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People Living With HIV in New York City Still Dying From Infections, Not Just Old Age
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Published on: August 29, 2019
Between 1984 and 1987, the infections accounted for 100% of deaths. Shortly after the introduction of ART, rates dropped in half, with infections accounting for 52% of deaths between 1996 and 1999. Between 2012 and 2016, infections accounted for 86% of deaths.
"Even a HIV-positive patient is immunocompromised and at increased risk of dying from pneumonia," said Rapkiewicz.
https://www.archivesofpathology.org/doi/pdf/10.5858/arpa.2019-0144-OA
https://www.ajmc.com/newsroom/people-living-with-hiv-in-new-york-city-still-dying-from-infection-not-just-old-age
The researchers, who used autopsy reports of 252 people who died of AIDS in New York City between 1984 and 2016, found that infections associated with the virus are still the leading cause of death for the patient population in the state.
A team of researchers has found that while people with HIV are living longer and healthier lives, they are still dying from underlying infection, not just from old age.
Using autopsy reports of 252 people who died of AIDS in New York City between 1984 and 2016, the researchers discovered that infections associated with the virus are still the leading cause of death for the patient population in the state.
Autopsy reports of patients with HIV/AIDS has played a significant role in recognizing the array of infections associated with the virus since the earliest literature of the disease.
"Autopsy reports reliably tell the whole disease story and why people are still dying from it," said Amy Rapkiewicz, MD, associate professor in the Department of Pathology at NYU Langone, vice chair of pathology at NYU Winthrop Hospital, and senior investigator of the study, in a statement. "That is because there is often a difference between the immediately reported cause of death, such as heart attack, and the actual cause of death, whether from obesity, drug use, or HIV/AIDS."
Thanks to the advent of antiretroviral therapy (ART)-introduced in the 1990s-the lifespan of someone living with HIV has increased drastically. According to findings from the study, the average age of death from AIDS in New York City increased from 36 years in 1984 to 54 years in 2010. But the findings also showed that among the 252 people autopsied, pneumocystis pneumonia and other infections still account for the majority of deaths.
Between 1984 and 1987, the infections accounted for 100% of deaths. Shortly after the introduction of ART, rates dropped in half, with infections accounting for 52% of deaths between 1996 and 1999. Between 2012 and 2016, infections accounted for 86% of deaths.
"Even a HIV-positive patient is immunocompromised and at increased risk of dying from pneumonia," said Rapkiewicz.
According to Rapkiewicz, now that people living with HIV are living longer with the virus, other common coinfections, including hepatitis C infections, are beginning to emerge as causes of death. Across the 23-year period, hepatitis C infections were present in 15 patients. Notably, 3 out of the 4 autopsied patients between 2014 and 2016 died from hepatitis C cirrhosis.
One finding that the researchers could not analyze further but said could be explained by future autopsy reports is the increase in atherosclerosis. The condition was observed in 21% of those autopsied between 1988 and 1991. Between 2008 and 2011, the condition was observed in 54%.
Sobia Nizami, MD, a clinical fellow in infectious diseases at NYU Langone, and lead study investigator, said that it's difficult to determine if the finding is a result of people living with HIV living longer, overeating, and following the sedentary lifestyles observed among non-infected people, or if it's a long-term side effect of ART.
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In this study we examined the trends in autopsy dataduring the major epochs of the AIDS epidemic. It waspostulated that an increasing incidence of non–AIDS-related malignancies and cardiovascular disease in HIVpatients at death would emerge in autopsies performed in recent years.
Similar to the previous report20from 1998, an increase in the frequency of non opportunistic bacterial and other infections on autopsy in HIV patients over the years was also found in our study, and this trend continued until 2016. Similar to our findings, CMV has been reported as a frequent finding at autopsy for HIV patients.20 It has been postulated that CMV may have a direct effect on B-cell response and be a cofactor that augments HIV pathogenicity. The association of CMV and AIDS is an evolving topic, and recently Yen et al22reported that CMV was an independent predictor of ischemic stroke in persons living with HIV. A rise in mean age at death at autopsy has been reported20up to 1998. In our study, the age at death increased monotonically between 1984 and 2010 (Figure 2, A). The oldest patient autopsied, at 72 years of age, was seen in1995. The largest mean age at death was seen in the year 2010, 5466 years. However, after 2011 the mean age at death for autopsied patients actually declined to the third or fourth decade of life, and pathologic findings included bacterial infection with hepatitis C cirrhosis. This reflects the fact that despite the overall advances in HIV care, gaps in access to care remained for some younger patients with HIV who were susceptible even in 2016 to liver failure from hepatitis C cirrhosis, sepsis, and death. Based on our experience, we suggest that during this interval autopsies were not pursued as vigorously for older patients with HIV who died with multiple age-related comorbidities.
