While 16% of HIV-positive people with Hodgkin lymphoma received no therapy, according to a 2004-2012 U.S. analysis, only 9% of HIV-negative Hodgkin patients went untreated. Lower chemotherapy rates and undefined lymphoma histology in people with versus without HIV could largely explain worse survival statistics in Hodgkin patients with HIV, according to the study.
Hodgkin lymphoma incidence runs five to 20 times higher in people with HIV infection than in HIV-negative populations, and incidence has increased with wide adoption of combination antiretroviral therapy (ART). Four observational studies cited by the authors of this analysis suggest similar Hodgkin survival with or without HIV. In contrast, U.S. population-based studies found poor overall survival with Hodgkin lymphoma in HIV populations. But these population-based analyses lacked information on Hodgkin therapy and ART, and low treatment rates clearly could affect survival.
Data for this analysis came from the National Cancer Data Base (NCDB), which includes more than 70% of all incident cancers in the United States. Although overall survival is the only NCDB endpoint, the system also collects information on demographics, HIV status, cancer histology, stage, first course of therapy and other variables of interest. The researchers extracted data on all 43,935 cases of classical Hodgkin lymphoma recorded between 2004 and 2012, which included overall survival for patients diagnosed up to 2011.
Of the 43,935 people with Hodgkin lymphoma, 2090 (5%) had HIV infection, and the proportion with HIV did not change through the study period. Median age was higher in Hodgkin patients with HIV (43 versus 40 years); the HIV group included a twice-higher proportion between 40 and 59 years old (53.4% versus 26.6%) and a lower proportion of older patients. The HIV Hodgkin group had a much higher proportion of men than the non-HIV group (80.4% versus 52.7%).
Two-thirds of the HIV group (65.6%) had stage III/IV Hodgkin lymphoma, compared with 39.3% of the HIV-negative group. Nodular sclerosis proved the most common histologic subtype in people with and without HIV, but mixed cellularity cases were twice as common in the HIV group.
Among Hodgkin patients with HIV, 81% received chemotherapy, and 12% of those also received radiation, but 16% received no treatment. In contrast, 87% of the HIV-negative group received chemotherapy, 31% of them with radiation, and only 9% received no treatment (P < .00001 for all comparisons). A multivariable logistic regression model linked several factors to not receiving chemotherapy: older age, male gender, nonwhite race, no health insurance, living in an area with the lowest median income, early-stage disease and undetermined histology.
Through a median follow-up of 51 months, the unadjusted five-year overall survival rate with Hodgkin lymphoma was significantly lower in the HIV group (66%, 95% confidence interval [CI] 64% to 68%) than in the HIV-negative group (80%, 95% CI 79% to 80%). Among people who received chemotherapy, unadjusted five-year overall survival was also significantly lower in the HIV group (73%, 95% CI 71% to 75%) than in the HIV-negative group (83%, 95% CI 83% to 84%).
But in a multivariable model limited to patients who received chemotherapy, five-year overall survival did not differ significantly between the HIV group and the HIV-negative group for the four classical histologic subtypes (nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted). Five-year overall survival was significantly lower with HIV than without HIV for patients with undetermined histology (63.5% versus 77.0%, odds ratio 1.56, 95% CI 1.31 to 1.85, P < .0001). This survival difference in patients with undetermined histology drove overall lower survival for all histologies in the HIV group (73.0% versus 83.3%, odds ratio 1.29, 95% CI 1.15 to 1.44, P = .0001). Among HIV-positive people who received chemotherapy, multivariable analysis determined that survival was significantly lower with older age, undetermined histology, advanced stage lymphoma and unfavorable health insurance status.
The researchers believe their results "demonstrate that previous unfavorable survival statistics" in HIV patients with Hodgkin lymphoma "are related to two factors: a higher rate of nontreatment and a poor prognosis in the subgroup with undetermined histologic subtype." Survival was similar with and without HIV for people with classical histologic subtypes who received chemotherapy. These findings, the authors add, underscore "the need for an aggressive approach to obtain an adequate diagnostic sample and to deliver curative therapy, but also for adequate supportive care to assure its safety." They stress that most HIV Hodgkin patients today have the favorable nodular sclerosis morphology "and should not miss the opportunity of upfront cure."