Addressing the Challenge of Cryptococcal Meningitis in PWH: Perspectives From Sub-Saharan Africa

Key Takeaway

• Ambition study: The liposomal amphotericin B-based regimen was noninferior to the recommended standard-of-care regimen for treating cryptococcal meningitis in people with HIV, while also being easier to administer and better tolerated.

Although HIV-related mortality has declined significantly over the past decade in Sub-Saharan Africa, mortality remains unacceptably high in the region and falls short of the FastTrack UNAIDS targets. This situation persists even in the era of accessible, effective HIV treatment and proven preventive and treatment interventions for the HIV-related opportunistic infections primarily responsible for most deaths. Cryptococcal meningitis alone accounts for 41% of acute HIV-related mortality in Sub-Saharan Africa.

For this reason, my first choice for studies presented/discussed at the 2022 IDWeek and HIV Glasgow conferences with the most relevance for healthcare professionals working in Sub-Saharan Africa is a plenary presentation given aptly by Prof Joe Jarvis, reviewing advances in the treatment of cryptococcal meningitis. 

Reduced CD4+ Cell Count Assessment Leads to Reduced Detection of Advanced HIV Disease
The 2015 World Health Organization recommendation for the immediate initiation of antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4+ cell count has been critical in moving toward Fast-Track UNAIDS goals. However, this guidance—as well as the downgrading of CD4+ cell count assessment by funding agencies (subsequently revised in 2022 to include support for the management of advanced HIV disease)—has led to a decline in patients accessing CD4+ cell count testing at baseline or as clinically indicated.

As a result, the proportion of adults with HIV in southern Africa receiving CD4+ cell count testing at the start of ART decreased from 78% in 2008 to 38% in 2017. Consequently, identifying patients with advanced HIV disease who would benefit from cryptococcal antigenemia screening has been compromised. The proportion of patients with advanced HIV disease has fallen over the years, but it remains high, with almost 25% of patients initiating ART in 2018 having advanced HIV disease, with CD4+ cell counts <200 cells/mm³. 

Further, decentralized HIV service provision in most countries in Sub-Saharan Africa means that many services are nurse-led within primary care facilities, with limited support for care navigation and a lack of access to lumbar puncture, making it difficult to ensure that patients with advanced HIV disease receive appropriate care. Even when cryptococcal meningitis is properly diagnosed, it has been difficult to treat in resource-limited settings, not the least because of a lack of access to recommended medications as well as toxicities associated with amphotericin B deoxycholate and the requirements for managing and monitoring patients receiving amphotericin B deoxycholate.

Ambition Study
Building on previous studies of liposomal amphotericin B (which showed better tolerability, a longer half-life, and good central nervous system penetration vs amphotericin B deoxycholate), the randomized, phase III Ambition study in PWH and cryptococcal meningitis compared a single IV infusion of liposomal amphotericin B followed by oral flucytosine and fluconazole for 14 days vs the standard of care (daily IV infusion of amphotericin B deoxycholate plus oral flucytosine each for 7 days followed by fluconazole for 7 days). The results demonstrated that the liposomal amphotericin B-based regimen was noninferior to the standard-of-care regimen while also being easier to administer and better tolerated. 

In his plenary presentation, Dr. Jarvis also reviewed ongoing research on cryptococcal meningitis management, highlighting several key points:

• Other proven interventions that save lives should be used at scale; these include screening for cryptococcal antigenemia with appropriate preemptive treatment.  
• Timely HIV testing, linkage to care, rapid ART initiation, and continuous retention in care remain urgent priorities (limiting the number of patients coming in and out of care).
• New drugs and approaches are under clinical investigation. 

Long-Acting ART
In addition to the cryptococcal meningitis plenary session, I also want to highlight that several presentations at both IDWeek and HIV Glasgow 2022 continued to confirm the efficacy and tolerability of long-acting (LA) injectable cabotegravir plus rilpivirine, administered monthly or bimonthly, as a switch regimen for patients with viral suppression on their current ART and with no known resistance to these antiretroviral drugs. Notably, in the “resource-rich” settings included in the analyses, rates of treatment failure were very low. But there is not much data coming out of resource-limited settings on the use of LA ART regimens, although WHO guidelines now recommend LA cabotegravir for HIV pre-exposure prophylaxis (PrEP) and a voluntary licensing agreement between the drug manufacturer and the Medicine Patent Pool for LA cabotegravir, as PrEP was signed in July 2022, a critical step to facilitate access. 

Your Thoughts?
If you provide HIV care services in Sub-Saharan Africa or other resource-limited settings, what are your thoughts on the most relevant studies presented at IDWeek and HIV Glasgow 2022? Join the discussion and share your experiences by posting a comment.