A small proportion of people living with HIV continue to develop Kaposi's sarcoma (KS), a cancer linked to immune suppression, according to studies presented at the 22nd International AIDS Conference (AIDS 2018) in Amsterdam.
One analysis found that some people develop new KS or experience KS recurrence even after they start taking antiretroviral therapy (ART) and see a rise in their CD4 count. A second study observed a pocket of higher KS prevalence among African-American men in the US south.
Kaposi's sarcoma, once frequently seen among people with Aids, decreased dramatically with the advent of effective ART and a decline in the number of people living with HIV experiencing CD4 counts falling to very low levels. However, it remains the most common Aids-defining cancer, even as rates of some non-Aids-defining cancers are rising as people with HIV live longer.
Romain Palich of Pitié-Salpêtrière Hospital in Paris presented an analysis of cases of KS in people with sustained viral suppression that were reported to ONCOVIH, a French national multidisciplinary committee that collects data on cancer among people living with HIV.
This observational study included all reported cases of either a first diagnosis of KS or a relapse of KS occurring in people who had been on ART for at least a year and had undetectable plasma viral load (<50 copies/ml).
The committee registered a total of 72 KS cases between May 2014 and December 2017. It was the second most common cancer after lung cancer (96 cases), and was followed by another Aids-defining cancer, non-Hodgkin lymphoma (NHL; 58 cases). These were followed by a variety of non-Aids-defining cancers including anal cancer (32 cases), oral cancer (28 cases), breast cancer (20 cases) and bladder cancer (16 cases). Liver cancer – associated with hepatitis B and C – was uncommon (9 cases) and there were no reported cases of prostate cancer.
Of the people with KS, 21 met the viral suppression criteria. Of the remainder, just over half had a viral load above 50 copies/ml and the rest were missing data. Among the 21 people with new or recurrent KS while virally suppressed, 80% were men. The median age was 54 years; half were born in Africa. They had been diagnosed with HIV a median of 14 years prior and the median duration of viral suppression was 3 years.
Of the KS cases, 40% were first-time diagnoses while 60% were relapses, sometimes many years after the previous occurrence. All patients had KS skin lesions and many had additional manifestations including lesions of the lymph nodes (27%), bronchial tubes (18%), bones (18%), stomach or oesophagus (14%), and mucous membranes of the mouth (5%). Just under half had received treatment for the current KS episode.
The median CD4 count at the time of KS diagnosis was 449 cells/mm3, though it ranged as high as 625 cells/mm3. Nearly half had a CD4 count over 500 cells/mm3 when diagnosed; only 19% had fewer than 200 cells/mm3, the traditional threshold for advanced immune suppression. The median CD4 level was a bit lower for new compared with recurrent cases (375 vs 478 cells/mm3, respectively). The median CD4 nadir, or lowest-ever level was 196 cells/mm3 (ranging from 84 to 329 cells/mm3). The median CD4/CD8 cell ratio was 0.58.
Palich noted that a related study by the European CD4/CD8 Ratio and Cancer Working Group of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) looked at the link between CD4 and CD8 levels and the occurrence of KS and NHL in people with viral suppression. A persistently abnormal CD4/CD8 ratio despite treatment reflects ongoing immune dysfunction.
This analysis included more than 58,000 patients who achieved virological control (here defined as <500 copies/ml) within 9 months after starting ART. The quarter of patients who experienced restoration of a normal CD4/CD8 ratio along with CD4 cell recovery were slightly less likely to develop KS. People with a high CD8 count at baseline had the greatest risk of developing NHL. Those who experienced virological treatment failure were at much higher risk for both KS and NHL.
Returning to the ONCOVIH analysis, 14 people started treatment according to committee recommendations. Seven received anthracyclines (chemotherapy drugs such as doxorubicin), four received taxanes (the chemotherapy class that includes paclitaxel) and three couldn't receive either due to intolerability and tried other therapies. Seventeen patients continued on their current ART regimen while four were advised to modify their regimen due to drug interactions or resistance.
Of the nineteen patients with adequate follow-up, six had partial KS regression or remission, six had stable disease and four experienced disease progression. Plaich acknowledged that these patients might not be representative, as more challenging cases might have been disproportionately referred to the committee.
KS progression despite treatment and the toxicity of conventional chemotherapy leads some people to a "therapeutic dead end," Palich said, suggesting that immunotherapies such as PD-1 checkpoint inhibitors might warrant a pilot study for people with persistent KS that does not respond to standard therapy.
