Abstract
Immune checkpoint inhibitors (ICIs) are a standard treatment for advanced non-small-cell lung cancer (NSCLC), but limited data exist regarding their use in patients with HIV-positive. This study evaluated the efficacy and safety of ICI-based therapy in this population. In this single-center, comparative study, 18 patients with treatment-naive advanced NSCLC with HIV (experimental group) and 40 HIV-negative controls (control group) received 4–6 cycles of tislelizumab plus platinum-based chemotherapy, followed by tislelizumab maintenance until disease progression or unacceptable toxicity. A higher incidence of tuberculosis was observed in the experimental group compared with the control group (33.3 vs. 20.0%). The objective response rate was 77.8% [95% confidence interval (CI): 56.5–99.1] in the experimental group and 77.5% (95% CI: 64–91) in the control group (P = 0.981). The 6-month progression-free survival rate was 83.3% (95% CI: 64.3–99.9) for the experimental group and 82.5% (95% CI: 70.2–94.8) for the control group (P = 0.227). The 6-month overall survival rate was 88.9% (95% CI: 72.8–99.9) in the experimental group and 97.5% (95% CI: 92.4–99.9) in the control group (P = 0.192). The incidences of grade 3 or higher adverse events were 38.9 and 32.5% in the experimental and control groups, respectively. One patient in the experimental group died due to a serious opportunistic infection. Immunotherapy combined with chemotherapy showed comparable efficacy and safety in patients with advanced NSCLC irrespective of HIV status. Patients with HIV-positive had a higher tendency for opportunistic infections, including tuberculosis.
Keywords: chemotherapy, HIV-positive non-small-cell lung cancer, immunotherapy, tislelizumab
Background
In the era of antiretroviral therapy (ART) and the aging population, malignant tumors are the leading cause of death in patients with HIV infection [people living with HIV (PLHIV)], with lung cancer being one of the malignancies with the highest mortality rate among non-AIDS-induced malignancies [1,2]. Previous studies have shown that HIV infection is a high-risk factor for lung cancer [3,4] reported that patients with HIV infection complicated with lung cancer had a lower cure rate (6.5 vs. 27.7%; P < 0.001). Other studies also showed that the overall median survival period of patients with HIV-positive non-small-cell lung cancer (NSCLC) was 12.4 months, while that of ordinary patients with NSCLC was 22.8 months. Moreover, the 2-year survival rate (P = 0.028) and 3-year survival rate (P = 0.014) of patients with HIV-positive NSCLC were significantly lower, and the HIV status was an independent risk factor for poor prognosis after controlling for other factors [5].
The treatment pattern of immune checkpoint inhibitors (ICIs), represented by PD-1 inhibitors and PD-L1 inhibitors, combined with chemotherapy, has become one of the standard treatments for patients with advanced NSCLC and can be considered a breakthrough in the treatment of NSCLC in the past decade. The efficacy and safety of ICIs in combination with platinum-based doublet therapy in advanced NSCLC have been increasingly validated [6]. On the basis of phase III clinical trial data, ICIs in combination with chemotherapy have been approved as an important treatment option for patients with advanced NSCLC in some countries and regions worldwide [7,8], including pembrolizumab, camrelizumab, sindilimab, tislelizumab, atezolizumab, and some other ICIs; however, because ICIs function by suppressing immune tolerance and reactivating effective immune responses, HIV-infected individuals may exhibit insufficient responses to tumor immunotherapy because of HIV-associated chronic immune deficiency and ART disrupting immune parameters [9]. Therefore, PLHIV patients with concomitant malignant tumors are often excluded from large clinical studies. Clinical data on the use of ICIs in HIV-positive patients with advanced NSCLC are also limited; however, some clinical study data showed that ICIs have certain efficacy and safety in patients with HIV-positive NSCLC. Assoumou et al. [10] analyzed the use of ICIs in 65 patients with HIV-positive lung cancer, with an 18-month survival rate of 36.4%, which was much lower than that of patients with HIV-positive melanoma (83.3%) and patients with HIV-positive Hodgkin’s lymphoma (88.9%). Bender Ignacio et al. [11] have demonstrated the feasibility of chemotherapy, immunotherapy, and radiotherapy for PLHIV with malignant tumors, while also highlighting the need for further investigation into whether such patients possess sufficient immune reserves to withstand the challenges of antitumor treatment. Therefore, further discussion of the potential benefits of combination therapy with ICIs in patients with HIV-positive and consideration of its treatment safety is necessary.
