Acquired immunodeficiency syndrome (AIDS) is a severe immunodeficiency disease caused by human immunodeficiency virus (HIV) infection, which predisposes patients to various malignancies (1). Acute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML), characterized by a chromosomal translocation t(15;17)(q22;q12), resulting in the formation of the PML-RARA fusion gene. This fusion protein blocks cell differentiation and inhibits apoptosis, representing the primary molecular mechanism underlying APL (2, 3). APL typically affects young and middle-aged individuals, with a mean onset age of 44 years. It accounts for 10% to 15% of AML cases, with an incidence rate of approximately 0.23 per 100,000 (2). As a distinct AML subtype, APL presents unique clinical features and treatment responses. When AIDS and APL occur simultaneously, the complexity of diagnosis and treatment increases significantly, posing significant clinical challenges.

A 46-year-old male patient, living with HIV infection for over a decade, had not received treatment for four consecutive years after his diagnosis ( Figure 1 ). The patient self-reported that in 2017, diagnostic findings confirmed progression to the AIDS stage, prompting initiation of antiretroviral therapy (ART). During this period, the patient underwent viral load and CD4⁺ T-cell count monitoring at the local CDC in their hometown; however, specific reports are unavailable. The patient self-reported a CD4⁺ T-cell count of approximately 300 cells/μL during ART, still indicating incomplete immune reconstitution. The current treatment regimen comprises tenofovir (TDF), lopinavir/ritonavir (LPV/r), and lamivudine (3TC). In December 2023, the patient presented with dizziness lasting over two months, accompanied by fever, cough, and sputum for two days. A routine blood test revealed a 28% blast cell population in peripheral blood, leading to his immediate hospitalization. Complete bone marrow analysis indicated an increase in promyelocytes, with visible azurophilic granules and Auer rods, suggestive of APL ( Table 1 ) ( Figures 2A, B ). The diagnosis was confirmed by flow cytometry and positive PML-RARA fusion gene results ( Figures 2C, D ).

Upon admission, the patient’s CD4⁺ T-cell count was measured at 329.6 cells/μL (indicating moderate immunosuppression), accompanied by severe pulmonary infection, along with prolonged prothrombin time and activated partial thromboplastin time due to APL, elevated D-dimer levels, granulocytopenia, thrombocytopenia, anemia, and other signs suggestive of disseminated intravascular coagulation (4). Given that the patient was stratified as low-risk for APL prognosis, Treatment was initiated with all-trans retinoic acid (ATRA) (25mg·m^-2·d^-1) to induce differentiation (while deferring arsenic trioxide (ATO) (0.16mg·kg^-1·d^-1) due to the severe lung infection). Simultaneously, supportive therapies were administered, including anti-infective measures, bleeding prevention, multiple plasma and platelet transfusions, and anti-HIV treatment. The patient subsequently developed liver dysfunction and leukocytosis (white blood cell count exceeding 10×10⁹/L), prompting adjustments in treatment strategy. Concurrently, the patient received comprehensive supportive care comprising: cefotaxime 2.0g IV q12h, piperacillin-sulbactam 4.5g IV q8h (escalated from cefotaxime based on clinical suspicion of extended-spectrum beta-lactamase (ESBL)-producing pathogens), and micafungin 100mg IV qd for antimicrobial prophylaxis; bleeding prevention measures; multiple fresh frozen plasma and platelet transfusions; and antiretroviral therapy for HIV comanagement. During the treatment course, the patient developed hepatotoxicity accompanied by leukocytosis (white blood cell count >10×10⁹/L). Therapeutic interventions were escalated with hydroxyurea 0.5g PO bid (days 8–10 post-diagnosis) and idarubicin 8mg/m² IV daily (days 9–11 post-diagnosis) for leukocyte cytoreduction, supplemented by hepatoprotective agents including ursodeoxycholic acid and glutathione infusion. Hydroxyurea (0.5g bid 8–10 days in the course of the disease) and idarubicin (8mg·m^-2·d^-1 Days 9–11 of the course of disease) were used to reduce leukocytosis, and liver protection measures were implemented. Follow-up exams showed improvement in the lung infection and normalization of liver function, with bone marrow tests performed on day 20 indicating partial remission.

