Poor CD4/CD8 ratio recovery in HBcAb-positive HIV patients with worse immune status is associated with significantly higher CD8 cell numbers.

Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8 < 0.45 in the HIV/HBV coinfected group. A significant increase in the CD8 T cell count was shown up to 24 months after the initiation of effective cART in the subgroup of patients with the worst immune status.

Hepatitis B virus reactivation sustained by a hepatitis B virus surface antigen immune-escape mutant isolate in a patient who was hepatitis B core antibody positive during treatment with sofosbuvir and velpatasvir for hepatitis C virus infection: a case report.

BACKGROUND: Although several cases of hepatitis B virus reactivation have been described in patients with a history of hepatitis B virus infection while undergoing treatment for hepatitis C virus infection with direct acting antivirals, the question of whether hepatitis B virus surface antigen immune-escape mutations might play a role has not been addressed so far. CASE PRESENTATION: We report a case of hepatitis B virus reactivation in a Caucasian patient infected with hepatitis C virus during treatment with sofosbuvir and velpatasvir. A 50-year-old man with a genotype 1a hepatitis C virus infection was considered for therapy. His serological profile was hepatitis B virus surface antigen-negative, hepatitis B virus core antibody-positive, hepatitis B virus surface antibody-negative, and anti-hepatitis D virus-positive. The detection of hepatitis B virus deoxyribonucleic acid (DNA) indicated active viral replication during the direct acting antiviral treatment that spontaneously returned to undetectable levels after treatment completion. Starting from week 12 after the end of treatment, hepatitis B virus surface antibody titers and hepatitis B virus e antibody developed. Sequencing analysis revealed the hepatitis B virus genotype D3 and the presence of two relevant immune-escape mutations (P120S and T126I) in the major hydrophilic region by analyzing the S region. CONCLUSIONS: We speculate that the presence of the hepatitis B virus surface antigen mutations, endowed with the enhanced capability to elude the immune response, could play a role in hepatitis B virus reactivation. This observation confirms that occult hepatitis B infection should also be carefully monitored, through surveillance of the hepatitis B virus viral load before and during direct acting antiviral treatment of hepatitis C virus.

HBcAb seropositivity is correlated with poor HIV viremia control in an Italian cohort of HIV/HBV-coinfected patients on first-line therapy.

The morbidity and mortality rates of human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection are higher than that of either infection alone. Outcomes and the virological response to antiretrovirals (combination antiretroviral therapy, cART) were explored in HIV/HBV subjects in a cohort of Italian patients treated with cART. A single-center retrospective analysis of patients enrolled from January 2007 to June 2018 was conducted by grouping patients by HBV status and recording baseline viro-immunological features, the history of virological failure, the efficacy of cART in achieving HIV viral undetectability, viral blip detection and viral rebound on follow up. Among 231 enrolled patients, 10 (4.3%) were HBV surface (s) antigen (HBsAg)-positive, 85 (36.8%) were positive for antibodies to HBV c antigen (HBcAb) and with or without antibodies to HBV s antigen (HBsAb), and 136 were (58.9%) HBV-negative. At baseline, HBcAb/HBsAb+/--positive patients had lower CD4+ cell counts and CD4+ nadirs (188 cell/mmc, IQR 78-334, p = 0.02 and 176 cell/mmc, IQR 52-284, p = 0,001, respectively). There were significantly higher numbers of AIDS and non-AIDS events in the HBcAb+/HBsAb+/--positive subjects than in the HBV-negative patients (41.1% vs 19.1%, p = 0.002 and 56.5% vs 28.7%, respectively, p ≤ 0.0001); additionally, HIV viremia undetectability was achieved a significantly longer time after cART was begun in the former than in the latter population (6 vs 4 months, p = 0.0001). Cox multivariable analysis confirmed that after starting cART, an HBcAb+/HBsAb+/--positive status is a risk factor for a lower odds of achieving virological success and a higher risk of experiencing virological rebound (AHR 0.63, CI 95% 0.46-0.87, p = 0.004 and AHR 2.52, CI 95% 1.09-5.80, p = 0.030). HBcAb-positive status resulted in a delay in achieving HIV < 50 copies/mL and the appearance of viral rebound in course of cART, hence it is related to a poor control of HIV infection in a population of coinfected patients.