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

One in three people living with HIV (PLHIV) present with advanced HIV disease (AHD), thus with a CD4 count of <200 cells/µL, HIV stage 3 or 4 disease or children younger than five years. When starting antiretroviral treatment (ART), PLHIV with AHD have a 17% risk of dying within a year (1) Since 2017, the World Health Organization recommends a package of care for the management of AHD to reduce AIDS-related mortality. The AHD care package requires availability of CD4 testing. Identification of AHD triggers screening for Mycobacterium tuberculosis lipoarabinomannan antigen (TB LAM) and cryptococcal antigen (CrAg) by use of TB LAM and CrAg lateral flow assays (LFA). In all PLHIV with symptoms of TB, a molecular diagnostic test for TB should be performed, along with TB LAM regardless of CD4 count. Depending on results, patients should receive counselling, rapid ART initiation, treatment for identified TB or cryptococcal meningitis or preventive therapy (2).The highest burden of AHD lies in sub-Saharan Africa. Around 32%-71% of patients initiating ART there present with AHD, and up to 60% of patients who reengage in care after a treatment interruption present with AHD. Sub-Saharan Africa accounted for 68% of the global total AIDS-related deaths in 2020. Yet, the AHD care package is hardly implemented in many countries in the region (3). In a hospital in Zambia, only 39% of AHD patients had a documented CD4, TB screening was requested for 61%, and TB LAM and CrAg LFA were rarely performed (4). In facilities in Tanzania, 0% of AHD patients with TB symptoms received TB LAM, and 12% had tailored counselling. Data from Uganda, Tanzania and Nigeria show less than 20% of PLHIV receiving CrAg or TB testing. Meya et al. propose targets for the monitoring of progress; 95% of PLHIV should receive CD4 testing, 95% of those with a CD4<200 cells/µL CrAg and TB LAM testing, and 95% of those should receive appropriate (preventive) treatment (5). How countries and programmes perform against those targets has not yet been systematically described.The availability of point-of-care diagnostics is essential for the implementation of the AHD care package in primary care clinics and communities in low-and middle-income countries. However, TB LAM and CrAg LFA are not widely available in those settings and the availability of CD4 tests has reduced since the implementation of Test and Treat (3). During a TB active case finding study in rural Mozambique, the AHD care package was implemented in newly diagnosed PLHIV, ART interrupters and PLHIV with poor ART adherence. CD4 measurement and reflex CrAg LFA screening was done at a laboratory, and appointments for ART initiation were done the next day at the clinic and not in the community (6). A point-of-care test which allows for visual interpretation of a result of above or below 200 CD4 cells/µL (Omega VISITECT CD4 Advanced Disease LFA; VISITECT CD4) has become available recently. It is unknown whether it is feasible to implement the AHD care package including VISITECT CD4 during HIV/TB related community-activities, and what the outcomes are for PHLIV who received this AHD care package.I lead two studies on implementation of the AHD care package which take place during two TB triage studies in Lesotho and South Africa. During “AHD feasibility”, I will evaluate the implementation of AHD care package at rural health facilities in two phases: 1) development and evaluation of implementation tools, 2) mixed-method feasibility study during implementation (including acceptability among implementers, process compliance and early outcomes, protocol published (16) (Paper 1)). Among enrolled PLHIV, I will also evaluate risk factors for AHD and early mortality (three months after AHD detection) (Paper 2) and outcomes one year after the AHD care package (Paper 4). During “AHD community”, I will evaluate acceptability of community implementation of the AHD care package among patients and health care workers in addition to study implementers. I will also perform a stakeholder consultation with local, national and international policy makers, specialists and implementing organisations to further assess barriers and enablers of national scale-up of the AHD care package (Paper 5) Finally, I will review the literature to assess compliance of programmes implementing the AHD care package with 95-95-95 targets (Paper 6).1. Walker AS, Prendergast AJ, Mugyenyi P, Munderi P, Hakim J, Kekitiinwa A, et al. Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clin Infect Dis. 2012;55(12):1707-18.2. World Health Organization. HIV treatment: guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy: policy brief. Geneva: World Health Organization; 2017. Available from: https://apps.who.int/iris/handle/10665/255885.3. Ndlovu Z, Burton R, Stewart R, Bygrave H, Roberts T, Fajardo E, et al. Framework for the implementation of advanced HIV disease diagnostics in sub-Saharan Africa: programmatic perspectives. The Lancet HIV. 2020;7(7):e514-e20.4. Mbewe N, Vinikoor MJ, Fwoloshi S, Mwitumwa M, Lakhi S, Sivile S, et al. Advanced HIV disease management practices within inpatient medicine units at a referral hospital in Zambia: a retrospective chart review. AIDS Research and Therapy. 2022;19(1). 5. Meya DB, Tugume L, Nabitaka V, Namuwenge P, Phiri S, Oladele R, et al. Establishing targets for advanced HIV disease: A call to action. South Afr J HIV Med. 2021;22(1):12666. Izco S, Murias‐Closas A, Jordan AM, Greene G, Catorze N, Chiconela H, et al. Improved detection and management of advanced HIV disease through a community adult TB‐contact tracing intervention with same‐day provision of the WHO‐recommended package of care including ART initiation in a rural district of Mozambique. Journal of the International AIDS Society. 2021;24(8).