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"study documented extremely elevated risks of death for non-ADCs among PWA"....Non-AIDS Defining Cancer Mortality: Emerging Patterns in the Late HAART Era....."our results call for taking primary and
secondary preventive actions to reduce both cancer incidence and mortality among people with HIV or AIDS."
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Download the PDF here
from Jules: the study reported below following these links finds 7-fold increased risk for cancers in people who have had AIDS and rates among HIV+ are higher vs HIV-neg among younger than 55 & older than 55 to 74. Here are some links to relevant studies, one published last eek that HIV+ are less likely to have cancer treatment & care....exercise & diet are the best preventive medicines to prevent cancers in addition to successful HAART with high CD4 & undetectable oral load, the higher the CD4 the better, CD4 above 1000 is better than 750 which is better than 500 which is better than 350.
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"The growing burden of non-AIDS-defining cancers highlights the need for cancer prevention and early detection among HIV-infected people......HIV-infected women should be screened for cervical cancer according to specific guidelines (36)"
Disparities in cancer treatment among patients infected with the human immunodeficiency virus - HIV Patients Less Likely To Have Cancer Treatments, Study Says - (05/23/16)
Lifestyle improvements: exercise [diet]: Preventable Incidence and Mortality of Carcinoma Associated With Lifestyle Factors Among White Adults in the United States - (05/23/16)
Higher Non-AIDS Cancer Rate in Men With HIV: 30-Year MACS
Study .......http://www.natap.org/2015/AGE/AGE_04.htm .......Men with HIV had significantly higher incidence of virus-related non-AIDS cancers than men without HIV, both among men younger than 55 (incidence rate ratio [IRR] 7.2, 95% confidence interval [CI] 3.4 to 15.2) and men 55 or older (IRR 2.7, 95% CI 1.1 to 6.6). Younger and older men with HIV also had higher rates of nonviral cancers (IRR 1.8, 95% CI 1.3 to 2.6, for younger men; IRR 1.3, 95% CI 0.9 to 1.9, for older men).
HIV Keeps Evolving in Cancer Tissues and Other Tissues During Suppressive
ART ......http://www.natap.org/2016/CROI/croi_28.htm....Antiretroviral therapy (ART) that controlled HIV replication in plasma and often cerebrospinal fluid (CSF) did not slow viral evolution in cancer tissues and other pathologic tissues, according to results of autopsy studies by Michael McGrath (University of California, San Francisco) and colleagues at other sites [1]. They proposed that HIV-infected macrophages may carry virus to these tissue sanctuaries......McGrath and colleagues noted that lymphatic tissue, tumor tissue, and brain tissue in these patients "are sites of replicating virus as evidenced by RNA sequences and mRNA expression of gag-pol and thus may serve as a [viral] sanctuary."
Cancer Burden in the HIV-Infected Population in the United States: Anal & Cervical Cancers Increased -Natl Cancer Institute/NIH Report....http://www.natap.org/2015/HIV/101915_01.htm........"As the HIV-infected population in the United States continues to grow and age, cancer will emerge as an important public health issue........the burden of non-AIDS-defining cancers has grown among HIV-infected people in the United States
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"study documented extremely elevated risks of death for non-ADCs among PWA"....Non-AIDS Defining Cancer Mortality: Emerging Patterns in the Late HAART Era......this nationwide population-based study aimed to assess
excess risk of cancer-related deaths among Italian PWA, as compared to people without AIDS.....It is worth remembering that our data included only HIV-infected individuals having already had an AIDS diagnosis. Thus, study results cannot be referred to HIV-infected people at an earlier stage of immunodeficiency. In particular, given that AIDS diagnosis can be a consequence of the diagnosis of an ADC, SMRs for ADCs could be much lower in the case of HIV-infected people without AIDS (in our data, approximately 84% of PWA reporting ADCs at death reported also ADCs at diagnosis).....study findings stress the need of monitoring the burden of both virus-related and non virus-related cancers among PWA in the late HAART era, as they are at still at a higher risk of death than the HIV-negative population.
