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Closing the Gap: Increases in Life Expectancy
among Treated HIV-Positive Individuals in the United States and Canada
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article excerpts below
PLOS one published Dec 18 2013
Hasina Samji1, Angela Cescon1, Robert S. Hogg1,2*, Sharada P. Modur3, Keri N. Althoff3, Kate Buchacz4,
Ann N. Burchell5, Mardge Cohen6, Kelly A. Gebo3, M. John Gill7, Amy Justice8, Gregory Kirk3,
Marina B. Klein9, P. Todd Korthuis10, Jeff Martin11, Sonia Napravnik12, Sean B. Rourke5,
Timothy R. Sterling13, Michael J. Silverberg14, Stephen Deeks15, Lisa P. Jacobson3, Ronald J. Bosch16, Mari M. Kitahata17, James J. Goedert18, Richard Moore3, Stephen J. Gange3, for The North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of IeDEA"
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Life Expectancy for North Americans with HIV Reaches Historic High
Healthine.com Written by David Heitz | Published on December 18, 2013
"[It is] nothing short of miraculous, given where we were 20 years ago," said Dr. Mark Smith, who treats people with HIV and also serves as president of the California HealthCare Foundation. "It's a stunning success story for biomedical science and has contributed greatly to our understanding of other viruses and disease processes as well."
The study looked at 23,000 HIV patients in the United States and Canada from 2002 to 2007. Subjects came from a wide range of racial and socioeconomic backgrounds. Intravenous drug users and non-white patients fared the worst, see tables from study below.
Kyle Murphy, assistant director of communications for the National Minority AIDS Council, called the disparity in life expectancy between whites and non-whites with HIV "very real and devastating."
"Across the board, communities of color fare worse than their white counterparts," he told Healthline. "They are diagnosed much later and are less likely to be retained in care or to be virally suppressed."
Dr. Joel Gallant, chair of the HIV Medicine Association, told Healthline he does not believe that race is an independent factor affecting life expectancy. "It's a proxy for more infections from drug use and later presentation to care," he said.
The gay demographic, he said, tends to get tested for HIV regularly and to begin antiretroviral drugs immediately. Gallant, who said he sees HIV patients even in their eighties, noted that more people are being diagnosed at a later age, in part because older people tend not to get tested as often.
Early detection and treatment can now mean a normal lifespan for otherwise healthy Americans. The study results show that people who begin taking antiretroviral drugs earlier live longer. By lowering the number of viral cells in the blood, antiretroviral therapy, or ART, also helps to prevent HIV transmission.
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Closing the Gap: Increases in Life Expectancy among Treated HIV-Positive Individuals in the United States and Canada
PLOS one Dec 18 2013
"Based on current patterns of ART use among participants observed from 2000 to 2007 in the NA-ACCORD, a 20-year-old individual on ART today in the U.S. or Canada would expect to live into their early 70 s, a life expectancy that approaches that of a 20-year-old person in the general population [12]. Life expectancy estimates for the general population at age 20 years in 2009 were 59.7 and 57.0 years for men and 63.9 and 61.7 years for women, in Canada and the U.S., respectively [12]. Indeed, given that many individuals living with HIV have demographic, clinical, and behavioral characteristics associated with greater morbidity and mortality than the general population [20], [21], the gap in life expectancy may be attributable to other lifestyle factors and not just HIV infection."
Differences in life expectancy by race were also evident, with white individuals having higher life expectancies in all periods. As with persons with a history of IDU, these differences in life expectancy may be reflective of underlying differences in socioeconomic conditions, access to care, and health insurance coverage, suggesting an urgent need for strategies and programs to combat these inequities [28], [29]. However, we note that the gap in life expectancy between white and non-white individuals has decreased substantially, from 23.0 years in 2000-02 to 8.5 years in 2006-07.
Additional differences in life expectancies were noted by CD4 cell count at ART initiation in all periods. These findings may lend additional support to the earlier initiation of ART, in accordance with both the DHHS guidelines recommending universal therapy [30] and the 2012 International AIDS Society-USA (IAS-USA) guidelines, which recommend use of ART for all HIV-positive individuals regardless of CD4 cell count, except in the case of long-term non-progressors and elite controllers [3]. While our sample size limited our ability to analyze differences in life expectancy by more than two CD4 cell count strata, further analyses examining life expectancies for individuals starting ART with CD4 counts >500/mm3 would be beneficial.
