Lung cancer is the most common non-AIDS defining malignancy (non-ADM) and the leading source of non-ADM mortality in persons living with HIV/AIDS (PLWHA)1. Lung cancer incidence in HIV patients is 0.79 [0.66-0.92]/1000 PY2. It appears that the incidence of non-small cell lung cancer (NSCLC) is increased in people living with HIV infection but there is no evidence of an increased incidence of small cell lung cancer (SCLC) for some authors3, 4. Nevertheless other authors consider that the risk of lung cancer in the setting of HIV infection is elevated for all major lung cancer subtypes (adenocarcinoma, squamous cell carcinoma and small cell carcinoma) and has not been significantly modified by the introduction of HAART5. Engels et al6 reported that the relative risk (RR) of lung cancer occurring during the pre-HAART era [2.5 (95% CI 1.9-3.3)] was similar to that described in the early [3.3 (95% CI 2.9-3.8)] and recent HAART era [2.6 (95% CI 2.1-3.1)].
Cumulative mortality estimates were particularly high in the 140 individuals
diagnosed with lung cancer in the D:A:D Study (57.2% [48.4-65.9] and 77.0% [67.3-86.8] at 1 and 2.5 years, respectively. HCV co-infection and disseminated cancer at time of diagnosis were predictors of mortality among patients with lung cancer. No association was seen in univariate analyses between the latest CD4 count and mortality from lung cancer (relative hazard per 50 cells/mm3 higher: 0.99 [95% confidence interval 0.95-1.03], p = 0.70)2. Nevertheless, in a French cohort with more than 52.000 HIV-positive individuals7, a RR of 2.2 (95% CI 1.3-3.6) for lung cancer has been reported in patients with current CD4 cell count between 350 and 500 cells/µl and 8.5 (95% CI 4.3-16.7) in patients with current CD4 counts <50 cells/µl, when compared to HIV-positive patients with current CD4 cell count >500 cells/µl.
Considering that smoking is the major etiologic agent of lung cancer, heavier smoking exposure has been considered as the main explanation for higher rates of lung cancer observed in the setting of HIV. In fact, among HIV-infected individuals smoking rates range from 35% to 70%, compared to approximately 20% in the general US population. However, HIV infection has been associated with increased lung cancer incidence even after controlling for smoking history data. The incidence rate ratio (IRR) of lung cancer associated with HIV infection remains significant even after multivariable adjustment for major confounders, including smoking and age (IRR 1.7; 95% CI 1.5-1.9)5.
The most recent studies demonstrated similar survival rates among HIV-positive lung cancer patients as compared with HIV-negative8.
Patients with HIV-related NSCLC present at a younger age and with more advanced disease than their HIV-negative counterparts. The rise in incidence of adenocarcinoma in the HIV-negative population has also been seen in people living with HIV/AIDS9.
More than 80% of lung cancer patients refer symptoms for less than 3 months. Most frequent symptoms are: cough (75%), asthenia (50%), weight loss (57%), chest pain (50%), haemoptysis (20-50%), dyspnoea (40%), dysphonia (15%), bone pain (9%), dysphagia (3%).
NSCLC : CT chest and upper abdomen, including adrenals; pulmonary function tests (PFTs); consider PET/CT scan; patients with a strong clinical suspicion of stage I or II lung cancer (risk factors and radiologic appearance) do not require a biopsy before surgery. Bronchoscopy should preferably be performed during the planned surgical resection. Invasive mediastinal staging is recommended before surgical resection for most patients with clinical stage I or II lung cancer. Brain MRI is also recommended. Smoking cessation counseling and intervention are recommended.
For T, N, M definitions, Anatomic Stages and Prognostic Groups see NCCN Guidelines for NSCLC, version 2.2014, pages 59-61.
SCLC11: chest/liver/adrenal CT with intravenous contrast whenever possible; brain MRI (preferred) or CT scan with intravenous contrast whenever possible; PET/CT scan if limited stage is suspected; smoking cessation counseling and intervention. If pleural effusion is present consider thoracentesis; if thoracentesis is inconclusive, consider thoracoscopy.
For T, N, M definitions, Anatomic Stages and Prognostic Groups see NCCN Guidelines for SCLC, version 2.2014, pages 20-21.
As a significant increase in myelosuppression has been reported for patients also taking protease inhibitors, it may be worth interrupting HAART prior to chemotherapy if the patient’s HIV is well controlled9.
SCLC: cisplatin and etoposide for all stages. Associated concomitant chest RT for limited disease is recommended. All patients who achieve complete remission should undergo whole-brain RT.
The evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer. Clinicians with access to high-volume, high-quality lung cancer screening and treatment centers may initiate a discussion about screening with apparently healthy PLWHA aged 55–74 years who have at least a 30 pack-year smoking history and who currently smoke or have quit smoking within the past 15 years12.
The importance of stopping smoking is a crucial message during clinical encounters. A recent cohort study13 from Denmark, where HIV care is well organized and antiretroviral therapy is free, showed that HIV-infected smokers lose more life-years to smoking than to HIV (12.3 vs. 5.1 years). Lung cancer screening must not be viewed as an alternative to smoking cessation12.
Cisplatin and dolutegravir: in vitro data indicate that dolutegravir is a moderate inhibitor of cisplatin renal elimination so it is recommended to monitoring for cisplatin related side effects.
Cisplatin and cobicistat: in vitro data indicate that cobicistat is a moderate inhibitor of cisplatin renal elimination so it is recommended to monitoring for cisplatin related side effects.
Cisplatin and tenofovir: coadministration may increase the risk of nephrotoxicity (closely monitor renal function).
Cisplatin and fenitoin: cisplatin decreases fenitoin plasma concentrations.
Efavirenz or Etravirine and erlotinib: EFV or ETV could potentially decrease erlotinib concentrations.
Any PI (with or without ritonavir) and erlotinib: coadministration of a potent CYP3A4 inhibitor like any PI and erlotinib should be avoided.
Any PI or EVG/COBI may increase etoposide exposure.
NNRTI except rilpivirine could potentially decrease etoposide exposure.
An urgent referral for a chest X-ray should be made when a patient presents with: haemoptysis, or any of the following unexplained persistent (that is, lasting more than 3 weeks) symptoms and signs: chest and/or shoulder pain, dyspnoea, weight loss, hoarseness, finger clubbing, cervical and/or supraclavicular lymphadenopathy, cough with or without any of the above features suggestive of metastasis from a lung cancer (for example, in brain, bone, liver or skin). A report should be made back to the referring primary healthcare professional within 5 days of referral.
An urgent referral should be made for either of the following: persistent haemoptysis in smokers or ex-smokers who are aged 40 years and older or a chest X-ray suggestive of lung cancer (including pleural effusion and slowly resolving consolidation). Immediate referral should be considered for the following: signs of superior vena caval obstruction (swelling of the face and/or neck with fixed elevation of jugular venous pressure) or stridor.