HBV-active Antiretroviral Therapy Research Articles

Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy

In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. 67 participants (85% male, median age 49y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.

A Review on the Epidemiology of HBV and HIV Co-Infection

HIV infection has an impact on the natural course of chronic HBV infection, as it results in an increase in HBV DNA levels, accelerated progression of liver disease, and increased liver-related mortality compared with HBV mono-infection. In HIV/HBV co-infected individuals, widespread uptake and early initiation of HBV-active antiretroviral therapy have drastically improved the natural history of viral infection; however, liver disease remains common. In this paper we have reviewed the epidemiology, prevalence, treatment, pathogenesis of HIV and HBV co-infection. Co-infection of HBV-HIV is more likely to progress and complicate the disease and should be closely monitored and treated.

Persistent Hepatitis B Viraemia with Polymerase Mutations among HIV/HBV Co-Infected Patients on HBV-Active ART in KwaZulu-Natal, South Africa.

To understand the problem of persistent Hepatitis B virus (HBV) viraemia in HIV/HBV co-infected patients on HBV-active antiretroviral therapy (ART), we assessed the rate of HBV virological response in patients on HBV-active ART in KwaZulu-Natal, South Africa, and analysed factors associated with persistent HBV viraemia. One hundred and fifty eligible participants with a chronic HBV diagnosis, with or without HIV coinfection, were enrolled and followed up after 6 months. The HBV pol gene was sequenced by next-generation sequencing and mutations were determined using the Stanford HBVseq database. Logistic regression analysis was used to assess factors associated with HBV viraemia at 6-month follow-up. The mean duration of HBV-active ART was 24 months. Thirty-seven of one hundred and six (35%) participants receiving HBV-active ART for longer than 6 months had virological failure. Advanced immunosuppression with CD4+ cell counts <200 cells/μL was independently associated with persistent HBV viraemia, aOR 5.276 (95% CI 1.575–17.670) p = 0.007. A high proportion of patients on HBV-active ART are unsuppressed, which will ultimately have an impact on global elimination goals. Better monitoring should be implemented, especially in HIV-coinfected patients with low CD4+ cell counts and followed by early HBV drug-resistance testing.

Persistent chronic immune activation in HIV/HBV-coinfected patients after antiretroviral therapy.

We studied the characteristics of immune activation and investigated the underlying mechanisms in patients with human immunodeficiency virus-1/hepatitis B virus (HIV/HBV) coinfection after receiving HBV-active antiretroviral therapy. Forty patients with HIV/HBV coinfection, 38 patients with HIV monoinfection and 20 healthy controls were enrolled. CD4+ count, HIV load, HBV load, markers of immune activation and regulatory T-cell (Treg cell) frequency were assessed and compared between HIV-monoinfected and HIV/HBV-coinfected patients at week 0 (baseline), 12, 24, 36 and 48 after the onset of HBV-active antiretroviral therapy. Before antiretroviral therapy, frequencies of CD4+ HLADR+ CD38+ , CD8+ HLADR+ CD38+ , and Treg cells, and sCD163 and sCD14 levels were significantly higher in both HIV/HBV-coinfected patients and HIV-monoinfected patients, compared with healthy controls. Frequencies of CD4+ HLADR+ CD38+ and CD8+ HLADR+ CD38+ cells decreased following antiretroviral therapy in both groups. sCD163 levels did not change significantly in both groups and no significant difference was observed between the two groups at each time point during the 48-week antiretroviral therapy. In week 24, levels of sCD14 and frequencies of Treg cells appeared significantly higher in HIV/HBV-coinfected patients than in HIV-monoinfected patients, in which sCD14 levels and Treg cell frequencies declined to those in healthy controls. The Treg cell frequency was consistent with that of sCD14 levels in HIV/HBV-coinfected patients. Coinfection with HBV significantly increases sCD14 levels in HIV-infected patients during HBV-active antiretroviral therapy, which may potentially contribute to liver inflammation.

Risk of HCC With Hepatitis B Viremia Among HIV/HBV-Coinfected Persons in North America.