Although an increasing number of researchers are paying attention to the benefits of immunotherapy for this special population, most studies are retrospective [12–14], with limited prospective research [15]. Therefore, the efficacy and safety of immunotherapy in patients with HIV-positive NSCLC require further investigation. This study was a prospective, controlled study that enrolled HIV-positive patients with unresectable locally advanced or advanced NSCLC and compared them with HIV-negative patients with unresectable locally advanced or advanced NSCLC to investigate whether the combination therapy of tislelizumab plus platinum-based therapy could provide benefits in the first-line treatment of HIV-positive patients with unresectable locally advanced or advanced NSCLC.
Methods
Study design and patients
This single-center, comparative clinical study was conducted with approval from the institutional ethics committee and written informed consent from all patients. HIV-positive and HIV-negative patients with NSCLC were assigned to the experimental and control groups, respectively. All enrolled patients were aged between 18 and 75 years old, pathologically diagnosed and classified as stage IIIC–IV according to the American Joint Committee on Cancer (AJCC) eighth edition staging system, negative for EGFR, ALK, and ROS1 target genes, no prior systemic anticancer therapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, adequate bone marrow reserve capacity (neutrophil count ≥ 1500/mm³, platelet count ≥ 100 000/mm³, hemoglobin count ≥ 6 g/dl), adequate liver function (bilirubin level ≤ 1.5 times the upper limit of the reference range, alanine transaminase and aspartate transaminase ≤ 1.5 times the upper limit of the reference range), and adequate kidney function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 60 ml/min). For patients with HIV-positive who have undergone ART treatment and have an HIV RNA viral load less than 200 copies/ml, regardless of CD4+ T-cell counts. Patients with HIV-negative referred to those testing negative for HIV antibodies.
Treatments
Both the experimental group and the control group received treatment with tislelizumab (200 mg) combined with platinum-based chemotherapy. The chemotherapy regimen was as follows: for squamous cell carcinoma, albumin-bound paclitaxel (260 mg/m2), combined with cisplatin (75 mg/m2) or carboplatin (area under the curve, 5 mg/ml/min); for nonsquamous cell carcinoma, pemetrexed disodium (500 mg/m²) was used in combination with cisplatin (75 mg/m2) or carboplatin (area under the curve, 5 mg/ml/min). Administer once every 3 weeks. After 4–6 cycles, switch to maintenance therapy with tislelizumab (200 mg) until disease progression or intolerable side effects occur. The maximum duration of tislelizumab treatment is 2 years.
Assessments and endpoints
Efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse reactions were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The endpoint is objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
Statistical analysis
Patients with complete treatment data were included in the analysis. SPSS 27.0 software was used to perform t tests, χ2 tests, and Kaplan–Meier survival curve analysis. Proportions were compared using χ2 tests or Fisher’s exact probability test, with P less than 0.05 indicating statistically significant differences. GraphPad Prism 10.1.2 was used to plot charts showing trends in CD4+ T-cell counts.
Results
Baseline characteristics of the study population
A total of 60 patients were enrolled between 1 January 2023 and 28 February 2025, including 20 patients with HIV-positive and 40 patients with HIV-negative. Two patients with HIV-positive were lost to follow-up and excluded from the study, resulting in a final enrollment of 18 patients with HIV-positive. The median follow-up duration in the experimental group was 8.12 months (range: 6.43–26), and in the control group, it was 13.45 months (range: 7.8–26). The study flowchart is shown in Fig. 1.
Fig. 1.
Flowchart of the study.