KS in the US
In another study, Elizabeth Chiao of Baylor College of Medicine in Houston, Texas, and colleagues analysed trends in KS incidence among men living with HIV aged 20 to 54 years in the US (women were excluded due to their low number of KS cases). They used data from the US Cancer Statistics registry for the years 2000 to 2014, which covers all 50 states and nearly 100% of the population.
More than 12,500 men were diagnosed with KS during the study period, according to the study abstract. KS incidence declined by about 4% per year overall from 2000 to 2014, but there were notable demographic and regional differences.
Looking at all racial and ethnic groups together, the biggest decrease in new KS cases was seen in the 30 to 44 age group. KS significantly increased among men aged 20 to 29 and remained unchanged among those aged 45 to 54, Chiao reported. African-American and Latino men saw a steeper decline in KS than white men. However, at the end of the study period in 2014, the Latino incidence rate remained well above that of white men, while the rate among black men was more than double that of Latinos.
Adjusting for age, KS incidence dropped steeply in the west and north-east, and less so in the south and mid-west. While KS declined substantially in cities with large early HIV epidemics, including New York, San Francisco, Los Angeles and Miami, it rose over time in Atlanta. In fact, in 2014 the incidence of KS in Atlanta was nearly twice that of New York.
Looking at all these factors together, Chiao said that there was no significant overall change in KS incidence among African-American men in the southern US, and there was actually a significant increase among black men in the youngest age group.
Asked to speculate about the reason for these disparities, she suggested that black men in the south – especially young men – may have less access to HIV testing and other care.
Based on these findings, Chiao recommended that future KS epidemiology, treatment and prevention "should focus on closing the persistent gaps in regional, racial and age disparities" identified in KS incidence.
Background: Kaposi disease (KD) is among the most frequent HIV associated cancers, classically occurring in HIV-replicating individuals. Since 2014, the ONCOVIH national multidisciplinary committee (MDC) registers cancers in HIV infected patients. We report our experience of KD occurring in patients despite sustained virological suppression.
Methods: This observational and national study enrolled all cases of individuals with a first episode or a relapse of KD, on ART for at least 12 months, with a plasma viral load (pVL) < 50cp/ml at the time of KD diagnosis. Results: The French ONCOVIH MDC registered a total of 72 KD cases between 05/2014 and 11/2017. We included for analysis the 22/ 72 (31%) who fulfilled inclusion criteria, whereas 38/72 (53%) had pVL >50 cp/ml at the time of KD diagnostic, and 12 had missing data. They were 18 male and 4 female, born in France for 10 of them and in Africa for 12, with a median age of 51 years (IQR 34-61). HIV infection was diagnosed 12 years earlier (IQR 5-14). CD4 nadir was 200/mm3 (IQR 73-290), and median duration of virological suppression 4 years (IQR 2-5). KD was a relapse in 59% of cases, and a first episode in 41%. KD localisations involved skin (100% of cases), lymph nodes (27%), bronchi (18%), oesophagus/stomach (14%), bone (14%), and/or palate (5%). Median CD4 count was 478/mm3 (IQR 269-630) with a CD4/CD8 ratio of 0.58 (IQR 0.34-0.75). At time of MDC, KD therapy had included anthracyclines in 36% of cases and/or taxanes in 27% of cases. In November 2017, from the follow up of 16/22 patients, all were alive, with a KD in partial remission in 31% of cases, stability in 38% and progression in 31%.
Conclusions: Kaposi disease is observed in aging patients with suppressed viremia either as relapse or new case. HHV-8 as main cause for KD need to be further investigated. Follow up should bring information towards treatment response. Anti PD1 may deserve a pilot investigation in patients failing standard anti-KD chemotherapies.
R Palich, M Veyri, MA Valantin, AG Marcelin, F Boué, A Guihot, C Solas, H Ait-Mohand, V Martinez, I Poizot-Martin, D Costagliola, JP Spano, C Katlama, ONCOVIH Study Group
Background: A persistently abnormal CD4/CD8 ratio despite combination antiretroviral therapy (cART) reflects ongoing immune dysfunction and has been inversely correlated with the risk of non-AIDS defining cancer in people living with HIV (PLHIV). However the predictive value of the CD4/CD8 ratio has never been studied for AIDS-defining cancers such as Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) which remain the most frequent cancers in PLHIV receiving cART. Here, we evaluated the impact of CD4/CD8 ratio restoration (≥1) on KS and NHL risks in PLHIV achieving suppressed viraemia on cART.