....(non-PWA), in the late HAART era......This study provided nationwide, population-based estimates of the excess cancer mortality among Italian PWA, as compared to people without HIV/AIDS, in the late-HAART era. In addition to extremely elevated risks of death for ADCs, the study documented a statistically significant higher mortality also for cancers not directly associated with HIV/AIDS, with an overall 7.3-fold excess risk for all non-ADCs combined. This latter figure can be interpreted as a combination of the increased incidence of such malignancies15,19-22 and of the reduced cancer survival of people with HIV/AIDS.16,23,24......Overall, significant excess mortality emerged for cancers associated with viruses, for which HIV-infected individuals are likely to lose the immune control of infections, and for cancers associated to unhealthy behaviors, like tobacco smoking. All these risk factors have been shown to be more common among HIV-infected individuals than among uninfected ones.1,4,5,25,26 Furthermore, mortality in HIV patients without such risk factors was found to be very similar to that of the non-HIV-infected individuals in a Danish cohort.26 In particular, the poorer survival observed among HIV-infected people via IDU was recently reported to be mostly due to HCV co-infection.27 In our study, PWA infected via IDU reported also very high SMRs.
In conclusion, study findings stress the need of monitoring the burden of both virus-related
and non virus-related cancers among PWA in the late HAART era, as they are at still
at a higher risk of death than the HIV-negative population. This applies in particular to PWA
who acquired HIV infection through IDU. Indeed, our results call for taking primary and
secondary preventive actions to reduce both cancer incidence and mortality among people
with HIV or AIDS.
Table 2 shows the distribution of malignant neoplasms reported in death certificates of
PWA and non-PWA, using MCoD data. AIDS-defining cancers (ADCs) were reported in
22.9% of death certificates of PWA: non-Hodgkin lymphoma in 18.0%, Kaposi sarcoma in
5.1%, and cervical cancer in 2.5%. Similar figures were found among PWA aged 15-49 and
50-74 years, with the exception of no mention of cervical cancer among female PWA aged
50 years or more. Conversely, these same malignancies were rarely reported as causes of
death in non-PWA (<2% of total deaths, in all age groups).
Both PWA infected trough IDU or through sexual intercourses reported extremely
elevated excess mortality for ADCs (Table 4)
Considering PWA infected through sexual intercourses, the SMR for non-ADCs overall
was 4.9 (95% CI: 3.8-6.2). Very high SMRs emerged especially for anal cancer
(SMR=189.5; 95% CI: 39.1-553.9), Hodgkin lymphoma (SMR=115.9; 95% CI:
50.0-228.4), but significant excess mortality was detected also for leukemias (SMR=8.2;
95% CI: 2.2-21.0), lung (SMR=5.1; 95% CI: 3.1-8.0), and colorectal cancer (SMR=3.5; 95%
CI: 1.1-8.3)
Excess mortality, as compared to non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs).....SMRs were calculated as the ratio between the observed number of deceased PWA who had a specific cancer to the expected one, estimated on the basis of sex- and age-specific (quinquennia) mortality rates among non-PWA, multiplied by the person-years at risk among PWA.
Tables 3 and 4 show the observed and the expected numbers of cancer-related deaths with
the corresponding SMRs, overall and in selected sub-groups. ADCs, in particular Kaposi
sarcoma, showed extremely high excess mortality, especially among PWA younger than 50
years (Table 3). When considering all non-ADCs together, a 7.3-fold excess risk of death was
observed (95% CI: 6.1-8.7) with a higher excess in the youngest group of PWA (SMR=14.2,
95% CI: 10.8-18.5, for 15-49 years vs. 5.3, 95% CI 4.1-6.7, for 50-74 years). Remarkably
elevated excess risks of death emerged for anal cancer (SMR=228) and Hodgkin lymphoma
(SMR=122). Statistically significant excess mortality was also found for not otherwise
specified uterine cancers (SMR=52.5, 95% CI: 14.3-135), liver (SMR=13.2, 95% CI:
7.7-21.1), skin melanoma (SMR=10.9, 95% CI: 3.0-27.8), lung (SMR=8.0, 95% CI:
5.7-11.0), head and neck (SMR=7.8, 95% CI: 3.6-14.9), leukemia (SMR=7.6, 95% CI:
2.4-17.7), and colon-rectum (SMR=5.4, 95% CI: 2.6-10.0).
