Association of Viral Suppression With Lower AIDS-Defining and Non-AIDS-Defining Cancer Incidence in HIV-Infected Veterans: A Prospective Cohort Study

Abstract

Background: Viral suppression is a primary marker of HIV treatment success. Persons with HIV are at increased risk for AIDS-defining cancer (ADC) and several types of non-AIDS-defining cancer (NADC), some of which are caused by oncogenic viruses.

Objective: To determine whether viral suppression is associated with decreased cancer risk.

Design: Prospective cohort.

Setting: Department of Veterans Affairs.

Participants: HIV-positive veterans (n = 42 441) and demographically matched uninfected veterans (n = 104 712) from 1999 to 2015.

Measurements: Standardized cancer incidence rates and Poisson regression rate ratios (RRs; HIV-positive vs. uninfected persons) by viral suppression status (unsuppressed: person-time with HIV RNA levels ≥500 copies/mL; early suppression: initial 2 years with HIV RNA levels <500 copies/mL; long-term suppression: person-time after early suppression with HIV RNA levels <500 copies/mL).

Results: Cancer incidence for HIV-positive versus uninfected persons was highest for unsuppressed persons (RR, 2.35 [95% CI, 2.19 to 2.51]), lower among persons with early suppression (RR, 1.99 [CI, 1.87 to 2.12]), and lowest among persons with long-term suppression (RR, 1.52 [CI, 1.44 to 1.61]). This trend was strongest for ADC (unsuppressed: RR, 22.73 [CI, 19.01 to 27.19]; early suppression: RR, 9.48 [CI, 7.78 to 11.55]; long-term suppression: RR, 2.22 [CI, 1.69 to 2.93]), much weaker for NADC caused by viruses (unsuppressed: RR, 3.82 [CI, 3.24 to 4.49]; early suppression: RR, 3.42 [CI, 2.95 to 3.97]; long-term suppression: RR, 3.17 [CI, 2.78 to 3.62]), and absent for NADC not caused by viruses.

Limitation: Lower viral suppression thresholds, duration of long-term suppression, and effects of CD4+ and CD8+ T-cell counts were not thoroughly evaluated.

Conclusion: Antiretroviral therapy resulting in long-term viral suppression may contribute to cancer prevention, to a greater degree for ADC than for NADC. Patients with long-term viral suppression still had excess cancer risk.

Primary funding source: National Cancer Institute and National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Figure 1.. Numbers of cancer cases, IRs (per 100,000 personRRs* with 95% CI by HIV viral suppression status, and P cancer groups†

ADC = AIDS-defining cancer; IR = age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rate; non-virus-NADC = non-virus-related non-AIDS-defining cancer; RR = adjusted incidence rate ratio; virus-NADC = virus-related non-AIDS-defining cancer; 95% CI = 95% confidence interval. *Adjusted for time-updated age, sex, race/ethnicity, time-updated calendar period, smoking, alcohol abuse/dependence, hepatitis C virus infection, and diabetes. †For cancer group analyses, the endpoint for a given subject was the first diagnosis of a cancer type classified in the group. For example, if a person had both a non-Hodgkin lymphoma and Kaposi sarcoma diagnosis, only the first of the two diagnoses would contribute to the ADC analysis.

Figure 2.. Numbers of cancer cases, IRs (per 100,000 person-RRs* with 95% CI by HIV viral suppression status, and P ADC†

ADC = AIDS-defining cancer; IR = age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rate; RR = adjusted incidence rate ratio; 95% CI = 95% confidence interval. *Adjusted for time-updated age, sex, race/ethnicity, time-updated calendar period, smoking, alcohol abuse/dependence, hepatitis C virus infection, and diabetes. †For ADC (cancer group), the endpoint for a given subject was the first diagnosis of a cancer type classified as ADC. For example, if a person had both a non-Hodgkin lymphoma and Kaposi sarcoma diagnosis, only the first of the two diagnoses would contribute to the ADC analysis, but both diagnoses would contribute to each specific cancer type analysis. The following cancer type (and number of HIV+ cancer cases) with less than 30 HIV+ cancer cases were not included in the figure, but were included in the ADC analysis: invasive cervical (1).

Figure 3.. Numbers of cancer cases, IRs (per 100,000 personRRs* with 95% CI by HIV viral suppression status, and P virus-NADC†

HCC = hepatocellular carcinoma; HPV = human papillomavirus; IR = age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rate; RR = adjusted incidence rate ratio; SCC = squamous cell carcinoma; virus-NADC = virus-related non-AIDS-defining cancer; 95% CI = 95% confidence interval. *Adjusted for time-updated age, sex, race/ethnicity, time-updated calendar period, smoking, alcohol abuse/dependence, hepatitis C virus infection, and diabetes. †For virus-NADC (cancer group), the endpoint for a given subject was the first diagnosis of a cancer type classified as virus-NADC. For example, if a person had both Hodgkin lymphoma and anal SCC, only the first of the two diagnoses would contribute to the virus-NADC analysis, but both diagnoses would contribute to each specific cancer type analysis. The following cancer types (and numbers of HIV+ cancer cases) with less than 30 HIV+ cancer cases were not included in the figure, but were included in the virus-NADC analysis: penis SCC (17). The following cancer types had no HIV+ cases: vagina SCC; vulva SCC.

Figure 4.. Numbers of cancer cases, IRs (per 100,000 person-years), multivariate Poisson regression values for HIV+ IR viral suppression trend, for RRs* with 95% CI by HIV viral suppression status, and P non-virus-NADC†

HPV = human papillomavirus; IR = age-, sex-, race/ethnicity-, and calendar-period-standardized incidence rate; non-virus-NADC = non-virus-related non-AIDS-defining cancer; RR = adjusted incidence rate ratio; SCC = squamous cell carcinoma; 95% CI = 95% confidence interval. *Adjusted for time-updated age, sex, race/ethnicity, time-updated calendar period, smoking, alcohol abuse/dependence, hepatitis C virus infection, and diabetes. † For non-virus-NADC (cancer group), the endpoint for a given subject was the first diagnosis of a cancer type classified as non-virus-NADC. For example, if a person had both lung cancer and prostate cancer, only the first of the two diagnoses would contribute to the virus-NADC analysis, but both diagnoses would contribute to each specific cancer type analysis. The following cancer types (and numbers of HIV+ cancer cases) with less than 30 HIV+ cancer cases were not included in the figure, but were included in the non-virus-NADC analysis: oral cavity and pharynx non-SCC (9); small Intestine (4); anal non-SCC (5); liver non-hepatocellular carcinoma (12); biliary tract (16); retroperitoneum and peritoneum, nonmesothelioma (1); other digestive organs (3); nose, nasal cavity, and middle ear (12); pleura (2); trachea, mediastinum, and other respiratory organ (1); bone and joint (2); soft issue including heart (21); nonepithelial skin (9); female breast (10); male breast (5); testis (10); other male genital organs (4); other urinary organ (6); eye and orbit (3); brain and nervous system (9); thyroid (25); other endocrine including thymus (1); and mesothelioma (4). The following cancer types (and numbers of HIV+ cancer cases) did not have any HIV+ viral suppression categories with significantly elevated cancer risk and were not included in the figure, but were included in the non-virus-NADC analysis: esophagus (51); stomach (32); colorectal (155); urinary bladder (62); kidney and renal pelvis (115). The following cancer types had no HIV+ cases: corpus or uterus; ovary; vagina non-SCC; vulva non-SCC; other female genital organs; and penis non-SCC. ‡We used sex-specific weights to calculate prostate cancer IRs.