Methods: PLHIV from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load≤500 copies/mL) within 9 months following cART initiated between 2000 and 2014. Baseline was the time of the first CD4/CD8 measurement after virological control, with persistent suppressed viraemia. Patients with KS or NHL before baseline were excluded. Cox models were used to identify factors associated with KS and NHL risks.
Results: A total of 58308 patients (76% men, median[IQR] age 38 [32-45] years) were followed-up during 59[30-96] months. At baseline, CD4 count, CD8 count and CD4/CD8 ratio were 412[292-550]/mm3, 937[668-1306]/mm3 and 0.43[0.28-0.64] respectively. Overall, 221 KS and 187 NHL were diagnosed, 9[2-37] and 18[7-42] months after baseline respectively. At 2 years, CD4/CD8 ratio was restored (≥1) in 28% (95%CI:27-28). CD4/CD8 ratio restoration, in addition to CD4 restoration, tended to decrease KS risk (see table). High baseline CD8 count was associated with higher NHL risk. Both KS and NHL risks were strongly increased in case of virological failure.
Conclusions: In this population of patients who had achieved suppressed viraemia, restoration of the CD4/CD8 ratio may confer an additional benefit to CD4 restoration with regard to KS risk. For NHL risk, the main immunological associated factor was baseline CD8 count. Furthermore, avoiding virological failure appeared to be key to minimize KS and NHL risks. A closer clinical monitoring should be proposed in patients with high CD8 count despite virological control and/or low persistent CD4/CD8 ratio.
F Caby, S Grabar, on behalf of the CD4/CD8 Ratio and Cancer Working Group of the COHERE in EuroCoord
Background: Kaposi sarcoma (KS) is the most common neoplasm of people living with HIV today. Although the overall incidence of KS has been reported to be declining in the US, KS has strong racial/ethnic, age, and regional diversity in incidence trends.
Methods: We analyzed KS incidence data from the US Cancer Statistics (USCS) registry for the years 2000-2014. The USCS registry is the official data source for federal government-reported cancer incidence statistics and covers 97% of the US population. Women were excluded because of the low numbers of KS cases in certain geographic regions, and our analyses only included 20 to 54 year-old age-group as prior validation studies indicated that ~94% of KS cases in this age-range are HIV-related. We calculated adjusted incidence rates and assessed annual trends among sociodemographic and geographic subgroups using joinpoint regression analysis.
Results: During the study period, 12,549 men were diagnosed with KS. The overall incidence of KS among men decreased from 1.42/100,000 in 2000 to 0.95/100,000 in 2014, decreasing by 3.60% (95% confidence interval [CI], -4.00% to -3.13%) annually. The overall annual percent change (APC) for men significant decreased (-6.27%, p< 0.05) from 2007-2010 and again (-2.13%, p< 0.05) from 2010-2014. Among African American, non-Hispanic Caucasian, and Hispanic men, the incidences in 2014 were 2.37/100,000, 0.49/100,000, and 1.22/100,000, respectively. Although there was a decrease in the APC among African American men from 2000-2014 (-3.31%, p< 0.05), there were differences in the rate of change among African American men by region. In the Northeast, the APC was noted to have 3 joinpoints, with non-significant decreases in incidence in years 2009-2012 (APC=-0.23%, p< 0.05), followed by a significant decrease in years 2012-2014 (APC=-26.17%, p< 0.05). In the Midwest and West there were significant decreases throughout years 2000-2014 (APC=-3.4%, p< 0.05, and APC=-5.59%, p< 0.05, respectively). However, in the South, there has been no significant change in incidence (APC=-0.86%, p>0.05) of KS among African American men.
Conclusions: Geographic disparities in KS incidence remain for African American men in the U.S. Between the years 2000-2014, unlike other regions, the incidence of KS has remained unchanged in the southern U.S.
E Chiao, T Aaron, Y Dong, R Kathryn, J Kramer, W Donna
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[link url="http://programme.aids2018.org/Abstract/Abstract/12479"]AIDS 2018 abstract 12479[/link]
[link url="http://programme.aids2018.org/Abstract/Abstract/7715"]AIDS 2018 abstract 7715[/link]
[link url="http://programme.aids2018.org/Abstract/Abstract/12150"]AIDS 2018 abstract 12150[/link]