Female PWA reported higher
excess mortality than males for non-Hodgkin lymphoma (SMR=339, 95% CI: 292-392, in
men; SMR=554, 95% CI: 386-771 in women) and lung cancer (SMR=7.4, 95% CI: 5.1-10.4
in men; SMR=17.3, 95% CI: 5.6-40.3 in women).
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Non-AIDS Defining Cancer Mortality: Emerging Patterns in the Late HAART Era.
JAIDS April 21 2016
Zucchetto, Antonella Ph.D.; Virdone, Saverio Sc.D.; Taborelli, Martina Sc.D.; Grande, Enrico Sc.D.; Camoni, Laura Psy.D; Pappagallo, Marilena Sc.D.; Regine, Vincenza Sc.D.; Grippo, Francesco Sc.D.; Polesel, Jerry Sc.D.; Dal Maso, Luigino Ph.D.; Suligoi, Barbara M.D.; Frova, Luisa Ph.D.; Serraino, Diego M.D.
Abstract
Background. Non-AIDS defining cancers (non-ADCs) have become the leading non-AIDS-related cause of death among people with HIV/AIDS. We aimed to quantify the excess risk of cancer-related deaths among Italian people with AIDS (PWA), as compared to people without AIDS (non-PWA).
Methods. A nationwide, population-based, retrospective cohort study was carried out among 5285 Italian PWA, aged 15-74 years, diagnosed between 2006 and 2011. Date of death and multiple-cause-of-death (MCoD) data were retrieved up to December 2011.Excess mortality, as compared to non-PWA, was estimated using sex- and age-standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs).
Results.
Among 1229 deceased PWA, 10.3% reported non-ADCs in the death certificate, including lung (3.1%) and liver (1.4%) cancers.
A 7.3-fold (95% CI: 6.1-8.7) excess mortality was observed for all non-ADCs combined.
Statistically significant SMRs emerged for specific non-ADCs, i.e., anus (5 deaths, SMR=227.6, 95% CI: 73.9-531.0), Hodgkin lymphoma (12 deaths, SMR=122.0, 95% CI: 63.0-213.0), unspecified uterus (4 deaths, SMR=52.5, 95% CI: 14.3-135.0, liver (17 deaths, SMR=13.2, 95% CI: 7.7-21.1), skin melanoma (4 deaths, SMR=10.9, 95% CI: 3.0-27.8), lung (38 deaths, SMR=8.0, 95% CI: 5.7-11.0), head and neck (9 deaths, SMR=7.8, 95% CI: 3.6-14.9), leukemia (5 deaths, SMR=7.6, 95% CI: 2.4-17.7), and colon-rectum (10 deaths, SMR=5.4, 95% CI: 2.6-10.0). SMRs for non-ADCs were particularly elevated among PWA infected through injecting drug use.
Conclusion. This population-based study documented extremely elevated risks of death for non-ADCs among PWA. These findings stress the need of preventive interventions for both virus-related and non virus-related cancers among HIV-infected individuals.
Introduction
The increasing survival of HIV-infected individuals with access to highly active
antiretroviral therapy (HAART) has led to dramatic changes in mortality patterns of people
with HIV/AIDS.1,2 While mortality rates for AIDS-related conditions have been decreasing
over time, those of non-AIDS-related ones remained unchanged or decreased very slightly.3-5
In particular, non-AIDS defining cancers (non-ADCs, i.e., cancers other than Kaposi sarcoma,
non-Hodgkin lymphoma, and cervix uteri) have become the leading non-AIDS-related causes
of death in the late HAART era, among both people with HIV1,3 and people with AIDS
(PWA).6
Nonetheless, the risk of death as compared to the HIV-uninfected population is still far
from being assessed for each cancer site/type in the late HAART era, as only few studies
quantified excess mortality for specific cancers among people with HIV4 or PWA.6 In
addition, most mortality studies were solely based on the underlying cause of death (i.e., the
disease or injury which initiated the train of morbid events leading directly to death),7 which
is poorly informative of the complexity of the morbidity conditions that affect people with
HIV/AIDS. Furthermore, such approach does not allow a direct comparison with the
uninfected population because most death certificates of people with HIV/AIDS report
'HIV/AIDS' as the underlying cause of death.6,8 To overcome such limits, several methods
have been used.3-6,8,9 For instance, in a previous Italian investigation aimed at quantifying the
excess cancer mortality among PWA, as compared to the general population, we re-assigned
the underlying cause of death by excluding HIV/AIDS reference in the death certificates.10,11
Currently, the availability in Italy of multiple-cause-of-death (MCoD) data (i.e., all the
conditions reported in death certificates -beyond the underlying cause of death) allows
making a direct comparison of the death certificates of people with HIV/AIDS with those of
people without. Furthermore, it allows investigating in detail the presence at death of specific
cancer sites/types and other diseases even if these conditions were not selected as the
underlying cause. Using MCoD data, this nationwide population-based study aimed to assess
excess risk of cancer-related deaths among Italian PWA, as compared to people without AIDS
(non-PWA), in the late HAART era.