Trends in Mortality From Human Immunodeficiency VirusInfection, 1984–2016 An Autopsy-Based Study
Sobia Nizami, MD; Cameron Morales, BS; Kelly Hu, BS; Robert Holzman, MD; Amy Rapkiewicz, MD
Context. -With increasing use and efficacy of antiretro-viral therapy for human immunodeficiency virus (HIV)infection, deaths from acquired immunodeficiency syn-drome (AIDS)–defining conditions have decreased.Objective.-To examine trends in the cause of death ofHIV-infected patients who underwent autopsy at a majorNew York City hospital from 1984 to 2016, a periodincluding the major epochs of the AIDS epidemic.
Design.-Retrospective review of autopsy records andcharts with modeling of trends by logistic regression usingpolynomial models.
Results.-We identified 252 autopsies in adult patients with AIDS (by 1982 definition) or HIV infection. Prior to widespread use of highly active antiretroviral therapy, in1984–1995, on average 13 autopsies per year were done. Post–highly active antiretroviral therapy, the average number of autopsies declined to 4.5 per year. The fitted mean age at death was 35 years in 1984 and increased curvilinearly to 46 (95% CI, 43–49) in 2016 (P,.001). By regression analysis, mean CD4þT-cell count increased from 6 in 1992 to 64 in 2016 (P¼.01). The proportion of AIDS-defining opportunistic infections decreased, from79% in 1984–1987 to 41% in 2008–2011 and 29% in2012–2016 (P¼.04). The frequency of non opportunistic infections, however, increased from 37% in 1984–1987 to73% in 2008–2011 and 57% in 2012–2016 (P¼.001). The frequency of AIDS-defining and other malignancies did not change significantly during the study period. The prevalence of atherosclerosis at autopsy rose dramatically, from21% in 1988–1991 to 54% in 2008–2011 (p .001).
Conclusions.-Despite limitations of autopsy studies, many trends in the evolution of the HIV/AIDS epidemicare readily discernable.
Infections
The prevalence of AIDS-defining opportunistic infections decreased during the study period, from 15 among 19 patients (79%) in 1984–1987 to 15 among 37 patients (41%) in 2008–2011 and 2 of 7 patients (29%) in 2012–2016 (Table 3; Figure 4, A). In the last 4-year cohort, no AIDS-defining infections were observed after 2013. The linear trend for these 4-year cohorts over time was statistically significant (P = .03, Mantel-Haenszel v2 for trend = 4.5, df = 1). Overall, 128 autopsies were identified to have AIDS-defining infections. Coinfections from multiple opportunistic pathogens were common. Pneumocystis jirovecii pneumonia (PCP) was the most frequent opportunistic infection, present in 53 autopsies overall, with the highest frequency during 1984–1987 in 10 of 19 patients (53%).
Cytomegalovirus (CMV) infection was the second most common infection, found in 47 autopsies during the study period. The probabilities of PCP, CMV, and Cryptococcus infections decreased during the study period, and Mycobacterium avium complex disease infections among autopsies were sporadic and remained fairly constant over the years. These probabilities were assessed by polynomial regression as shown in Figure 5, A through D.
In contrast to the decline in AIDS-defining infections, the frequency of non–AIDS-defining infections increased during the study period, from 7 of 19 patients (37%) in 1984–1987 to 27 of 37 (73%) in 2008–2011 and 4 of 7 (57%) in 2012–2016 (P = .001, df = 1) (Figure 4, B). These infections included bacteremia, endocarditis, pneumonia, Mycobacterium tuberculosis, hepatitis C, and Clostridium difficile, with nearly all patients having coinfections.
We also assessed the overall prevalence of infections as a direct cause of death, including both opportunistic and nonopportunistic infections, and excluding patients with trauma or other predominant factors leading to death. This frequency was very high in the initial study years-100% during 1984–1987. It declined during the next decade to a nadir of 11 of 21 cases (52%) by 1996–1999, and then increased again, as shown with logistic regression analysis in Figure 4, C.
Hepatitis C infections occurred in a total of 15 of the 252 patients. These were distributed sporadically, although notably 3 out of 4 autopsied patients in 2014–2016 died from hepatitis C cirrhosis.
Jaime Rosenberg
Reference
Nizami S, Morales C, Hu K, Holzman R, Rapkiewicz A. Trends in mortality from human immunodeficiency virus infection, 1984-2016: an autopsy-based study [published online August 28, 2019]. Arch Pathol Lab Med. doi:10.5858/arpa.2019-0144-OA.
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