Baseline characteristics were similar between the experimental and control groups. The median age was 60 and 59 years, with 83.3 vs. 87.5% males, 77.8 vs. 87.5% current or former smokers, 66.7 vs. 60% with an ECOG Performance Status of 1, 77.8 vs. 72.4% with squamous cell carcinoma, and 88.9 vs. 85.0% with stage IV disease, respectively, as detailed in Table 1. All patients with HIV-positive underwent HIV RNA viral load monitoring at baseline. Among them, 18 patients had HIV RNA levels less than 200 copies/ml, and 17 patients had HIV RNA levels less than 50 copies/ml. Regarding CD4+ T-cell counts, 27.8% (n = 5) had counts less than 200 cells/μl, while the remaining patients had counts greater than or equal to 200 cells/μl. Noteworthy, patients with HIV-positive had a higher proportion of tuberculosis history (33.3 vs. 20%).
Table 1.
Baseline characteristics of experimental group and control group
| Baseline characteristics | Experimental group (HIV-positive), n = 18 | Control group (HIV-negative), n = 40 |
|---|---|---|
| Age (years), median | 60 (34–75) | 59 (35–75) |
| Gender, n (%) | ||
| Male | 15 (83.3) | 35 (87.5) |
| Female | 3 (16.7) | 5 (12.5) |
| Smoking status, n (%) | ||
| Current or former smokers | 14 (77.8) | 35(87.5) |
| Never | 4 (22.2) | 5(12.5) |
| ECOG PS, n (%) | ||
| 0 | 6 (33.3) | 16(40) |
| 1 | 12 (66.7) | 24(60) |
| Histology, n (%) | ||
| Squamous | 14 (77.8) | 29 (72.5) |
| Adenocarcinoma | 4 (22.2) | 9 (22.5) |
| Other, n (%) | – | 2 (5) |
| Clinical stage at study entry | ||
| ⅢC | 2 (11.1) | 6 (15) |
| ⅣA/ⅣB | 16 (88.9) | 34 (85) |
| HIV RNA viral load (copies/ml) | ||
| <50 | 17 (94.4%) | – |
| ≥50 | 1 (5.6%) | – |
| Baseline CD4+ T-cell counts (cells/μl) | ||
| ≤200 | 4 (22.2) | 1 (2.5) |
| 200–400 | 7 (38.9) | 8 (20) |
| ≥400 | 7 (38.9) | 31 (77.5) |
| Baseline CD4+ T-cell counts: CD8+ T-cell counts ratio | ||
| ≥0.43 | 6 (33.3) | 1 (2.5) |
| <0.43 | 12 (66.7) | 39 (97.5) |
| History of tuberculosis | ||
| Yes | 6 (33.3) | 8 (20) |
| No | 12 (66.7) | 32 (80) |
ECOG PS, Eastern Cooperative Oncology Group Performance Status.
Efficacy
At the end of follow-up, the ORR was 77.8% [95% confidence interval (CI): 56.5–99.1%] in the experimental group and 77.5% (95% CI: 64–91%) in the control group, with no statistically significant difference between the two groups (P = 0.981). The 6-month DoR was 55.6% (95% CI: 30.1–81%) in the experimental group and 65% (95% CI: 49.6–80.4%) in the control group, with no statistically significant difference between groups (P = 0.495) (Table 2).
Table 2.
The best response of tumors in the experimental group and the control group
| Overall response | Experimental group (HIV-positive), n = 18 | Control group (HIV-negative), n = 40 | P value |
|---|---|---|---|
| CR, n (%) | 0 (0) | 0 (0) | – |
| PR, n (%) | 14 (77.8) | 31 (77.5) | – |
| SD, n (%) | 4 (22.2) | 8 (20) | – |
| PD, n (%) | 0 (0) | 1 (2.5) | – |
| ORR (95% CI) | 77.8 (56.5–99.1) | 77.5 (64–91) | 0.981 |
| 6-month DoR (95% CI) | 55.6 (30.1–81) | 65(49.6–80.4) | 0.495 |
CI, confidence interval; CR, complete response; DoR, duration of response; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease.
At the end of follow-up, median progression-free survival (mPFS) was not yet reached. The 6-month PFS rate was 83.3% (95% CI: 64.3–99.9%) in the experimental group and 82.5% (95% CI: 70.2–94.8%) in the control group, with no significant statistical difference (P = 0.227) (Fig. 2a). Median overall survival (mOS) was not yet reached. The 6-month OS rate was 88.9% (95% CI: 72.8–99.9%) in the experimental group and 97.5% (95% CI: 92.4–99.9%) in the control group. There was also no significant statistical difference(P = 0.192) (Fig. 2b).