Methods
This retrospective cohort study is part of a larger epidemiological, population-based,
nationwide investigation on the survival and mortality patterns of PWA in Italy.12 The
following data sources were used: 1) the National AIDS Registry (RAIDS) at the National
Health Institute (ISS), which collects mandatory data on all people newly diagnosed with
AIDS (according to the 1993 revised European definition13); 2) the National Register of
Causes of Death (RCoD) at the National Institute of Statistics (ISTAT) which collects all
death certificates mandatorily issued in Italy.14 MCoD data are coded by RCoD, according to
the International Classification of Diseases 10th revision, ICD-10 rules and provisions issued
by the World Health Organization.7
In order to compare causes of death between PWA and non-PWA, RAIDS and RCoD data
were linked for the concurrently available period, i.e., 2006-2011. The record-linkage
procedure was conducted in observance of current laws regulating the use of RAIDS and
RCoD data (i.e., inclusion of the investigation in the Italian National Statistical Plan
according to permission of the Data Protection Authority).12 The record-linkage procedure
was carried out by means of a validated, semi-automated, software application using names,
surnames, and dates of birth that were blinded to the operator and removed from the
output.15,16 In order to guarantee the highest completeness of the record-linkage procedure, we
excluded: (a) PWA who were residing in the provinces of Trento and Bolzano, because their
names were not available in RCoD; and (b) PWA who were foreign citizens, because of
possible bias deriving by a higher frequency of spelling errors in their names when recorded
at RAIDS and by a higher propensity of these people to migrate abroad and of being lost to
follow-up.
For the aims of this study, 'PWA deaths' were identified by linked records in RAIDS and
RCoD, whereas 'non-PWA deaths' were identified by RCoD records not linked with RAIDS.
Furthermore, in order to avoid the inclusion of HIV-infected people in the comparison group,
we excluded from the 'non-PWA deaths' category those records reporting AIDS/HIV-related
conditions (i.e., ICD-10 codes B20-B24).
To improve comparability between the study groups, the present analysis was restricted to
PWA aged 15 to 74 years at diagnosis or at death. Furthermore, we excluded PWA with less
than 1 month of follow-up, as the day (within the date) of AIDS diagnosis was often missing;
this selection allowed also the exclusion of those PWA diagnosed at death. Our analysis
finally included 1229 deaths occurred among 5285 PWA, and 952,019 non-PWA deaths.
Person-years at risk of death for PWA were calculated from the date of AIDS diagnosis to
the date of death, or to December 31st, 2011, whichever came first. PWA who had been
diagnosed within 74 years of age but who died thereafter were censored at their 75th birthday.
The risk of death of PWA, as compared to non-PWA, was estimated using sex-and agestandardized
mortality ratios (SMRs).17
SMRs were calculated as the ratio between the observed number of deceased PWA who
had a specific cancer to the expected one, estimated
on the basis of sex- and age-specific (quinquennia) mortality rates among non-PWA,
multiplied by the person-years at risk among PWA. Mortality rates for non-PWA were
computed using, as numerator, the observed number of deceased non-PWA for that specific
condition, and, as denominator the average resident Italian population of same sex and age in
the study period (after the exclusion of Trento and Bolzano provinces, and foreign citizens),
as a proxy of person years at risk of death. Corresponding 95% confidence intervals (CIs)
were computed using the exact Poisson method as appropriate for rare events (i.e., ≤5).18
However, cancer sites with a total number of observed deaths below 4 were reported in the
auxiliary Table A (see Supplemental Digital Content, http://links.lww.com/QAI/A820).