The patient then began ATO (0.16mg·kg^-1·d^-1) intravenous chemotherapy combined with oral ATRA (25mg·m^-2·d^-1), continuing with the first treatment course for induction therapy. During this phase, he experienced fever again, and chest CT revealed patchy and nodular density shadows in both lungs. A regimen of meropenem and micafungin was administered, improving the infection, with serial monitoring of CD4⁺ T-cell counts revealing a nadir of 148.4 cells/μL on day 26 of the disease course. On day 33 of the disease course, a follow-up evaluation was performed. Continued induction therapy led to morphological remission in bone marrow. After another course of ATO (0.16mg·kg^-1·d^-1) and ATRA (25mg·m^-2·d^-1), the PML-RARA fusion gene turned negative, and the patient achieved complete remission (CR). At the end of the second treatment course, follow-up testing revealed a CD4⁺ T-cell count of 369.9 cells/μL. Currently, the patient is undergoing consolidation therapy, showing an increased CD4⁺ T-cell count, persistent fusion gene negativity, and only mild anemia.

APL presents with severe clinical manifestations, with high risks of bleeding and embolism during onset and induction therapy, potentially leading to fatal outcomes. Over the past three decades, the standardized clinical use of ATRA and ATO has transformed APL into a curable leukemia without the need for hematopoietic stem cell transplantation (5, 6).

A review of 11 previously reported AIDS-related APL cases (7–16) highlights that most patients achieved remission with ATRA alone or in combination with chemotherapy (anthracyclines or arsenic) ( Table 2 ). Only one high-risk patient succumbed to severe disseminated intravascular coagulation. Long-term remission was achieved in most cases through consolidation and maintenance therapy. One patient who discontinued ATRA due to nausea relapsed one year later but achieved a second CR following salvage therapy with ATO (12).

Given the high mortality associated with APL, immediate ATRA treatment is recommended based on cytological and clinical criteria, while awaiting genetic confirmation (3, 4). In this case, the patient’s severe lung infection and liver dysfunction posed risks for initial ATO combination therapy. Since 1986, Shanghai Ruijin Hospital has successfully utilized ATRA-induced differentiation therapy for APL, with a CR rate of 75% to 85% for ATRA alone (17). Therefore, we opted for ATRA monotherapy during the early treatment phase. After the infection and liver function improved, ATO was added, and ATRA was continued for one week, achieving morphological remission, as observed in two other cases treated with ATRA alone (7, 8).

In the consolidation phase, we continued ATRA combined with ATO. Given the patient’s history of HIV and long-term ART, we carefully evaluated whether this chemotherapy regimen might interfere with his HIV treatment. Previous studies indicate that while ATRA upregulates HIV mRNA transcription in infected human HL-60 cell lines, it does not increase viral replication due to blocked HIV mRNA translation and replication. This mechanism ultimately leads to the apoptosis of HIV-infected cells, reducing the proviral DNA load in a dose-dependent manner (18). Furthermore, ATRA significantly decreased viral replication in primary lymphocytes from HIV-infected patients, suggesting it may also serve as a therapeutic agent against HIV infection (19).

Research from the Chinese Academy of Sciences and Sun Yat-sen University showed that ATO specifically activates latent viral reservoirs without inducing excessive inflammation. In a simian immunodeficiency virus (SIV) model, ATO combined with ART significantly delayed viral rebound post-drug withdrawal, with some monkeys showing no viral rebound after 80 days (compared to 22 days for ART alone). ATO reduced viral reservoirs and enhanced virus-specific immune responses. Moreover, ATO downregulated the expression of CD4 and CCR5 receptors on CD4⁺ T-cells, essential for HIV entry, thus inhibiting new rounds of viral infection (20).

In conclusion, initiating ATRA treatment based on clinical and morphological criteria can significantly improve outcomes in APL patients, even in complex cases like this. Individualized treatment tailored to the patient’s condition may lead to better efficacy. For consolidation and maintenance therapy, further case studies and multicenter clinical trials are needed to confirm whether ATRA combined with ATO is the optimal approach. Continuous optimization of treatment protocols is essential to improve patient outcomes and quality of life.