Fig. 2.
Clinical outcomes in experimental group patients with chemotherapy combined with immunotherapy versus control group patients with chemotherapy combined with immunotherapy. (a) Kaplan–Meier estimates for PFS. (b) Kaplan–Meier estimates for OS. CI, confidence interval; OS, overall survival; PFS, progression-free survival.
Effect of treatment on CD4+ T-cell counts
The median CD4+ T-cell counts in peripheral blood at baseline were 315.5 [interquartile range (IQR): 466.75–199.5] in the experimental group, and 508 (IQR: 686.25–442.25) in the control group. After two treatment courses, the CD4+ T-cell counts were 301 (IQR: 518–142.5) and 590 (IQR: 776–475) in the experimental group and control group, respectively. After four treatment courses, the CD4+ T-cell counts were 315 (IQR: 520.5–191) and 494 (IQR: 705–380.5), and after six treatment cycles, the counts were 220 (IQR: 328.75–131.5) and 399.5 (IQR: 531.25–251), respectively. Chemotherapy combined with immunotherapy resulted in fluctuations in CD4+ T-cell counts in both the experimental and control groups; however, as shown in Table 3 and Fig. 3, this trend did not appear to show significant differences.
Table 3.
CD4+ T-cell counts after treatment with 0–6 cycles of chemotherapy combined with immunotherapy
| CD4+ T-cell counts (cells/μl) | Experimental group (HIV-positive), n = 18 | Control group (HIV-negative), n = 40 |
|---|---|---|
| Baseline median (IQR) | 315.5 (IQR: 466.75–199.5) | 508 (IQR: 686.25–442.25) |
| Two courses of treatment, median (IQR) | 301 (IQR: 518–142.5) | 590 (IQR: 776–475) |
| Four courses of treatment, median (IQR) | 315 (IQR: 520.5–191) | 494 (IQR: 705–380.5) |
| Six courses of treatment, median (IQR) | 220 (IQR: 328.75–131.5) | 399.5 (IQR: 531.25–251) |
IQR, interquartile range.
Fig. 3.
Exploratory analysis of CD4+ T-cell counts in peripheral blood after treatment with 0–6 cycles.
Treatment-related adverse effects
Treatment-related adverse effects were evaluated in 18 patients in the experimental group and 40 patients in the control group, as shown in Table 4. The incidence of treatment-related adverse events of any grade was 83.3% (15/18) in the experimental group and 90% (36/40) in the control group. The incidence of grade 3 or higher adverse events was 38.9% (7/18) in the experimental group and 32.5% (13/40) in the control group. Chemotherapy-related adverse reactions primarily include neutropenia, anemia, thrombocytopenia, fatigue, and neurotoxicity; immune therapy–related adverse reactions primarily include skin toxicity, pulmonary toxicity, and endocrine gland toxicity death due to treatment-related adverse reactions. There was no significant difference in the incidence of adverse reactions regardless of HIV status. In addition, no further impairment of liver and kidney function was observed in HIV-positive patients receiving antitumor therapy in combination with ART; however, during the study, one patient in the experimental group (HIV-positive) died from severe opportunistic infection, which is noted here for special attention.
Table 4.
