By Carol A. Kemper, MD, FACP

Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases, Santa Clara Valley Medical Center Dr. Kemper reports no financial relationships relevant to this field of study.

The Great Leveler

SOURCE: Zuckerman NS, Mor Z, Bucris E, et al. Sexual intermingling of Arab and Jewish MSM in Israel: Results of a molecular epidemiology study. AIDS 2019;33:339-344.

It has been said that sex is the great leveler. In this epidemiological and molecular study, researchers examined interethnical/religious connections of HIV-1 virus between Arab and Jewish men who have sex with men (MSM) in Israel, suggesting a high degree of shared mutations. In 2016, there were ~7,500 HIV-positive individuals living in Israel, including about 3,349 HIV-positive males. Using a National Civil Registry, the researchers could cross-match the religious affiliation of all of the HIV-positive MSM diagnosed between 2005 and 2016 (n = 1,143). Among these MSM, 93.6% were Jews and 6.4% were Arabs (a higher proportion of Arab HIV-positive patients was observed among non-MSM compared with MSM [19% vs. 6.4%]).

Using a stratified random selection design, researchers selected ~40% of the HIV in each year for subtype analysis and sequencing (including 440 MSM Jews and 62 MSM Arabs). Subtype B was the most common subtype identified among Israeli-born HIV-positive MSM (80.6% of MSM Jews and 82.3% of MSM Arabs). The proportion of the various subtypes (A, B, C, and non-A/B/C) between the two groups was remarkably similar.

The overall prevalence of transmitted drug resistance mutations (TDRM) was 13.1%. The distribution of TDRM was similar between Jews and Arabs (14.1% and 9.7%, respectively; P = NS). The most common TDRM was K103 N/S in 9%, followed by PR-L90 in 3.2%, M184V in 1.2%, and T215S in 1%.

Phylogenetic analysis revealed multiple clusters within subtypes between Arab and Jewish MSM. In HIV subtypes A and C, the most common TDRM (K103) formed two single larger shared clusters, although a subset of patients with one base pair change (K103S) was identified in later years (2013-2014) within subtype A. In contrast, within subtype B, multiple clusters were identified, including five large clusters and 31 smaller clusters of less than four individuals. Arab and Jewish MSM sequences were intermingled within these clusters. Investigators observed two larger clusters with specific mutations, with a common ancestor in one dating back to the 1990s, and the K103N mutation appearing more than 10 years later. Such clustering is highly suggestive of a shared common TDRM with secondary transmission, intermingled between the two groups.

Increased Cancer Risk in HIV (Even With Long-Term Suppression)

SOURCE: Park LS, Tate JP, Sigel K, et al. Association of viral suppression with lower AIDS-defining and non-AIDS-defining cancer incidence in HIV-infected veterans: A prospective cohort study. Ann Intern Med 2018;169:87-96.

After more than 25 years of attempting to control HIV infection and lipid levels (and treat sexually transmitted diseases), I have been faced with a number of non-AIDS-related solid tumors in my HIV-positive patients, especially in my older patients (including several lung cancers, pancreatic cancer, two patients with melanoma, and one with throat cancer). So, I found this article from the National Cancer Institute (NCI) and the Department of Veterans Affairs of particular interest.

These authors performed a large, prospective cohort study comparing rates of AIDS-defining cancers and non-AIDS-defining cancers in 42,441 HIV-positive veterans vs. 104,712 demographically matched non-HIV-positive veterans from 1999-2015. The investigators standardized the incidence rates of AIDS-defining and non-AIDS-defining malignancies by viral suppression status. The status was defined as unsuppressed; early suppression, meaning the initial two years of observation with HIV RNA levels < 500 copies/mL; and long-term suppression, allowing for only one “blip” greater than 1,000 copies/mL. Those patients who became unsuppressed after a period of early or long-term suppression and then were suppressed again were classified as early suppression, at least during the initial two years of the observation period (i.e., the clock was reset).

More than half (62%) of the HIV-positive veterans achieved long-term suppression during follow-up. Compared with HIV-negative veterans, HIV-positive persons had a higher prevalence of chronic hepatitis C virus infection (22% vs. 10%) and a lower prevalence of diabetes (21% vs. 34%).

For each cancer type, researchers calculated standardized weights based on person-time distribution by age (five-year groups) for various time intervals. They included in the analysis only those cancer types with at least 30 cases.

Compared with HIV-negative veterans, cancer incidence was highest for the unsuppressed group (relative risk [RR], 2.35; 95% confidence interval [CI], 2.19-2.51), lower among those with early suppression (RR, 1.99), and lowest among those with long-term suppression (1.52). This observation was strongest for AIDS-defining malignancies, but non-AIDS-defining malignancies followed a similar trend. Compared with HIV-negative veterans, the relative risk of non-AIDS-defining cancers was highest for the unsuppressed group (RR, 3.82; CI, 3.24-4.49), lower for those with early suppression (RR, 3.42, CI, 2.95-3.97), and lowest for those with long-term suppression (RR, 3.17; CI, 2.78-3.62).

Note that long-term suppression was associated with a 23% reduction in excess risk, but even those with long-term suppression remained at significantly higher risk for non-AIDS-related cancers. These predominately included non-HPV-cancers of the oropharynx and larynx, pancreatic and lung cancers, and melanoma. Other lymphoproliferative and hematologic malignancies, such as multiple myeloma and leukemias, also were increased, especially in the unsuppressed and early suppression groups. Only the relative risk of prostate cancer appeared unaffected by HIV status. And that is exactly what I am seeing.