Implementation and outcomes of the advanced HIV disease care package in high HIV/TB burden settings

Advanced HIV disease (AHD), defined in adults as a CD4 count below 200 cells/μl or a World Health Organization (WHO) stage 3 or 4 condition, drives mortality from HIV. A package of care, including point-of-care diagnostics, treatment and prophylaxis for opportunistic infections exists but is poorly available in health facilities, and absent in the community, in high HIV/TB burden settings. I aimed at assessing the feasibility of its implementation at community level. Studies were embedded in two TB triage trials in Lesotho and South Africa, recruiting 1,300 individuals near-facility and 20,000 during door-to-door community-based TB screening. The AHD care package was provided to enrolled PWH. With mixed-methods, I assessed the feasibility of near-facility and community implementation of the AHD care package. In presumptive TB-cases presenting near-facility AHD was prevalent (35-56%), and implementation of the AHD care package feasible. In the community, 2.9% of PWH had AHD. Community-level implementation of the AHD care package was acceptable, but conditional to availability of accurate point-of-care CD4 test, prophylactic treatment, solid referral systems and dedicated staff. In three studies, I evaluated a novel semi-quantitative CD4 test, the VISITECT CD4 Advanced Disease (VISITECT). VISITECT sensitivity was good, but specificity suboptimal compared to flow cytometry. Acceptability of VISITECT compared to PIMA CD4 was low in healthcare workers, due to perceived low accuracy, and not producing a numeric CD4 value. I evaluated the performance of point-of-care TB-LAM testing on urine in PWH with presumptive TB. TB-LAM improved the diagnostic yield 1.6-fold compared to a composite TB reference, but the therapeutic yield only 1.2-fold. Positive TB-LAM results, when Xpert MTB/RIF was negative, were negatively associated with TB treatment initiation. Qualitatively, I showed that the term AHD was often unknown to PWH in South Africa. PWH developed AHD following: i) missed opportunities to (re)-engage in care, ii) emotional stress and impaired mental health, iii) alternative beliefs about medicines and health and iv) stigma, denial and non-disclosure. Strengths of the thesis include the variety of methods used and rigorous data collection. Limitations include the lack of longer-term outcomes of PWH with AHD. I showed that AHD is prevalent, among presumptive TB patients and in the community. Community-based implementation of the AHD care package is relevant and depends on the availability of an accurate and acceptable point-of-care CD4 test. Community-led AHD management may be necessary to face current global funding challenges for HIV.