Treatment-related adverse events
| Adverse events, n (%) | Experimental group (HIV-positive), n = 18 All grade |
Grade ≥ 3 | Control groups (HIV-negative), n = 40 All grade |
Grade ≥ 3 |
|---|---|---|---|---|
| Any | 15 (83.3) | 7 (38.9) | 36 (90) | 13 (32.5) |
| Chemo-related adverse events | ||||
| Neutropenia | 10 (55.6) | 5 (27.8) | 21 (52.5) | 6 (15) |
| Anemia | 9 (50) | 0 (0) | 15 (37.5) | 3 (7.5) |
| Platelet count decreased | 6 (33.3) | 1 (5.6) | 11 (27.5) | 4 (10) |
| Neurological toxicity | 3 (16.7) | 1 (5.6) | 14 (35) | 1 (2.5) |
| Vomiting/nausea | 5 (27.8) | 0 (0) | 15 (37.5) | 0 (0) |
| Fatigue | 8 (44.4) | 0 (0) | 16 (40) | 0 (0) |
| AST/ALT/blood bilirubin increased | 1 (5.6) | 0 (0) | 5 (12.5) | 0 (0) |
| Rash | 2 (11.1) | 0 (0) | 3 (7.5) | 0 (0) |
| Creatinine increased | 2 (11.1) | 0 (0) | 1 (2.5) | 0 (0) |
| Constipation | 3 (16.7) | 0 (0) | 3 (7.5) | 0 (0) |
| Immune-related adverse events | ||||
| Skin toxicity | 1 (5.6) | 0 (0) | 1 (2.5) | 1 (2.5) |
| Lung toxicity | 1 (5.6) | 1 (5.6) | 1 (2.5) | 0 (0) |
| Endocrine glands toxicity | 1 (5.6) | 0 (0) | 1 (2.5) | 1 (2.5) |
| Cardiotoxicity | 0 (0) | 0 (0) | 1 (2.5) | 0 (0) |
| Liver toxicity | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Any event leading to death | 1 (5.6) | 0 (0) | ||
ALT, alanine transaminase; AST, aspartate transaminase.
Discussion
Our study investigates whether HIV status affects the efficacy and safety of ICI-based antitumor therapy in patients with advanced NSCLC. Over the past 25 years, ART has significantly increased the life expectancy of PLHIV. Researchers have found that, regardless of socioeconomic status, standardized ART treatment has improved life expectancy and reduced mortality rates among HIV-infected patients [16,17]. On the basis of the background that PLHIV achieves longer survival with effective viral control, it is necessary to further explore more effective antitumor methods for HIV-positive patients with malignant tumors. Currently, there are few prospective studies evaluating the efficacy and safety of immunotherapy combined with chemotherapy in patients with HIV-positive, and many large clinical trials have excluded this patient population. Therefore, our study aimed to provide more evidence for clinical decision-makers and researchers in this field.
In the early period of successful ICIs treatment for solid tumors, researchers were actively exploring the efficacy and safety of ICIs in antitumor therapy for patients with chronic viral infections. Gonzalez-Cao et al. [18] treated 20 patients with PLHIV-associated malignancies with durvalumab, including 14 patients with NSCLC, and showed that for the evaluable 16 patients, 25% achieved partial response (all NSCLC) and 31% achieved SD with no grade 3 or higher adverse events, which provided confidence in the use of ICIs for PLHIV-complicated malignancies. In a meta-analysis that included 25 patients with HIV-positive NSCLC, the objective remission rate with ICIs monotherapy was 30% [19]. In recent years, a good number of researchers have spoken out in favor of HIV infection as a specific group that should not be easily excluded from clinical studies. In a study of the use of ICIs in patients with HIV, hepatitis B virus, and hepatitis C virus, which showed that viral status did not have a clear impact on their efficacy and adverse effects, and no activation of the virus was observed, the authors called for the need for relevant clinical studies to be more cautious in excluding such patients [14]. Another retrospective study showed that in 66 PLHIV and 56 patients with non-HIV, the incidence of more than grade 3 adverse reaction rates after treatment with ICIs was 11 and 13%, respectively, and after multifactorial adjustment, baseline CD4+ T-cell counts were found not to influence the incidence of treatment-related adverse reactions, and the authors recommended that CD4+ T-cell counts thresholds should be carefully reviewed in future clinical trials to avoid exclusion of Unnecessary study subjects [20]. Some studies have found that the use of ICIs has a very limited effect on HIV reservoir and antiviral immune response in patients with PLHIV [21]. These findings provide ideas and confidence in the use of immune-combination therapy in our trial participants.