Secondary malignancies and malignant neoplasms not otherwise specified (i.e., ICD-10
codes: C77-C80) were not considered in these analyses, as they were almost always (except
in 8 cases out of 141 PWA deaths) reported in death certificates together with defined cancers
and were, therefore, not relevant for the study aim.
Results
Table 1 shows the distribution of 5285 Italian PWA diagnosed during 2006-2011, and of
the 1229 deceased who had died as of 31st December 2011, according to main characteristics
at AIDS diagnosis. Mean follow-up time was 2.5 years, for a total of 14,180 person-years at
risk of death. The proportion of observed deaths among PWA increased with age at AIDS
diagnosis, whereas it decreased with increasing years of education; moreover, it was
particularly high among PWA infected through injecting drug use (IDU) (31%), and it was
the lowest among homosexual PWA (17%).
Table 2 shows the distribution of malignant neoplasms reported in death certificates of
PWA and non-PWA, using MCoD data. AIDS-defining cancers (ADCs) were reported in
22.9% of death certificates of PWA: non-Hodgkin lymphoma in 18.0%, Kaposi sarcoma in
5.1%, and cervical cancer in 2.5%. Similar figures were found among PWA aged 15-49 and
50-74 years, with the exception of no mention of cervical cancer among female PWA aged
50 years or more. Conversely, these same malignancies were rarely reported as causes of
death in non-PWA (<2% of total deaths, in all age groups).
Non-ADCs were reported in 10.3% of total deaths among PWA. The most frequent type
was lung cancer (in 3.1% of death certificate, 38 deaths), followed by liver cancer (1.4%, 17
deaths), Hodgkin lymphoma (1.0%, 12 deaths). Among female PWA, unspecified uterine
cancer was reported in 1.7% of death certificates (4 cases). Non-ADCs were more frequently
observed in PWA who died between the ages of 50 and 74 years (13.8% of death certificates)
than in younger ones (7.9%). As expected, non-ADCs were by far more frequently observed
among non-PWA (46.8% of death certificates).
Tables 3 and 4 show the observed and the expected numbers of cancer-related deaths with
the corresponding SMRs, overall and in selected sub-groups. ADCs, in particular Kaposi
sarcoma, showed extremely high excess mortality, especially among PWA younger than 50
years (Table 3). When considering all non-ADCs together, a 7.3-fold excess risk of death was
observed (95% CI: 6.1-8.7) with a higher excess in the youngest group of PWA (SMR=14.2,
95% CI: 10.8-18.5, for 15-49 years vs. 5.3, 95% CI 4.1-6.7, for 50-74 years). Remarkably
elevated excess risks of death emerged for anal cancer (SMR=228) and Hodgkin lymphoma
(SMR=122). Statistically significant excess mortality was also found for not otherwise
specified uterine cancers (SMR=52.5, 95% CI: 14.3-135), liver (SMR=13.2, 95% CI:
7.7-21.1), skin melanoma (SMR=10.9, 95% CI: 3.0-27.8), lung (SMR=8.0, 95% CI:
5.7-11.0), head and neck (SMR=7.8, 95% CI: 3.6-14.9), leukemia (SMR=7.6, 95% CI:
2.4-17.7), and colon-rectum (SMR=5.4, 95% CI: 2.6-10.0).
The SMRs were generally higher in the 15-49-years age group (Table 3). In particular, elevated excess risks among
younger PWA emerged for liver (SMR=38.8 among PWA who died at ages 15-49 years vs.
