On 8 May 2021, a 53-year-old man was admitted to the hospital for treatment at the Fourth People's Hospital of Nanning (Nanning, Guangxi, China) for Acquired Immunodeficiency Syndrome (AIDS), Marneffei talaromycosis and fungal esophagitis. The patient's baseline HIV RNA was 559,000 copies/mL and the CD4 count was 12 cells/microL. Due to resource constraints, baseline resistance genotype testing was not performed. The patient self-reported that he had a history of prostitution more than 10 years ago, but had not had sex in the past five years, and denied a history of drug use and ART. In April 2021, he was suspected of having tuberculosis (TB) at the First Affiliated Hospital of Guangxi Medical University, but he had not been further diagnosed or received anti-TB treatment. During the hospitalization in our hospital, the chest imaging of the patient indicated that TB could not be excluded (atypical TB foci), but the sputum smear and culture were negative, and the sputum TB-DNA was also negative. Besides, after anti-fungal and bacterial treatment, the patient's condition improved and the lung foci shrank, so it was still difficult to identify TB. For ART regimens, existing antiviral drugs in China include NRTIs (Tenofovir disoproxil (TDF), Zidovudine (AZT), 3TC), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (Efavirenz (EFV), Nevirapine (NVP)), protease inhibitors (PIs) (Lopinavir/Ritonavir (LPV/r)), INSTIs (DTG, Raltegravir (RAL), BIC/FTC/TAF, DTG/3TC, Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF)) and fusion inhibitors (FIs) (Albuvirtide (ABT)). Considering that the patient had a variety of opportunistic infections, TB could not be ruled out, the hemoglobin was 69g/L, and the clearance rate of endogenous creatinine was 41.93 mL/min, using TDF or AZT was not appropriate. If TB was later diagnosed, rifampicin was required, and rifampicin was contraindicated in combination with EVG/NVP/LPV/r/BIC. The patient's current anti-fungal drugs (itraconazole) interact with EFV, NVP, and LPV/r. ABT is generally only used for special patients with drug resistance and inability to eat due to its high price. The only remaining treatment regimen, DTG/3TC, was shown to have high rates of viral suppression in HIV-naive patients with HIV RNA>500,000 copies/mL in multiple multicenter real-world studies. It was also taken into account that despite the lack of baseline resistance data, no patients with treatment failure due to pretreatment integrase resistance were identified in Nanning. Therefore, DTG/3TC was selected as the initial treatment regimen for this patient.
The patient was discharged after treatment improved on 1 June 2021. After being discharged, he reported taking DTG/3TC regularly. However, at the end of July, he began to suffer from general fatigue and anorexia. When he returned to the hospital on 26 August for a follow-up visit, his CD4 count was 3 cells/microL. Considering that the patient had only received ART for 3 months, it was not a treatment failure, and the poor immune status might be due to a previous serious opportunistic infection that had not recovered CD4. However, considering the patient's high baseline HIV RNA and low CD4, on 27 August, we adjusted the treatment regimen to BIC/FTC/TAF, which is less restrictive than DTG/3TC in the guidelines.
From 28 August to 19 September 2021, he was re-hospitalized due to general fatigue and anorexia, and was diagnosed as "1. Marneffei talaromycosis 2. AIDS 3. Bacterial pneumonia 4. Bone marrow suppression after infection (granulocytopenia, severe anaemia) 5. Secondary pulmonary TB upper-middle-lower/upper-middle-bottom smear (-) and culture (-) initial treatment." On 17 September 2021, we found that the patient's HIV RNA was 163,200 copies/mL, which was most likely caused by the failure of anti-HIV treatment or non-adherence or uncontrolled opportunistic infections. Therefore, he was switched to BIC/FTC/TAF + LPV/r. At the same time, after anti-fungal, anti-bacterial, anti-TB (isoniazid, ethambutol, pyrazinamide, and levofloxacin) and other symptomatic treatment, he was improved and was discharged.
From 25 September to 11 October 2021, he was hospitalized for a third time due to general fatigue and anorexia, with the same diagnosis as before. On 29 September, we sent the patient's blood samples to Guangzhou Hailite Biotechnology Co., Ltd., China for HIV resistance genotype testing (Sanger sequencing. The testing fee was funded by the scientific research funds). The results showed that the virus type was CRF01-AE, and the NRTIs-related sites D67N, K70R, M184V, T125V, and K219Q were mutated, suggesting that the virus strain was resistant to abacavir (ABC), AZT, stavudine (d4T), didanosine (ddI), FTC, 3TC, and TDF. The INSTIs-related sites E138K, G140A, S147SG, and Q148R were also mutated, indicating that the virus strain was resistant to BIC, cabotegravir (CAB), DTG, EVG, and RAL. However, there was no drug resistance to PIs and NNRTIs (Table 1). According to the resistance test results, the ART regimen was adjusted to 3TC + EFV + LPV/r. For the choice of NRTIs, among the three drugs (TDF, AZT, 3TC) available in China, TDF and AZT were not appropriate considering that the patient's endogenous creatinine clearance rate was 14.94 mL/min and hemoglobin was 44g/L. Although the patient had M184V mutation, 3TC might still have certain antiviral ability. After comprehensive consideration, we chose 3TC. 
The patient was admitted to the hospital for a fourth time on 4 November 2021, due to general fatigue and anorexia. During the hospitalization, his CD4 count was 5 cells/microL and HIV RNA was 82.2 copies/mL; the drug resistance test could not be performed due to the low HIV RNA. The patient died on 15 November 2021, due to an aggravated opportunistic infection. The final diagnoses were Sepsis, Septic shock, Bone marrow suppression after infection, Marneffei talaromycosis, TB, and AIDS. Throughout treatment, the patient stated that he had taken antiviral drugs regularly, which was also confirmed by his family. The diagnosis and treatment process related to this patient was shown in Figure 1.