Association between KSHV-Specific Humoral and T Cell Responses with Recurrence of HIV-Associated Kaposi Sarcoma.

Kaposi sarcoma (KS) is an AIDS-defining angio-proliferative malignancy, with the Kaposi sarcoma-associated herpes virus (KSHV) as its etiologic agent. Upon treatment with chemotherapy, a proportion of HIV-associated KS patients experience disease recurrence within a few months of completing treatment. We aimed at determining whether KSHV-specific adaptive immune responses were associated with KS recurrence upon complete remission. We conducted a prospective cohort study. The primary outcome was the recurrence of HIV-associated KS. An immunofluorescence assay was used to determine anti-KSHV antibodies, an enzyme-linked immunospot was conducted for T cell responses, PCR was carried out to determine KSHV status, and flow cytometry was used for CD4 counting and immunophenotyping. KSHV detection in PBMCs was high and not associated with KS recurrence-free survival (p = 0.29). Anti-KSHV antibody titers were high and not associated with recurrence-free survival (p = 0.63). KSHV-specific T cell responses dropped from baseline levels among individuals with recurrence, but the drop was not statistically significant. Individuals experiencing KS recurrence had a significantly higher proportion of T cell subsets expressing PD1, while those with sustained remission had a significant increase in CD4 T cell counts from baseline levels during the follow-up period (p = 0.02). Anti-KSHV antibodies are not a good correlate of protection from KS recurrence. T cells in individuals experiencing KS recurrence hadhigh PD1 expression, while an increase in CD4 counts was associated with sustained KS remission.

Comparison of HIV prevalence, incidence, and viral load suppression in Zambia population-based HIV impact assessments from 2016 and 2021.

BACKGROUND: The Zambian government has implemented a public health response to control the HIV epidemic in the country. Zambia conducted a population-based HIV impact assessment (ZAMPHIA) survey in 2021 to assess the status of the HIV epidemic to guide its public health programs. METHODS: ZAMPHIA 2021 was a cross-sectional two-stage cluster sample household survey among persons aged ≥15 years conducted in Zambia across all 10 provinces. Consenting participants were administered a standardized questionnaire and whole blood was tested for HIV according to national guidelines. HIV-1 viral load (VL), recent HIV infection, and antiretroviral medications were tested for in HIV-seropositive samples. Viral load suppression (VLS) was defined as <1000 copies/ml. ZAMPHIA 2021 results were compared to ZAMPHIA 2016 for persons aged 15-59 years (i.e., the overlapping age ranges). All estimates were weighted to account for nonresponse and survey design. RESULTS: During ZAMPHIA 2021, of 25 483 eligible persons aged ≥15 years, 18 804 (73.8%) were interviewed and tested for HIV. HIV prevalence was 11.0% and VLS prevalence was 86.2% overall, but was <80% among people living with HIV aged 15-24 years and in certain provinces. Among persons aged 15-59 years, from 2016 to 2021, HIV incidence declined from 0.6% to 0.3% ( P -value: 0.07) and VLS prevalence increased from 59.2% to 85.7% ( P -value: <0.01). DISCUSSION: Zambia has made substantial progress toward controlling the HIV epidemic from 2016 to 2021. Continued implementation of a test-and-treat strategy, with attention to groups with lower VLS in the ZAMPHIA 2021, could support reductions in HIV incidence and improve overall VLS in Zambia.

Progressive multifocal leukoencephalopathy in Zambia is caused by JC virus with prototype regulatory region.

There are only few documented cases of progressive multifocal leukoencephalopathy (PML) in Africa. Whether this is caused by a lack of JC virus (JCV) spread or alteration in the JCV genome is unknown. We characterized the clinical presentation, laboratory findings, and JCV regulatory region (RR) pattern of the first documented PML cases in Zambia as well as JCV seroprevalence among HIV+ and HIV- Zambians. We identified PML patients with positive JCV DNA PCR in their cerebrospinal fluid (CSF) among subjects enrolled in an ongoing tuberculous meningitis study from 2014 to 2016 in Lusaka. JCV regulatory region was further characterized by duplex PCR in patients' urine and CSF. Of 440 HIV+ patients, 14 (3%) had detectable JCV DNA in their CSF (age 18-50; CD4+ T cells counts 15-155 × 106/µl) vs 0/60 HIV- patients. The main clinical manifestations included altered mental status and impaired consciousness consistent with advanced PML. While prototype JCV was identified by duplex PCR assay in the CSF samples of all 14 PML patients, only archetype JCV was detected in their urine. All PML Zambian patients tested were seropositive for JCV compared to 46% in a control group of HIV+ and HIV- Zambian patients without PML. PML occurs among HIV-infected individuals in Zambia and is caused by CNS infection with prototype JCV, while archetype JCV strains are present in their urine. JCV seroprevalence is comparable in Zambia and the USA, and PML should be included in the differential diagnosis of immunosuppressed individuals presenting with neurological dysfunction in Zambia.