The results of our study analyzed 18 patients with HIV-positive (experimental group) and 40 patients with non-HIV (control group) treated with tislelizumab in combination with platinum-containing chemotherapy, followed by tislelizumab maintenance therapy. The results showed an ORR of 77.8% (95% CI: 56.5–99.1%) in the experimental group and 77.5% (95% CI: 64–91%) in the control group (P = 0.981). This result is similar to the objective remission rate of 74.2 or 73.9% in the combination therapy group in the general population in the RATIONALE-307 [22], and slightly higher than the ORR in the combination therapy group in the RATIONALE-304 [23], which may be related to the fact that more patients with squamous cell carcinoma were enrolled in the present study than those with nonsquamous cell carcinoma. Because of the short follow-up period, only 6-month PFS and OS results are currently available, and we found no significant survival differences between the two groups. This supports the conclusion that patients with HIV-positive NSCLC can benefit from ICIs therapy.
A large proportion of clinical experts have expressed concern about whether ICIs cause immune depletion and viral replication in patients with HIV-positive, but current studies have concluded that the effects of ICIs on CD4+ T cell and viral load are not clinically significant [24,25]. The phenomenon we observed was that, regardless of HIV status, CD4+ T-cell counts in the peripheral blood of both groups tended to fluctuate as the chemotherapy combined with the immunotherapy regimen progressed, with some cycles showing an upward change, and no significant differences were seen between the two groups. By reviewing previous studies, we found that elevated CD4+ T-cell counts in peripheral blood were associated with both chemotherapy and immunotherapy efficacy. Either chemotherapy or immunotherapy showed better efficacy or PFS in patients with malignant tumors with higher CD4+ T-cell counts [26–28].
In terms of adverse effects, we observed ICIs combination chemotherapy with hematological toxicity as the main adverse reaction in both the experimental group and the control group, and the two groups were close to each other in terms of incidence, which was similar to the findings of the RATIONALE-307 [22], and we did not observe any unexpected adverse events in the experimental group. One patient in the experimental group died during follow-up because of a complication of a serious opportunistic infection and not due to treatment, which event is inevitable in the management of HIV therapy. It further suggests that more attention should be paid to the prevention of opportunistic infections in the management of patients with HIV-positive NSCLC.
This study also provided important data in that the prevalence of tuberculosis was significantly higher in the experimental group than in the control group (33.3 vs. 20%), and most of these patients developed tuberculosis after HIV infection. The incidence of concomitant tuberculosis in patients with HIV-infected varies significantly with geography and economy, about 3.49 per 100 person-years in sub-Saharan Africa [29], and 1.03 per 1000 person-years in Europe [30], but the occurrence of tuberculosis is closely associated with all-cause mortality in this group of patients [31], and the prognosis of this group of patients may be even worse if they are unfortunate enough to develop tumors. So active attention to this group of patients is also an important research direction.
There are some limitations in this study. First, the sample size is not big, especially in the experimental group; enlarging the sample size may obtain more trial results. Second, the follow-up time is short, and the long-term survival data are not enough; of course, we will continue to follow-up and dynamically update the results of the study. Also, some important data were missing, such as the duration of continuous ART treatment and dynamic HIV RNA viral quantification follow-up, which may be consistently disclosed in follow-up research articles.
Conclusion
Our single-center, comparative clinical study found that tislelizumab-based therapy had noninferior efficacy and a comparable safety profile in patients with HIV-positive versus HIV-negative advanced NSCLC. Nonetheless, the observed risk of opportunistic infections, including tuberculosis, in patients with HIV-positive calls for heightened clinical vigilance.
Acknowledgements
This research funding is provided by the Science and Technology Project of the Anti-Cancer Association of Guizhou Province (Anti-Cancer Association Science and Technology Project No. 004 [2023]).
Conflicts of interest
There are no conflicts of interest.
