Objective

AIDS-related primary central nervous system lymphoma (AR-PCNSL) has a poor prognosis. Improved understanding of specific patient, infectious, diagnostic, and treatment-related factors that affect overall survival (OS) is required to improve outcomes.

Design

Population-based registry linkage study.

Methods

Adult cases from the San Francisco AIDS registry (1990-2000) were matched with the California Cancer Registry (1985-2002) to ascertain AR-PCNSL data. Survival time was assessed through 31 December 2007. Risk factors and temporal trends for death were measured using two-sided Kaplan-Meier and Cox analyses.

Results

Two hundred and seven AR-PCNSL patients were identified: 68% were white, 20% Hispanic, 10% African-American, and 2% Asian. Nineteen percent of patients had central nervous system (CNS) opportunistic infections diagnosed prior to AR-PCNSL. Fifty-seven percent of patients received radiation and/or chemotherapy and 12% used HAART prior to or within 30 days of AR-PCNSL diagnosis. One hundred and ninety-nine patients died (34 deaths/100 person-years). In adjusted analysis, prior CNS opportunistic infection diagnosis increased risk of death (hazard ratio 1.9, P = 0.0006) whereas radiation and/or chemotherapy decreased risk (hazard ratio 0.6, P < 0.0001). AR-PCNSL diagnosis 1999-2002 had a lower mortality risk (hazard ratio = 0.4, P = 0.02) compared to 1990-1995. African-Americans had an increased risk of death compared to whites or Asians (hazard ratio = 2.0, P = 0.007).

Conclusion

OS among AR-PCNSL patients improved over time but remains poor, especially among African-Americans. Prospective evaluation of curative therapy in AR-PCNSL is urgently needed. Accurate diagnosis of CNS mass lesions in patients with AIDS is required and for those with AR-PCNSL, antiretroviral therapy with concomitant AR-PCNSL therapy, and antimicrobial supportive care may improve OS.

The purpose of the present trial was to determine the feasibility of the daily topical application of the piperidine nitroxide, MTS‑01, combined with chemoradiotherapy in the treatment of patients with anal carcinoma. The secondary study endpoints were the description of the effects of this agent on skin toxicity and rectal‑associated lymphoid tissue. The participants received radiotherapy concurrent with mitomycin‑C and 5‑fluorouracil for carcinoma of the anal canal. MTS‑01 was applied to the bilateral inguinal area and the gluteal cleft. Dermatologic and non‑dermatologic toxicity was graded throughout the treatment period. Circulating lymphocytes were serially collected for phenotyping. Rectal mucosal snag biopsies were collected at baseline and at 1 year of follow‑up. A total of 5 patients received topical MTS‑01. Adverse events attributed to MTS‑01 included asymptomatic grade 1 hypoglycemia and grade 1‑2 diarrhea. Dermatitis within untreated, radiated skin was not more severe than dermatitis in MTS‑01‑treated, unirradiated skin. Circulating CD4⁺ lymphocyte suppression was noted at >1 year following treatment in human immunodeficiency virus‑negative participants. CD4⁺ lymphocytes remained suppressed in the irradiated rectal mucosa at 1 year, whereas the CD8⁺ lymphocyte numbers recovered or increased. On the whole, the present study demonstrates that the MTS‑01 topical application was tolerable with minimal toxicity. Chemoradiation for anal cancer led to prolonged CD4⁺ lymphocytopenia in the circulation and gut mucosa.

In people living with HIV (PLWH) on antiretroviral therapy (ART), virus persists in a latent form where there is minimal transcription or protein expression. Latently infected cells are a major barrier to curing HIV. Increasing HIV transcription and viral production in latently infected cells could facilitate immune recognition and reduce the pool of infected cells that persist on ART. Given that programmed cell death protein 1 (PD-1) expressing CD4⁺ T cells are preferentially infected with HIV in PLWH on ART, we aimed to determine whether administration of antibodies targeting PD-1 would reverse HIV latency in vivo. We therefore evaluated the impact of intravenous administration of pembrolizumab every 3 weeks on HIV latency in 32 PLWH and cancer on ART. After the first infusion of anti-PD-1, we observed a median 1.32-fold increase in unspliced HIV RNA and 1.61-fold increase in unspliced RNA:DNA ratio in sorted blood CD4⁺ T cells compared to baseline. We also observed a 1.65-fold increase in plasma HIV RNA. The frequency of CD4⁺ T cells with inducible virus evaluated using the tat/rev limiting dilution assay was higher after 6 cycles compared to baseline. Phylogenetic analyses of HIV env sequences in a participant who developed low concentrations of HIV viremia after 6 cycles of pembrolizumab did not demonstrate clonal expansion of HIV-infected cells. These data are consistent with anti-PD-1 being able to reverse HIV latency in vivo and support the rationale for combining anti-PD-1 with other interventions to reduce the HIV reservoir.