SMR=7.6 at ages 50-74 years) and lung cancers (SMR=22.0 and 5.7, respectively). The sex
stratified analysis (see Table B, Supplemental Digital Content,
http://links.lww.com/QAI/A820) showed similar SMRs for both ADCs (SMR=424, 95% CI:
372-482, in men; SMR=487, 95% CI: 358-647 in women) and non-ADCs (SMR=7.1, 95%
CI: 5.8-8.6, in men; SMR=9.1, 95% CI: 5.6-14.1 in women). Female PWA reported higher
excess mortality than males for non-Hodgkin lymphoma (SMR=339, 95% CI: 292-392, in
men; SMR=554, 95% CI: 386-771 in women) and lung cancer (SMR=7.4, 95% CI: 5.1-10.4
in men; SMR=17.3, 95% CI: 5.6-40.3 in women).
Both PWA infected trough IDU or through sexual intercourses reported extremely
elevated excess mortality for ADCs (Table 4). PWA who had been infected through IDU
showed particularly high excess mortality for non-ADCs, being the overall SMR equal to
20.0 (95% CI: 15.1-26.1). Of note, 14 out of 17 (82%) liver cancers occurred among IDU
PWA, corresponding to a SMR of 74.7 (95% CI: 40.8-125.3). Also the SMRs of anus
(SMR=440.4, 95% CI: 53.3-1591), not otherwise specified uterus (SMR=156.8, 95% CI
32.3-458.2), lung (SMR=29.3, 95% CI: 17.4-46.3), and head and neck cancers (SMR=23.6;
95% CI: 7.6-55.0) were extremely elevated in this group.
Considering PWA infected through sexual intercourses, the SMR for non-ADCs overall
was 4.9 (95% CI: 3.8-6.2). Very high SMRs emerged especially for anal cancer
(SMR=189.5; 95% CI: 39.1-553.9), Hodgkin lymphoma (SMR=115.9; 95% CI:
50.0-228.4), but significant excess mortality was detected also for leukemias (SMR=8.2;
95% CI: 2.2-21.0), lung (SMR=5.1; 95% CI: 3.1-8.0), and colorectal cancer (SMR=3.5; 95%
CI: 1.1-8.3).
Discussion
This study provided nationwide, population-based estimates of the excess cancer
mortality among Italian PWA, as compared to people without HIV/AIDS, in the late-HAART
era. In addition to extremely elevated risks of death for ADCs, the study documented a
statistically significant higher mortality also for cancers not directly associated with
HIV/AIDS, with an overall 7.3-fold excess risk for all non-ADCs combined. This latter figure
can be interpreted as a combination of the increased incidence of such malignancies15,19-22
and of the reduced cancer survival of people with HIV/AIDS.16,23,24
Overall, significant excess mortality emerged for cancers associated with viruses, for
which HIV-infected individuals are likely to lose the immune control of infections, and for
cancers associated to unhealthy behaviors, like tobacco smoking. All these risk factors have
been shown to be more common among HIV-infected individuals than among uninfected
ones.1,4,5,25,26 Furthermore, mortality in HIV patients without such risk factors was found to
be very similar to that of the non-HIV-infected individuals in a Danish cohort.26 In particular,
the poorer survival observed among HIV-infected people via IDU was recently reported to be
mostly due to HCV co-infection.27 In our study, PWA infected via IDU reported also very
high SMRs.
As expected, extremely high SMRs were documented for the three ADCs, which were
strongly associated with viruses.28 Very high excess risk emerged also for the group of not
otherwise specified uterine cancers where several misclassified cervical cancers are
included.29
Among non-ADCs, very high excess risks were registered for Hodgkin lymphoma
(associated to EBV28) and anal carcinoma (associated to HPV28), two cancers that deserve
particular attention as the elevated corresponding SMRs were due to the combination of their
relative paucity in the general population and to their increased incidence among HIVinfected
people.15,19,22 Of note, 2 out of 5 PWA death certificates reporting anal cancer
mentioned also Kaposi sarcoma, in line with findings of a large prospective cohort of HIVpositive
individuals.21 This cancer was also found to be more frequent among homosexual
PWA19 (3 out of 5 cases, in our study). Liver cancer, which is strongly associated to infection
with hepatitis C and B viruses,28 showed a particularly high SMR, especially among IDU
PWA, similarly to other studies.19 This tumor was reported together with liver cirrhosis
10 code K74.6) in 10 out of 17 death certificates (59%) and with chronic viral hepatitis C
(HCV, ICD-10 code B18.2) in 5 cases (29%). Highly significant excess risks of death were
also seen for lung and head and neck cancers -associated with tobacco smoking-28 in
particular among PWA infected through IDU but also among PWA who died at age 50-74
years (an age period in which lung cancer is very common also among the general
population14). On the other hand, colorectal cancer, leukemia, and skin melanoma -which
also reported significant SMRs- were not generally found to be at increased incidence risk
among HIV/AIDS patients.15,19 The excess death risk observed for these cancers can be
explained by a poorer survival of HIV/AIDS patients after cancer onset.15,23 Some
misclassification of anal cancer into rectal cancer in death certificates cannot be excluded
(SMR=19.0; 95% CI: 7.6-39.1 for rectal cancer, see Table A, Supplemental Digital Content,
http://links.lww.com/QAI/A820).
