A prospective cohort study identifies two types of HIV+ Kaposi Sarcoma lesions: proliferative and inflammatory.

Kaposi sarcoma (KS) is the most common cancer in people living with HIV (PLWH) in many countries where KS-associated herpesvirus is endemic. Treatment has changed little in 20 years, but the disease presentation has. This prospective cohort study enrolled 122 human immunodeficiency virus (HIV) positive KS patients between 2017 and 2019 in Malawi. Participants were treated with bleomycin, vincristine and combination antiretroviral therapy, the local standard of care. One-year overall survival was 61%, and progression-free survival was 58%. The 48-week complete response rate was 35%. RNAseq (n = 78) differentiated two types of KS lesions, those with marked endothelial characteristics and those enriched in inflammatory transcripts. This suggests that different KS lesions are in different disease states consistent with the known heterogeneous clinical response to treatment. In contrast to earlier cohorts, the plasma HIV viral load of KS patients in our study was highly variable. A total of 25% of participants had no detectable HIV; all had detectable KSHV viral load. Our study affirms that many KS cases today develop in PLWH with well-controlled HIV infection and that different KS lesions have differing molecular compositions. Further studies are needed to develop predictive biomarkers for this disease.

Comparison of baseline lymphoma and HIV characteristics in Malawi before and after implementation of universal antiretroviral therapy.

Access to antiretroviral therapy (ART) led to epidemiological changes in human immunodeficiency virus (HIV) associated lymphoma in high-income countries such as reductions in diffuse large B-cell lymphoma (DLBCL) and stable or increased Hodgkin lymphoma (HL) and Burkitt lymphoma (BL). In 2016, Malawi implemented a universal ART (UART) policy, expanding ART eligibility to all persons living with HIV (PLWH). We compare the distribution of lymphoma subtypes and baseline HIV and prognostic characteristics for lymphoma patients in Malawi before and after implementation of UART. We enrolled patients with pathologically confirmed incident lymphoproliferative disorders into a observational clinical cohort. At diagnosis, a comprehensive clinicopathological evaluation was performed. Of 412 participants, 156 (38%) were pre-UART (2013-June 2016) and 256 (62%) post-UART (July 2016-2020). HIV prevalence was 50% in both groups. The most common pre-UART diagnoses were DLBCL [75 (48%)], low-grade non-Hodgkin lymphoma (NHL) [19 (12%)], HL [17 (11%)] and, BL [13 (8%)]. For post-UART they were DLBCL [111 (43%)], NHL [28 (11%)], BL [27 11%)] and, HL [20 (8%)]. Among PLWH, 44 (57%) pre-UART initiated ART prior to lymphoma diagnosis compared to 99 (78%) post-UART (p = 0.02). HIV-ribonucleic acid was suppressed <1000 copies/mL in 56% (33/59) pre-UART and 71% (73/103) post-UART (p = 0.05). CD4 T-cell counts were similar for both groups. We observed similar findings in the subset of participants with DLBCL. Overall, there were no significant changes in incident lymphoma subtypes (p = 0.61) after implementation of UART, but HIV was better controlled. Emerging trends bear monitoring and may have implications for prognosis and health system priority setting. Trial registration: ClinicalTrials.gov identifier: NCT02835911.

Spatial distribution of incident pediatric Burkitt lymphoma in central and northern Malawi and association with malaria prevalence.

BACKGROUND: Burkitt lymphoma (BL) accounts for 90% of pediatric lymphomas in sub-Saharan Africa. Plasmodium falciparum malaria is considered an etiological factor of BL. We describe the geographic distribution of pediatric BL in Malawi and association with P. falciparum malaria prevalence rate (PfPR). METHODS: We enrolled 220 pathologically confirmed incident pediatric BL cases (2013-2018) into an observational clinical cohort at Kamuzu Central Hospital (KCH) in Lilongwe district. KCH is the main tertiary cancer referral center serving the central and northern regions of Malawi. Using an ecological study design, we calculated district-level annual BL incidence rate using census population estimates. District-level PfPR was extracted from the National Malaria Control Program 2010 report. BL incidence and PfPR maps were constructed in QGIS. Moran's I  test was used to identify BL spatial clusters. Pearson's correlation and multiple linear regression analyses were used to statistically examine the relationship between PfPR and BL. RESULTS: BL incidence was higher in central region districts (8.2 cases per million) than northern districts (2.9 cases per million) and was elevated in lakeshore districts. Districts with elevated PfPR tended to have elevated BL incidence. A low-risk BL cluster was detected in the north. Statistically, BL incidence was positively correlated with PfPR (r = .77, p < .01). A 1% increase in PfPR predicted an increase in BL incidence of 0.2 cases per million (p = .03), when controlling for travel time from referral district hospital to KCH. CONCLUSION: Our study supports evidence for an association between P. falciparum and BL and highlights a need to improve geographic accessibility to tertiary cancer services in Malawi's northern region.