Results
Our study population consisted of 22,937 treatment-naive ART initiators age ³20 years. Participants contributed 82,022 person-years and 1,622 deaths for an overall unweighted (i.e., without accounting for censoring weights) mortality rate of 19.8 [95% Confidence Interval (CI): 18.8, 20.8] per 1,000 person-years. In a sensitivity analysis restricted to only those who were observed to initiate ART during our study period (18,591 participants contributing 1,057 deaths), the overall unweighted mortality rate was 18.9 (95% CI: 17.8, 20.1) per 1,000 person-years.
Table 1 describes the demographic characteristics of included participants, overall and by calendar period. As individuals can contribute person-time to a number of periods, these calendar periods are not mutually exclusive. Of the entire sample, 77% were male, 20% had a history of IDU, 62% were non-white, and 72% initiated ART with a CD4 cell count <350 cells/mm3. Other than age, demographic and clinical characteristics remained stable across periods.
Table 2 characterizes the study sample in terms of number of deaths and unweighted mortality rates (per 1,000 person-years). In general, mortality rates were highest among individuals with IDU history (34.5, 95% CI: 31.9, 37.4) compared with MSM and other transmission groups, non-whites (22.4, 95% CI: 21.1, 23.8) compared with whites, and individuals with CD4 counts <350 cells/mm3 (23.3, 95% CI: 22.1, 24.6) compared with those with CD4 ³350 cells/mm3.
Figure 1 shows unweighted age-specific mortality rates for the three periods under observation. As expected, age-specific mortality rates were highest in the earliest period and lowest in the most recent period. In a sensitivity analysis, we estimated mortality rates in fourteen participating cohorts that collect information about deaths by linking to death registries to four that do not; although we see a slightly higher mortality rate among cohorts with death registry matches, the impact on life expectancy estimates appears minimal (data not shown) (see Appendix S3 for more information).
Table 3 presents overall life expectancy estimates based on unweighted mortality rates and mortality rates weighted for loss to follow-up. The unweighted and weighted life expectancy estimates were similar, with overall life expectancy estimates of 42.6 and 42.7 years, respectively; however the standard error was slightly larger when the unweighted mortality rates were used (SE 0.2 vs. SE 0.1). Over the entire study period, women had similar life expectancies to men, IDUs had lower life expectancies than MSM and individuals with other risk factors, non-whites had lower life expectancies than whites, and those with CD4 count <350 cells/mm3 had a lower life expectancy than those with CD4 count ³350 cells/mm3. Finally, in a sensitivity analysis (further described in Appendix S4), when the sample was restricted to those who initiated therapy after 2000, life expectancy at 20 years increased to 45.1 years (SE 0.3).
Table 4 and Figure 2 show life expectancy at age 20 years by calendar period and by sociodemographic characteristics based on unweighted mortality rates. Life expectancy at age 20 years increased with calendar time, from 36.1 (SE 0.5) years in 2000-2002 to 51.4 (SE 0.5) years in 2006-2007. There was an increase in life expectancy among all groups over calendar time with the exception of individuals with a history of IDU, who had the lowest recorded life expectancies in all periods.
Discussion
Based on current patterns of ART use among participants observed from 2000 to 2007 in the NA-ACCORD, a 20-year-old individual on ART today in the U.S. or Canada would expect to live into their early 70 s, a life expectancy that approaches that of a 20-year-old person in the general population [12]. Life expectancy estimates for the general population at age 20 years in 2009 were 59.7 and 57.0 years for men and 63.9 and 61.7 years for women, in Canada and the U.S., respectively [12]. Indeed, given that many individuals living with HIV have demographic, clinical, and behavioral characteristics associated with greater morbidity and mortality than the general population [20], [21], the gap in life expectancy may be attributable to other lifestyle factors and not just HIV infection.
Importantly, our results are not confounded by previous antiretroviral use, as all participants were treatment-naive before initiating combination therapy. Weighted and unweighted rates overall and by calendar period produced similar results suggesting that our adjusted estimates are robust to any potential for informative censoring bias from the variables that were included in our model. Life expectancy does differ markedly by transmission group, race, and CD4 cell count at ART initiation; in particular, it is notably lower in individuals with a history of IDU, who are non-white, and who began ART with lower CD4 cell counts.
In the early years of ART availability, mortality was highest in the first year after ART initiation, but this has decreased over time. The modern ART era, in which mortality has become increasingly dependent on duration of ART, is characterized by a greater proportion of patients with longer follow-up. Therefore, the increase in life expectancy in the more recent time periods may reflect both a lower mortality rate in patients initiating ART and the mortality in those with a longer duration of ART use.
Our results are consistent with previous studies that have examined the life expectancy of HIV-positive individuals on ART [22]. While prior studies have observed similar decreases in mortality and increases in life expectancy among HIV-positive individuals as a result of ART [23], such findings have often been localized at the provincial or state level, and may now be less relevant to the current context of antiretroviral care [24], [25]. Furthermore, this is the first study to examine life expectancy in such a large sample of heterogeneous HIV-positive individuals on ART across the U.S. and Canada, and therefore provides novel data from this region.
