Continued High Mortality Following Diagnosis of HIV-Associated Kaposi Sarcoma in East Africa in the Treat All Antiretroviral Therapy Era; 2021-2024

Despite the implementation of "Treat All" policies and new cancer guidelines in East Africa between 2021 and 2024, HIV-associated Kaposi sarcoma continues to be diagnosed at advanced stages with persistently high mortality rates, indicating an urgent need for improved prevention, early detection, and treatment strategies.

The Gist

The Unfinished Battle: A Story of Kaposi Sarcoma in East Africa

Imagine the fight against HIV as a massive, ongoing war. For years, the world has been trying to win this war using a powerful new strategy called "Treat All." The idea was simple and brilliant: give everyone with HIV the medicine they need immediately, no matter how sick they are, to stop the virus from taking over their bodies.

For most of the war, this strategy has been a huge success. It's like building a strong dam that keeps the floodwaters of the virus at bay, saving countless lives and keeping people healthy.

But there's a stubborn enemy that the dam hasn't stopped: Kaposi Sarcoma (KS).

This paper is a report card from the front lines of East Africa (Kenya, Tanzania, and Uganda) between 2021 and 2024. The researchers went out to check on the soldiers (people living with HIV) who had just been diagnosed with KS, a type of cancer caused by a virus that often hides when the immune system is weak.

Here is what they found, explained through simple analogies:

1. The "Late Arrival" Problem

Imagine a fire alarm in a building. Ideally, the alarm goes off when there's a tiny spark, and firefighters arrive to put it out before it becomes a blaze.

In this study, the researchers found that 91% of the patients were arriving at the hospital only after the fire had already engulfed the whole building.

• The Reality: When these patients were diagnosed, the cancer was already in an "advanced stage." It had spread to many parts of the body (an average of 9 different areas!).
• The Analogy: It's like waiting until the house is burning down to call the fire department. By the time the "Treat All" medicine (the water) starts working, the cancer has already done too much damage.

2. The "Broken Ladder" to Care

Even though the "Treat All" strategy exists, getting the right help for cancer is like trying to climb a ladder with missing rungs.

• The Reality: Many patients couldn't get the specific cancer drugs (chemotherapy) they needed because they were too expensive, too far away, or simply unavailable.
• The Analogy: Imagine you have a map to a life-saving treasure (the cure), but the bridge to get there is washed out. Even if you know the treasure exists, you can't reach it. The study found that even when patients did get the newer, better drugs, the survival rates didn't improve much.

3. The "Ghost Town" of Survival

The researchers tracked these patients for about a year to see how many survived. The numbers were heartbreaking.

• The Reality: Within just 3 months of diagnosis, 26% of the patients had died. By 18 months, that number jumped to 45%.
• The Analogy: It's like a race where nearly half the runners drop out before they even finish the first lap. The "Treat All" era was supposed to be a time of victory, but for these specific patients, the race remained deadly.

4. Why Haven't Things Changed?

The researchers asked: "We've had 10 years of 'Treat All' and new cancer guidelines. Why is the death rate still so high?"

They identified three main culprits:

1. The Late Diagnosis: People are still waiting too long to see a doctor. By the time they show up, it's too late.
2. The Access Gap: The "bridge" to cancer treatment is still broken for many.
3. The Limits of Medicine: The current cancer drugs are good, but they aren't perfect. They can slow the fire down, but they often can't put it out completely once it's this big.

The Bottom Line

This paper is a wake-up call. It tells us that while the "Treat All" strategy has been a hero for HIV in general, it hasn't saved everyone. Specifically, for Kaposi Sarcoma, we are still fighting a losing battle in East Africa.

The takeaway? We can't just rely on the old plan. We need:

• Better Fire Alarms: Finding the cancer earlier, before it spreads.
• Fixing the Bridge: Making sure the right cancer drugs are available and affordable for everyone.
• New Weapons: Developing stronger treatments that can actually cure the cancer, not just manage it.

Until we fix these gaps, the "Treat All" era will remain an unfinished victory for this specific group of patients.

Technical Summary

1. Problem Statement

Despite the global implementation of the World Health Organization's "Treat All" strategy (initiating antiretroviral therapy [ART] for all HIV-positive individuals regardless of CD4 count) since 2015, HIV-associated Kaposi Sarcoma (KS) remains a significant cause of morbidity and mortality in resource-limited settings. Previous research by the authors (2016–2019) indicated that KS in East Africa was frequently diagnosed at advanced stages with high mortality rates. However, the impact of broader ART implementation, the adoption of National Comprehensive Cancer Network (NCCN) guidelines for KS, and the disruptive effects of the COVID-19 pandemic on cancer care pathways remained unclear. The study addresses the critical gap in understanding whether KS control has improved in East Africa during the post-initial phase of the "Treat All" era (2021–2024).

