Advanced HIV disease: A review of diagnostic and prophylactic strategies

Abstract

Background Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) ‘test‐and‐treat’ strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first‐line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point‐of‐care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. Methods We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. Results While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non‐sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource‐poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. Conclusions Despite progress with HIV treatment and prevention, a persistent 20%–30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV‐related morbidity and mortality. Investment in the development of additional POC or near‐bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same‐day results. However, in real‐world scenarios, people with AHD have multiple comorbidities and imperfect follow‐up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

Advanced HIV Disease at Antiretroviral Therapy Initiation and Treatment Outcomes Among Children and Adolescents Compared to Adults Living With HIV in Kinshasa, Democratic Republic of the Congo

“…This analysis explored the prevalence of AHD at ART initiation and related mortality among PLHIV in Kinshasa, DRC, and associated age inequalities. Our findings reveal that AHD at treatment initiation among PLHIV was high, at 32%, which is consistent with global estimates 10 , 11 and a similar study in South Africa. 12 In partial support of our first hypothesis, AHD was more common among adolescents, males, and those who began treatment before 2015.…”

“…8,9 However, this positive news may mask an enduring burden of advanced HIV disease (AHD), defined as having CD4 cell count < 200 cells/μL or WHO clinical stages III and IV. 10 Approximately 30% of PLHIV globally have AHD 10,11 ; these patients are at increased risks for mortality (even after treatment initiation), opportunistic infections, and higher treatment costs than PLHIV without AHD. [10][11][12] Late linkage to care, delayed ART initiation, ART failure, and poor in-care retention are the main driving factors of AHD.…”

“…10 Approximately 30% of PLHIV globally have AHD 10,11 ; these patients are at increased risks for mortality (even after treatment initiation), opportunistic infections, and higher treatment costs than PLHIV without AHD. [10][11][12] Late linkage to care, delayed ART initiation, ART failure, and poor in-care retention are the main driving factors of AHD. 11,13 The high prevalence of these factors in low-income countries exposes all PLHIV to AHD; however, with lower ART coverage than adults, children, and adolescents living with HIV (CALHIV) in these settings might be at a disproportionately higher risk of initiating ART with AHD compared to adults.…”

“…[10][11][12] Late linkage to care, delayed ART initiation, ART failure, and poor in-care retention are the main driving factors of AHD. 11,13 The high prevalence of these factors in low-income countries exposes all PLHIV to AHD; however, with lower ART coverage than adults, children, and adolescents living with HIV (CALHIV) in these settings might be at a disproportionately higher risk of initiating ART with AHD compared to adults. 14,15 PLHIV in the DRC experience higher levels of AHD compared to global averages.…”

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication

“…The last updated World Health Organization (WHO) report indicated that globally about 39.0 million people acquired HIV-1 and 630,000 people died from HIV-1-dependent problems at the end of 2022 [5]. Furthermore, HIV-1/AIDS provokes opportunistic infections including tuberculosis, cryptococcal infection, histoplasmosis, and severe bacterial infections; hepatitis B, and C co-infections [6][7][8]; and comorbidities such as cardiovascular, kidney, and liver disorders and cancer [9]. In the near future, COVID-19 and monkeypox virus infections could be possible challenges for clinicians and people with HIV-1 [10,11].…”