The spectrum of non-ADCs, for which we found excess mortality, and the magnitude of
SMRs are in line with our previous investigation11 and with other studies conducted in highincome
countries.1,4,6,20 The proportion of deaths associated to non-ADCs was higher in the
present study, referring to the period 2006-2011, than in the previous one conducted in the
period 1999-200611 (10.3% vs. 7.4%). This difference did not seem attributable to the use of
MCoD: among the 17 death certificates of PWA that reported more than one cancer, the
majority were ADCs. The increasing proportion of non-ADCs at death is in agreement with
findings of other investigations.1,3,6 Indeed, this proportion increased from 9% in 1999-2000
to 23% in 2009-2011 among HIV-positive individuals under treatment in a large multi-cohort
collaboration,3 and from 7% to 16.9% between 1996-1997 and 2006-2011 among PWA in
San Francisco.6
Among the main strengths of this study is the use of MCoD data, which allowed direct
comparisons with non-PWA for all the conditions contributing to death without the need to
resort to a manual review of death certificates, as customary in earlier studies;10,11 thus,
improving reproducibility. Comparisons based on the underlying cause may be affected by
poor detail and would prevent to identify specific conditions.6,8 Indeed, in our data 73% (293
cases) of PWA reporting a cancer in death certificate had HIV/AIDS codes as the underlying
cause of death (i.e., ICD-10 codes B20-B24) –a value similar to that observed in other
investigations,8 often with a poor level of detail (e.g., 50% had ICD-10 code B22.7="HIV
disease resulting in multiple diseases", 7% had unspecific cancer codes B21.7-21.8).
Issues of reliability regarding causes of death derived from death certificate statistics are
well known,30 including a possible lack of specificity and/or underreporting due to the limited
knowledge of the certifying physician regarding the medical history of the deceased. This
could have differently affected the compilation of death certificates of people with or without
HIV infection. Nonetheless, in our investigation, the same coding rules were applied to both
study groups, thus limiting information bias.
It is worth remembering that our data included only HIV-infected individuals having
already had an AIDS diagnosis. Thus, study results cannot be referred to HIV-infected people
at an earlier stage of immunodeficiency. In particular, given that AIDS diagnosis can be a
consequence of the diagnosis of an ADC, SMRs for ADCs could be much lower in the case
of HIV-infected people without AIDS (in our data, approximately 84% of PWA reporting
ADCs at death reported also ADCs at diagnosis).
The limited number of person-years at risk, resulting in a low number of observed deaths
for specific cancer types, was also a study limitation. However, given that most of PWA
deaths occurred within the first 6 months after AIDS diagnosis,12 the median follow-up of 2.5
years was sufficiently long for observing most of the events of interest. Nonetheless, SMRs
for very a low number of deaths should be interpreted with caution.
Completeness was the main strength of this investigation. The full coverage of the Italian
population by the two used data sources allowed robust comparisons between PWA and the
general population. Furthermore, the high sensitivity of the record-linkage procedure,15,16
allowed to keep the number of losses to follow-up very limited.
In conclusion, study findings stress the need of monitoring the burden of both virus-related
and non virus-related cancers among PWA in the late HAART era, as they are at still
at a higher risk of death than the HIV-negative population. This applies in particular to PWA
who acquired HIV infection through IDU. Indeed, our results call for taking primary and
secondary preventive actions to reduce both cancer incidence and mortality among people
with HIV or AIDS.
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