Browsing by Author "Maurer , Toby"

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    An expanded population of CD8dim T cells with features of mitochondrial dysfunction and senescence is associated with persistent HIV-associated Kaposi’s sarcoma under ART
    (Frontiers, 2022-09-29) Clutton, Genevieve T.; Weideman, Ann Marie K.; Goonetilleke, Nilu P.; Maurer , Toby; Dermatology, School of Medicine
    HIV-associated Kaposi’s sarcoma (KS), which is caused by Kaposi’s sarcoma-associated herpesvirus, usually arises in the context of uncontrolled HIV replication and immunosuppression. However, disease occasionally occurs in individuals with durable HIV viral suppression and CD4 T cell recovery under antiretroviral therapy (ART). The underlying mechanisms associated with this phenomenon are unclear. Suppression of viral infections can be mediated by CD8 T cells, which detect infected cells via their T cell receptor and the CD8 coreceptor. However, CD8 T cells exhibit signs of functional exhaustion in untreated HIV infection that may not be fully reversed under ART. To investigate whether KS under ART was associated with phenotypic and functional perturbations of CD8 T cells, we performed a cross-sectional study comparing HIV-infected individuals with persistent KS under effective ART (HIV+ KS+) to HIV-infected individuals receiving effective ART with no documented history of KS (HIV+ KSneg). A subset of T cells with low cell surface expression of CD8 (“CD8dim T cells”) was expanded in HIV+ KS+ compared with HIV+ KSneg participants. Relative to CD8bright T cells, CD8dim T cells exhibited signs of senescence (CD57) and mitochondrial alterations (PGC-1α, MitoTracker) ex vivo. Mitochondrial activity (MitoTracker) was also reduced in proliferating CD8dim T cells. These findings indicate that an expanded CD8dim T cell population displaying features of senescence and mitochondrial dysfunction is associated with KS disease under ART. CD8 coreceptor down-modulation may be symptomatic of ongoing disease.
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    Barriers and facilitators to chemotherapy initiation and adherence for patients with HIV-associated Kaposi's sarcoma in Kenya: a qualitative study
    (Springer, 2022-07-06) McMahon, Devon E.; Singh , Rhea; Chemtai, Linda; Semeere, Aggrey; Byakwaga, Helen; Grant , Merridy; Laker-Oketta , Miriam; Lagat, Celestine; Collier , Sigrid; Maurer , Toby; Martin , Jeffrey; Bassett , Ingrid V.; Butler , Lisa; Kiprono , Samson; Busakhala , Naftali; Freeman, Esther E.; Dermatology, School of Medicine
    Background Kaposi sarcoma is one of the most prevalent HIV-associated malignancies in sub-Saharan Africa and is often diagnosed at advanced stage of disease. Only 50% of KS patients who qualify for chemotherapy receive it and adherence is sub-optimal. Methods 57 patients > 18 years with newly diagnosed KS within the AMPATH clinic network in Western Kenya were purposively selected to participate in semi-structured interviews stratified by whether they had completed, partially completed, or not completed chemotherapy for advanced stage KS. We based the interview guide and coding framework on the situated Information, Motivation, Behavioral Skills (sIMB) framework, in which the core patient centered IMB constructs are situated into the socioecological context of receiving care. Results Of the 57 participants, the median age was 37 (IQR 32–41) and the majority were male (68%). Notable barriers to chemotherapy initiation and adherence included lack of financial means, difficulty with convenience of appointments such as distance to facility, appointment times, long lines, limited appointments, intrapersonal barriers such as fear or hopelessness, and lack of proper or sufficient information about chemotherapy. Factors that facilitated chemotherapy initiation and adherence included health literacy, motivation to treat symptoms, improvement on chemotherapy, prioritization of self-care, resilience while experiencing side effects, ability to carry out behavioral skills, obtaining national health insurance, and free chemotherapy. Conclusion Our findings about the barriers and facilitators to chemotherapy initiation and adherence for KS in Western Kenya support further work that promotes public health campaigns with reliable cancer and chemotherapy information, improves education about the chemotherapy process and side effects, increases oncology service ability, supports enrollment in national health insurance, and increases incorporation of chronic disease care into existing HIV treatment networks.