, the area of the world most impacted by HIV [2,4,8–12]. Although access to ART is far from universal, substantial progress has been made in reaching the UNAIDS 90– 90–90 targets, that is, that 90% of all PLWH in a community or a country are aware of their status, 90% of those aware have initiated ART, and 90% of those on ART achieve durable viral suppression. [13,14]. The median age of PLWH is expected to increase as the scaleup of HIV treatment continues, with more and more PLWH garnering the survival benefits from treatment. Older adults are also at risk of HIV acquisition and they are rarely prioritized for HIV prevention or testing efforts. The resultant ‘greying of the HIVepidemic’ raises important questions regarding understanding the effect of aging on PLWH, the effect of HIV infection on the aging process, and optimal approaches to HIV prevention among older individuals (Table 1). Thus, a critical priority is to aim for healthy aging among PLWH, an achievement that some have called ‘the 4th 90’.
86 citations
TL;DR: It is found that middle-aged PLWH, when receiving successful treatment, are at increased risk of accelerated aging-related brain changes or cognitive decline over 2 years, and cognitive performance was longitudinally stable in both groups.
Abstract: Background Despite successful antiretroviral therapy, people living with human immunodeficiency virus (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function, and cognitive impairment. This has raised concerns that PLWH may experience accelerated aging-related brain pathology. Methods We performed a multicenter longitudinal study of 134 virologically suppressed PLWH (median age, 56.0 years) and 79 demographically similar human immunodeficiency virus (HIV)–negative controls (median age, 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multimodality neuroimaging (T1-weighted, T2-weighted, diffusion magnetic resonance imaging [MRI], resting-state functional MRI, spectroscopy, arterial spin labeling) at baseline and at 2 years. Group differences in rates of change were assessed using linear mixed effects models. Results One hundred twenty-three PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval, 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking or alcohol use. At baseline, PLWH had poorer global cognitive performance (P .1). Cognitive performance was longitudinally stable in both groups. Conclusions We found no evidence that middle-aged PLWH, when receiving successful treatment, are at increased risk of accelerated aging-related brain changes or cognitive decline over 2 years.
85 citations
Cites background from "Life expectancy of HIV‐positive peo..."
...Combination antiretroviral therapy (cART) has drastically reduced AIDS-associated morbidity and mortality [1], dramatically improving life expectancy for people living with human immunodeficiency virus (PLWH) [2]....
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Pasteur Institute1, Cornell University2, University of KwaZulu-Natal3, Columbia University4, Karolinska Institutet5, University of Cape Town6, Johns Hopkins University7, Geneva College8, Oswaldo Cruz Foundation9, University of New South Wales10, University of Malaya11, University of Toronto12, Women's College Hospital13, Women's College, Kolkata14, University of British Columbia15, Rega Institute for Medical Research16, Universidade Nova de Lisboa17, Joint United Nations Programme on HIV/AIDS18, University of London19
TL;DR: Global prosecutions for non‐disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting, which suggests prosecutions are not always guided by the best available scientific and medical evidence.
Abstract: Introduction Globally, prosecutions for non-disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence. Discussion Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant. Conclusions The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.
84 citations
Cites background from "Life expectancy of HIV‐positive peo..."
...Studies from many countries have consistently shown that antiretroviral therapies have radically increased life expectancy, that life expectancy has continued to improve over time, and that the long-term health and quality of life of people living with HIV has drastically improved [122-141]....
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References
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TL;DR: Moher et al. as mentioned in this paper introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses, which is used in this paper.
Abstract: David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
62,157 citations
TL;DR: Funnel plots, plots of the trials' effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials.
Abstract: Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews . Main outcome measure: Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. Results: In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. Conclusions: A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution. Key messages Systematic reviews of randomised trials are the best strategy for appraising evidence; however, the findings of some meta-analyses were later contradicted by large trials Funnel plots, plots of the trials9 effect estimates against sample size, are skewed and asymmetrical in the presence of publication bias and other biases Funnel plot asymmetry, measured by regression analysis, predicts discordance of results when meta-analyses are compared with single large trials Funnel plot asymmetry was found in 38% of meta-analyses published in leading general medicine journals and in 13% of reviews from the Cochrane Database of Systematic Reviews Critical examination of systematic reviews for publication and related biases should be considered a routine procedure
37,989 citations
TL;DR: A structured summary is provided including, as applicable, background, objectives, data sources, study eligibility criteria, participants, interventions, study appraisal and synthesis methods, results, limitations, conclusions and implications of key findings.
31,379 citations
TL;DR: 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.
1,362 citations
University of British Columbia1, Simon Fraser University2, Johns Hopkins University3, Centers for Disease Control and Prevention4, University of Calgary5, Yale University6, McGill University7, Oregon Health & Science University8, University of California, San Francisco9, University of North Carolina at Chapel Hill10, Vanderbilt University11, Kaiser Permanente12, Harvard University13, University of Washington14, National Institutes of Health15
TL;DR: A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population.
Abstract: Background: Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000–2007 in the U.S. and Canada.
1,182 citations