References
- 1.Calkins KL, Chander G, Joshu CE, Visvanathan K, Fojo AT, Lesko CR, et al. Immune status and associated mortality after cancer treatment among individuals with HIV in the antiretroviral therapy era. JAMA Oncol 2020; 6:227–235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Tanaka T, Oshima K, Kawano K, Tashiro M, Kakiuchi S, Tanaka A, et al. Nationwide longitudinal annual survey of HIV/AIDS referral hospitals in Japan From 1999 to 2021: trend in non-AIDS-defining cancers among individuals infected with HIV-1. J Acquir Immune Defic Syndr 2024; 96:1–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Konstantinidis I, Crothers K, Kunisaki KM, Drummond MB, Benfield T, Zar HJ, et al. HIV-associated lung disease. Nat Rev Dis Primers 2023; 9:39. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Bhikoo R, Allwood BW, Irusen EM, Koegelenberg CFN. Lung cancer presents at a younger age and is less likely to be curable in people living with HIV. Respiration 2024; 103:47–50. [DOI] [PubMed] [Google Scholar]
- 5.Hysell K, Yusuf R, Barakat L, Virata M, Gan G, Deng Y, et al. Decreased overall survival in HIV-associated non-small-cell lung cancer. Clin Lung Cancer 2021; 22:e498–e505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Reck M, Remon J, Hellmann MD. First-line immunotherapy for non-small-cell lung cancer. J Clin Oncol 2022; 40:586–597. [DOI] [PubMed] [Google Scholar]
- 7.Riely GJ, Wood DE, Ettinger DS, Aisner DL, Akerley W, Bauman JR, et al. Non-small cell lung cancer, version 4.2024, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2024; 22:249–274. [DOI] [PubMed] [Google Scholar]
- 8.Wang J, Qiu T, Ren S. Updates to the 2024 CSCO advanced non-small cell lung cancer guidelines. Cancer Biol Med 2025; 22:1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Bertin L, Canellas A, Abbar B, Veyri M, Spano J-P, Cadranel J, Lavolé A. Brief report of anti-programmed cell death protein-1 in human immunodeficiency virus setting: relevant and breaking results in first-line NSCLC therapy. JTO Clin Res Rep 2021; 2:100247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Assoumou L, Balde R, Katlama C, Abbar B, Delobel P, Allegre T, et al. Safety and tolerability of immune checkpoint inhibitors in people with HIV infection and cancer: insights from the national prospective real-world OncoVIHAC ANRS CO24 cohort study. J ImmunoTher Cancer 2024; 12:e009728. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Bender Ignacio R, Ddungu H, Uldrick TS. Untangling the effects of chemotherapy and HIV on CD4 counts-implications for immunotherapy in HIV and cancer. JAMA Oncol 2020; 6:235–236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Spano JP, Veyri M, Gobert A, Guihot A, Perré P, Kerjouan M, et al. Immunotherapy for cancer in people living with HIV: safety with an efficacy signal from the series in real life experience. AIDS 2019; 33:F13–F19. [DOI] [PubMed] [Google Scholar]
- 13.Ostios-garcia L, Faig J, Leonardi GC, Adeni AE, Subegdjo SJ, Lydon CA, et al. Safety and efficacy of PD-1 inhibitors among HIV-positive patients with non-small cell lung cancer. J Thorac Oncol 2018; 13:1037–1042. [DOI] [PubMed] [Google Scholar]
- 14.Shah NJ, Al-shbool G, Blackburn M, Cook M, Belouali A, Liu SV, et al. Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection. J ImmunoTher Cancer 2019; 7:353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Lavole A, Mazieres J, Schneider S, Brosseau S, Kiakouama L, Greillier L, et al. ; On behalf the French Cooperative Thoracic Intergroup (IFCT). Assessment of nivolumab in HIV-infected patients with advanced non-small cell lung cancer after prior chemotherapy. The IFCT-1602 CHIVA2 phase 2 clinical trial. Lung Cancer 2021; 158:146–150. [DOI] [PubMed] [Google Scholar]
