2 research outputs found
HIV specific CD4+ and CD8+ T cell functionality is reduced in HIV infected individuals co-infected with latent Mycobacterium tuberculosis infection (LTBI) and active Tuberculosis (TB) disease.
<p><b>(A)</b> Representative flow cytometry plots showing cytokine responses for HIV (gag), control (no antigen) for HIV mono-infected subjects, and subjects co-infected with latent MTB infection (LTBI) and active tuberculosis (TB) <b>(B)</b> HIV-specific CD4+ release of IFNγ (p<0.001), TNFα (p<0.01) and IL-2 (p<0.01) were significantly different between all groups (Kruskal-Wallis). <b>(C)</b> HIV-specific CD8+ release of IFNγ (p<0.01) and TNFα (p<0.001) was significantly lower from HIV mono-infected subjects, to those co-infected with active TB. We additionally assessed the polyfunctionality profile of HIV specific CD4+ and CD8+ T cells in all patient groups. The polyfunctionality profiles between groups differed significantly for both CD4+ (p = 0.04) and CD8+ (p<0.001).<b>(D)</b> HIV-specific CD4+ T cells from HIV mono-infected subjects displayed a polyfunctional CD4+ T cell profile with a maximum of four functions being present (IFN<sup>+</sup>IL-2<sup>+</sup>IL-17<sup>+</sup>TNFα (2%)).<b>(E)</b> HIV-specific four function CD4+ T cells were not present in subjects co-infected with LTBI <b>(F)</b> Further decreases in HIV-specific CD4+ T cell polyfunctionality were observed in HIV positive subjects co-infected with TB, being replaced by a largely mono-functional profile with a decreased amount of triple cytokine cells (5% as compared to 13% in HIV/LTBI and 15% in HIV mono-infection). Additionally, single positive TNF-α cells dominated the profile (48%). <b>(G)</b> HIV-specific CD8+ T cells in HIV mono-infected subjects displayed a polyfunctional profile with a maximum of 2 functions being present (IFN<sup>+</sup> TNFα (2%). <b>(H)</b> A maximum of 2 functions (IFN<sup>+</sup>TNFα<sup>+</sup> (28%)) were present in HIV-specific CD8+ cells from subjects co-infected with LTBI. <b>(I)</b> 87% mono-functional cells were present in the HIV-specific CD8+T cell profile from subjects co-infected with TB, suggesting a complete loss of polyfunctionality.</p
The REVAMP trial to evaluate HIV resistance testing in sub-Saharan Africa: a case study in clinical trial design in resource limited settings to optimize effectiveness and cost effectiveness estimates
<p><b>Background:</b> In sub-Saharan Africa, rates of sustained HIV virologic suppression remain below international goals. HIV resistance testing, while common in resource-rich settings, has not gained traction due to concerns about cost and sustainability.</p> <p><b>Objective:</b> We designed a randomized clinical trial to determine the feasibility, effectiveness, and cost-effectiveness of routine HIV resistance testing in sub-Saharan Africa.</p> <p><b>Approach:</b> We describe challenges common to intervention studies in resource-limited settings, and strategies used to address them, including: (1) optimizing generalizability and cost-effectiveness estimates to promote transition from study results to policy; (2) minimizing bias due to patient attrition; and (3) addressing ethical issues related to enrollment of pregnant women.</p> <p><b>Methods:</b> The study randomizes people in Uganda and South Africa with virologic failure on first-line therapy to standard of care virologic monitoring or immediate resistance testing. To strengthen external validity, study procedures are conducted within publicly supported laboratory and clinical facilities using local staff. To optimize cost estimates, we collect primary data on quality of life and medical resource utilization. To minimize losses from observation, we collect locally relevant contact information, including Whatsapp account details, for field-based tracking of missing participants. Finally, pregnant women are followed with an adapted protocol which includes an increased visit frequency to minimize risk to them and their fetuses.</p> <p><b>Conclusions:</b> REVAMP is a pragammatic randomized clinical trial designed to test the effectiveness and cost-effectiveness of HIV resistance testing versus standard of care in sub-Saharan Africa. We anticipate the results will directly inform HIV policy in sub-Saharan Africa to optimize care for HIV-infected patients.</p