Early Emergence of Opportunistic Infections After Starting Direct-acting Antiviral Drugs in HIV/HCV-coinfected Patients

Juan Macías; Francisco Téllez; Antonio Rivero-Juárez; Rosario Palacios; Luis E. Morano; Dolores Merino; Antonio Collado; Lucio García-Fraile; Mohamed Omar; Juan A. Pineda; On behalf of the HEPAVIR, GEHEP and RIS-HEP07 study groups


J Viral Hepat. 2019;26(1):48-54. 

In This Article


Characteristics of the Study Population

Overall, 848 patients with HIV and HCV coinfection were included in the cohort by nine units that accepted to review their clinical records for the present study. From them, 735 (87%) patients had an evaluable response at the scheduled date of SVR12 assessment, and treatment was ongoing or SVR12 pending evaluation in 113 (13%) individuals. By intention-to-treat (ITT) approach, considering all patients without documented SVR12 as treatment failures, 673 (92%) out of 735 with evaluable response achieved SVR12. The baseline characteristics of the cohort are outlined in Table 1.

Incidence of Infections

During the period of observation, 38 (4.5%) patients suffered from infections. The baseline characteristics of these patients were not significantly different from those who did not develop infections, but for nadir CD4 cell counts and the proportion of subjects with previous AIDS diagnosis (Table 1). The global incidence of infections was 4.6 (3.3–6.3) per 100 person-years and the time since DAA initiation until the onset of infections was 23 (7.3–33) weeks. The frequency of immunodepression-related infections was 9 (1.1%), and the incidence of those was 0.99 (0.42–1.85) per 100 person-years. The median (Q1-Q3) time since DAA initiation until the onset of infections was 17 (11–34) weeks.

A group of 2228 HIV-infected patients were identified as control group, and 1759 (79%) of them were men. Regarding the risk factors for HIV transmission, 1123 (50%) patients reported injecting drug use, and 1053 (47%) patients had sexual risk factors. AIDS-defining events were observed in 614 (28%) patients previously, before the period of observation. The median (Q1-Q3) CD4 cell counts were 604 (375–861) cells/μL and 2139 (96%) patients showed undetectable HIV load at their first visit during the period of observation. HCV coinfection with detectable plasma HCV RNA was present in 234 (11%) patients who were not treated with DAAs during the study period. Overall, 14 (0.6%) patients presented infections during the period of observation. Of those, four (0.2%) infections were related to immunosuppression: two multimetameric herpes zoster, one oral herpes simplex and one oral candidiasis. The global incidence of infections was 0.4 (0.2–0.8) per 100 person-years for the control group compared with 4.6 (3.3–6.3) per 100 person-years for patients treated with DAA (P < 0.001). The incidence of immunodepression-related infections was 0.1 (0.04–0.4) per 100 person-years for the control group compared with 0.99 (0.42–1.85) per 100 person-years for patients treated with DAA (P < 0.001).

Description of Infections

Five (13%) patients with infections died during the study period; four of them had cirrhosis. In four individuals, there was an early onset of infection, before finishing anti-HCV treatment.

Nine individuals showed immunodepression-related infections (Table 2). All of them maintained suppressed plasma HIV RNA with ART at the time of the infection. Three patients with immunodepression-related infection had cirrhosis. Two patients presented AIDS-defining infections. One of them, with high CD4 cell counts and undetectable plasma HIV RNA (Table 2), presented with clumsiness, progressive weakness and speech changes. He was diagnosed with progressive multifocal leukoencephalopathy (PML) on the basis of compatible imaging findings and identification of JC virus DNA in cerebrospinal fluid. He achieved SVR12 and suffered from persistent residual neurologic deficits with HIV viral load suppressed with ART. Another patient was admitted because of meningitis after 6 weeks of starting a DAA combination. The patient was on ART since three years before. The opening pressure of the cerebrospinal fluid was high, and cerebrospinal fluid examination showed mononuclear cell pleocytosis. Cryptococcus neoformans was detected in cerebrospinal fluid cultures. He received antifungal therapy and fully recovered of the cryptococcal meningitis. Multimetameric herpes zoster was the most common event, appearing in four patients. One patient had fever and a typical chickenpox rash. HIV replication was suppressed by ART, but CD4 cell counts were below 200 cells/μL at the date of presentation. He died of rapidly evolving respiratory failure after 36 hours of the initial symptoms. The diagnosis of disseminated varicella-zoster virus (VZV) was confirmed by a Tzanck smear showing multinucleated cells and the detection of VZV DNA in vesicular fluid.