The absence of significant differences in life expectancy by sex, and the higher life expectancy of men in the latest period suggests that there is in fact a sex differential in life expectancy in our study. In general, in high-income countries such as the U.S. and Canada we expect women to have higher life expectancies than men, which was not evident in our findings [12]. Similar life expectancies by sex or higher life expectancy for men suggest that women may be accessing HIV-related care at later stages of HIV disease than men in Canada and the U.S., which has significant public health ramifications. The sex differential, noted here, may also be explained in part due to the fact that general population comparisons better represent all men and women, while HIV-positive men here are weighted towards MSM and women toward IDU. Variation in levels of education and income, as well as access to the health care system, social stigma, and marginalization are other factors that may influence the observed differences by sex [26].
There are also considerable differences in life expectancy by HIV transmission group, with lower life expectancies reported in all periods for individuals with a history of IDU. This finding is consistent with previous findings from the ART Cohort Collaboration (a multisite cohort collaboration that includes seven sites in North America) and work done in British Columbia, Canada [2], [27]. We hypothesize a number of possible reasons for these differences, including increased comorbidity with greater non-AIDS related mortality, as well as challenges with ART adherence, active drug use, hepatitis C co-infection, housing instability, and lower socioeconomic status. Our findings here clearly illustrate that individuals with IDU history have not seen the increases in life expectancy that are evident in other groups.
Differences in life expectancy by race were also evident, with white individuals having higher life expectancies in all periods. As with persons with a history of IDU, these differences in life expectancy may be reflective of underlying differences in socioeconomic conditions, access to care, and health insurance coverage, suggesting an urgent need for strategies and programs to combat these inequities [28], [29]. However, we note that the gap in life expectancy between white and non-white individuals has decreased substantially, from 23.0 years in 2000-02 to 8.5 years in 2006-07.
Additional differences in life expectancies were noted by CD4 cell count at ART initiation in all periods. These findings may lend additional support to the earlier initiation of ART, in accordance with both the DHHS guidelines recommending universal therapy [30] and the 2012 International AIDS Society-USA (IAS-USA) guidelines, which recommend use of ART for all HIV-positive individuals regardless of CD4 cell count, except in the case of long-term non-progressors and elite controllers [3]. While our sample size limited our ability to analyze differences in life expectancy by more than two CD4 cell count strata, further analyses examining life expectancies for individuals starting ART with CD4 counts >500/mm3 would be beneficial.
In reviewing these findings, there are several potential limitations that readers of our work should consider. A caveat of life expectancy analyses in general is that they may underestimate more recent improvements in extending life since age-specific mortality rates are based on a given point in time and assumed to apply for the duration of an individual's life [22]. Also, our results can only be generalized to those newly initiating ART, and not those with previous exposure to antiretroviral therapy. Although this collaboration includes the largest number of HIV-positive individuals and broadest geographic distribution in the U.S and Canada analyzed to-date, these individuals may not be fully representative of the epidemic in the entire region. However, previous analyses of the NA-ACCORD indicate that it does represent the demography of the epidemic in the U.S. [31]. Next, cohorts in this collaboration may under-represent those at greatest risk of death, as such individuals are less likely to seek care or to remain under care at one clinic. Thus, cohorts that did not link to vital statistics may miss deaths that occurred outside of the clinic setting. However, most participants (88%) were from cohorts that did link to vital statistics data. To further investigate this issue, we conducted sensitivity analyses taking into account loss to follow-up, and were reassured to find little differences in our estimates. Variations due to small numbers may also affect our estimates, especially due to the truncation of age intervals at older ages and the small number of deaths observed for some time intervals. We addressed the impact of small numbers by smoothing rates and examining the distribution of deaths over a calendar period. Finally, due to the increased risk of age-related co-morbidities among HIV-positive adults, it is possible life expectancy may plateau or decrease in the future; it will be important to monitor life expectancy estimates as more adults age with HIV.
In conclusion, the results of this study document increasing longevity for individuals living with HIV in the U.S. and Canada. The marked increase in life expectancy at age 20 from 36.1 years in 2000-2002 to 51.4 years in 2006-2007 is a testament to the improvements and overall success of ART. However, large differences in life expectancy persist between certain sub-groups of patients. Future work should consider specific reasons for these life expectancy gains, overall and within each sub-group. These data will be vital to target priorities for improvements in health services. Finally, in addition to quantity, future work should consider quality of life, as the proportion of individuals aging with HIV continues to grow.
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