- 16.Trickey A, Sabin CA, Burkholder G, Crane H, d’Arminio Monforte A, Egger M, et al. Life expectancy after 2015 of adults with HIV on long-term antiretroviral therapy in Europe and North America: a collaborative analysis of cohort studies. Lancet HIV 2023; 10:e295–e307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Smiley CL, Rebeiro PF, Cesar C, Belaunzaran-Zamudio PF, Crabtree-Ramirez B, Padgett D, et al. ; Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet). Estimated life expectancy gains with antiretroviral therapy among adults with HIV in Latin America and the Caribbean: a multisite retrospective cohort study. Lancet HIV 2021; 8:e266–e273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Gonzalez-Cao M, Morán T, Dalmau J, Garcia-Corbacho J, Bracht JWP, Bernabe R, et al. Assessment of the feasibility and safety of durvalumab for treatment of solid tumors in patients with HIV-1 infection: the phase 2 DURVAST study. JAMA Oncol 2020; 6:1063–1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Cook MR, Kim C. Safety and efficacy of immune checkpoint inhibitor therapy in patients with HIV infection and advanced-stage cancer: a systematic review. JAMA Oncol 2019; 5:1049–1054. [DOI] [PubMed] [Google Scholar]
- 20.Odeny TA, Lurain K, Strauss J, Fling SP, Sharon E, Wright A, et al. Effect of CD4+ T cell count on treatment-emergent adverse events among patients with and without HIV receiving immunotherapy for advanced cancer. J ImmunoTher Cancer 2022; 10:e005128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Baron M, Soulie C, Lavole A, Assoumou L, Abbar B, Fouquet B, et al. ; The Anrs Co OncoVIHAC Study Group. Impact of anti PD-1 immunotherapy on HIV reservoir and anti-viral immune responses in people living with HIV and cancer. Cells 2022; 11:1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Wang J, Lu S, Yu X, Hu Y, Zhao J, Sun M, et al. Tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: final analysis of the randomized, phase III RATIONALE-307 trial. ESMO Open 2024; 9:103727. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Lu S, Wang J, Yu Y, Yu X, Hu Y, Ai X, et al. Tislelizumab plus chemotherapy as first-line treatment for locally advanced or metastatic nonsquamous NSCLC (RATIONALE 304): a randomized phase 3 trial. J Thorac Oncol 2021; 16:1512–1522. [DOI] [PubMed] [Google Scholar]
- 24.Chang E, Sabichi AL, Kramer JR, Hartman C, Royse KE, White DL, et al. Nivolumab treatment for cancers in the HIV-infected population. J Immunother 2018; 41:379–383. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Uldrick TS, Goncalves PH, Abdul-hay M, Claeys AJ, Emu B, Ernstoff MS, et al. ; Cancer Immunotherapy Trials Network (CITN)-12 Study Team. Assessment of the safety of pembrolizumab in patients with HIV and advanced cancer-a phase 1 study. JAMA Oncol 2019; 5:1332–1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Zhuang W, Wang M, Jiang L, Su Z, Lin S. The peripheral CD4(+) T cells predict efficacy in non-small cell lung cancer (NSCLC) patients with the anti-PD-1 treatment. Transl Cancer Res 2024; 13:4052–4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Zheng QM, Li YY, Wang YP, Li G-X, Sun Z-G, Zhang M. Prognostic significance of CD4+ tumour infiltrating lymphocytes in patients with non-small cell lung cancer receiving PD-1/PD-L1 inhibitors therapy. J Coll Physicians Surg Pak 2025; 35:341–350. [DOI] [PubMed] [Google Scholar]
- 28.Gao D, Liu L, Liu J, Liu J. Predictive response and outcome of peripheral CD4(+) T cell subpopulations to combined immunotherapy and chemotherapy in advanced gastric cancer patients. Int Immunopharmacol 2024; 129:111663. [DOI] [PubMed] [Google Scholar]
- 29.Wondmeneh TG, Mekonnen AT. The incidence rate of tuberculosis and its associated factors among HIV-positive persons in Sub-Saharan Africa: a systematic review and meta-analysis. BMC Infect Dis 2023; 23:613. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Kraef C, Roen A, Podlekareva D, Bakowska E, Nemeth J, Knappik M, et al. ; the RESPOND Study Group. Incident tuberculosis in people with HIV across Europe from 2012-2022: incidence rates, risk factors, and regional differences in a multicentre cohort study. Eur Respir J 2025; 65:2401904. [DOI] [PubMed] [Google Scholar]
- 31.Kraef C, Tusch E, Singh S, Østergaard L, Fätkenheuer G, Castagna A, et al. ; EuroSIDA Study Group. All-cause and AIDS-related mortality among people with HIV across Europe from 2001 to 2020: impact of antiretroviral therapy, tuberculosis and regional differences in a multicentre cohort study. Lancet Reg Health Eur 2024; 44:100989. [DOI] [PMC free article] [PubMed] [Google Scholar]