2. Methodology

• Study Design: A prospective cohort study conducted between September 2021 and April 2024.
• Study Population: Adults (≥18 years) living with HIV (PLWH) in East Africa (Kenya, Tanzania, and Uganda) with a new diagnosis of KS.
• Study Sites: Four regions across three countries:
  • Kenya: Academic Model Providing Access to Healthcare (AMPATH) network.
  • Uganda: Infectious Diseases Institute (IDI) Kampala, Masaka Regional Referral Hospital, and Mbarara Regional Referral Hospital.
  • Tanzania: Muhimbili National Hospital, Dar es Salaam.
• Participant Identification: Consecutive PLWH with mucocutaneous lesions suspicious for KS were approached for skin biopsy. Diagnosis was confirmed via histopathology with Anti-latency-associated nuclear antigen (LANA) immunohistochemical staining. Clinical diagnosis was used only for unsafe-to-biopsy lesions (e.g., conjunctival/oral) based on consensus.
• Data Collection:
  • Baseline: Socio-demographics, HIV history, symptoms, and physical examination to determine KS extent (number of anatomic sites, lesion count, edema, ulceration) and staging (ACTG T1 vs. T0).
  • Laboratory: CD4+ T-cell counts and HIV RNA viral load at enrollment.
  • Follow-up: Vital status and chemotherapy use were tracked via in-person/phone interviews (every 3 months for the first year, then every 6 months). Community tracing was used for lost participants.
• Statistical Analysis: Survival was estimated using the Kaplan-Meier approach. Time zero was the biopsy date. Cumulative incidence of death was calculated at 3, 6, 12, and 18 months.

3. Key Contributions

• Longitudinal Update: Provides the first comprehensive update on KS staging and survival in East Africa covering the period 2021–2024, nearly a decade after the "Treat All" strategy began.
• Real-World Evidence: Captures data from a community-derived sample including referrals from facilities lacking biopsy capacity, offering a more representative view than hospital-based registries alone.
• Treatment Landscape Analysis: Documents the shift in chemotherapy regimens (moving toward paclitaxel and liposomal doxorubicin per NCCN guidelines) and correlates this with survival outcomes.
• Methodological Rigor: Achieved a very low loss-to-follow-up rate (0.6%) through active community tracing, addressing a common limitation in African cancer survival studies.

4. Key Results

• Cohort Characteristics:
  • Sample Size: 493 PLWH with newly confirmed KS.
  • Demographics: Median age 35 years; 66% male; median monthly household income $53 USD.
  • Disease Severity:
    • Median number of anatomic sites with lesions: 9 (IQR 4–12).
    • 91% presented with ACTG Stage T1 (advanced KS).
    • 83% had KS-associated edema; 58% had oral lesions.
  • Immune Status: 22% had CD4 counts <50 cells/µl; 35% had 51–200 cells/µl.
• Survival Outcomes:
  • Follow-up: Median 11 months (IQR 2.2–20).
  • Mortality: 209 deaths occurred (42.4% of the cohort). Only 3 participants were lost to follow-up.
  • Cumulative Incidence of Death:
    • 3 months: 26% (95% CI: 22–30%)
    • 6 months: 32% (95% CI: 28–36%)
    • 12 months: 39% (95% CI: 34–43%)
    • 18 months: 45% (95% CI: 40–51%)
• Treatment Patterns:
  • 55% received at least one dose of chemotherapy.
  • Regimens shifted toward paclitaxel (56%) and liposomal doxorubicin (26%), replacing older regimens like bleomycin/vincristine.
• Comparative Analysis: No significant differences in mortality were observed between countries (Kenya, Tanzania, Uganda) or across the years of diagnosis (2021–2024).

5. Significance and Conclusions

• Stagnant Outcomes: Despite nearly a decade of "Treat All" implementation and the adoption of updated NCCN guidelines, KS control in East Africa has not improved. The majority of patients still present with advanced disease, and survival rates remain critically poor, mirroring data from 2016–2019.
• Limitations of Current Strategies: The shift to more potent chemotherapy agents (paclitaxel/doxorubicin) did not translate into improved survival, suggesting that current therapies are not curative for advanced KS in this setting and that late diagnosis is the primary driver of mortality.
• Systemic Barriers: The findings highlight that HIV viral suppression alone is insufficient to prevent KS. Barriers include patient delays in seeking care, health system failures in early detection, and limited access to oncology services.
• Future Directions: The authors argue that future strategies must move beyond ART alone to include:
  • Primary prevention (e.g., HHV-8 control).
  • Novel approaches for earlier detection.
  • Timely linkage to care.
  • Increased accessibility to potent anti-KS therapies.

Conclusion: The study concludes that the "faucet" of KS incidence in sub-Saharan Africa is far from closed, and without targeted interventions specifically for KS, the high mortality burden will persist despite general HIV treatment success.