Chronic HBV is the predominant cause of HCC worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multicohort study of individuals coinfected with HIV/HBV. We included persons coinfected with HIV/HBV within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995-2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted HRs (aHRs [95% CIs]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, HCV), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 individuals coinfected with HIV/HBV (median age, 43 years; 93% male; 52.4% non-White), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5-2.1] events/1,000 person-years). Risk factors for HCC included age 40-49 years (aHR, 1.97 [1.22-3.17]), age ≥50 years (aHR, 2.55 [1.49-4.35]), HCV coinfection (aHR, 1.61 [1.07-2.40]), and heavy alcohol use (aHR, 1.52 [1.04-2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56-1.43]) and time-updated CD4+ percentage <14% (aHR, 1.03 [0.56-1.90]) were not. The risk of HCC was increased with time-updated HBV DNA >200IU/mL (aHR, 2.22 [1.42-3.47]) and was higher with each 1.0 log10 IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05-1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1year significantly reduced HCC risk (aHR, 0.42 [0.24-0.73]). Individuals coinfected with HIV/HBV on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.

Outcomes of acute hepatitis B virus (HBV) in HIV infection with and without HBV-active antiretroviral therapy.

Men with acute hepatitis B virus (HBV) infection in the Multicenter AIDS Cohort Study from 1985 to 2013 had serological testing to determine proportions with HBV recovery or chronic hepatitis B (CHB). A similar proportion of men without human immunodeficiency virus (HIV) and men with HIV receiving HBV-active antiretroviral therapy (ART) developed CHB [8.2%, 95% confidence interval (CI) 3.8-15.0% vs. 7.7%, 95% CI 2.00-36.0%]. In contrast, 17.5% (95% CI 8.7-29.9%) of men living with HIV, not on HBV-active ART developed CHB. HBV-active ART protects against developing CHB.

Challenges and opportunities for hepatitis B cure in the setting of HIV--hepatitis B virus co-infection.

To examine issues specific to HIV--HBV co-infection that are relevant to the search for and achieving hepatitis B cure in this the setting RECENT FINDINGS: In HIV--HBV co-infection, high rates of hepatitis B surface antigen (HBsAg) loss early after initiation of HBV-active antiretroviral therapy (ART) have previously been reported. Between 2012 and 2016, HBsAg loss from 2.8 to 23% was reported in numerous studies, including those already on suppressive HBV-active ART. Data published in 2018-2019 show that these rates have remained fairly stable (3.0-13.9%). However, it appears that higher HBsAg loss on starting HBV-active ART in co-infection falls within a few years to levels similar to that observed in long-term treated HBV mono-infection. Immune reconstitution and CD4+ T-cell recovery are likely to play a role in high HBsAg loss rates seen in early treated co-infection, although the mechanisms driving this are yet to be fully elucidated. High rates of HBsAg loss early after HBV-active ART initiation is unique to HIV--HBV co-infection, making it the ideal setting to investigate underlying mechanisms of HBV loss and develop new HBV cure strategies. This phenomenon could be used to enhance HBsAg loss with new therapeutic approaches currently being investigated; however, this is obstructed by excluding co-infection from such studies.

Long-term observation on hepatitis B surface antigen seroclearance in therapy experienced HIV/HBV co-infected Chinese.

The aim of this retrospective study was to observe hepatitis B surface antigen (HBsAg) seroclearance and explore predictors of HBsAg loss in HIV/HBV-co-infected patients receiving long-term lamivudine or both tenofovir and lamivudine containing therapies. Quantification of HBsAg, hepatitis B e antigen and HBV DNA before and after initiation of HBV-active antiretroviral therapy in a total of 268 HIV/HBV-co-infected patients started treatment between 2005 and 2017 were performed. Over a median of 65.63months of follow-up, 10 (3.7%) were observed HBsAg loss and the quantification of HBsAg in 7 (2.6%) patients were less than 50IU/mL. With the prolongation of antiretroviral therapy duration time, the rates of HBsAg seroclearance tended to increase gradually, rising from 1.8% (3/163) during 2-4years treatment to 29.4% (10/34) after antiretroviral therapy for up to 10years. Lower baseline qHBsAg and HBV DNA levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance. The event of HBsAg seroclearance is uncommon among Chinese individuals with HIV/HBV co-infection who have been treated with anti-HBV containing antiretroviral therapy, and lifelong therapy for HBV is needed for HIV/HBV co-infected patients. Baseline qHBsAg and HBV DNA levels and qHBsAg decline rate were predictors for HBsAg seroclearance.

Hepatitis B virus coinfection is associated with high early mortality in HIV-infected Tanzanians on antiretroviral therapy

There is limited data on the effect of antiviral therapies on clinical outcomes in HIV and hepatitis B virus (HBV)-infected individuals in sub-Saharan Africa. Single center, prospective longitudinal cohort study at Management and Development for Health supported HIV Care and Treatment clinics in Dar es Salaam, Tanzania. Between April 2014 and December 2015, HIV-infected, HBV-infected and HIV/HBV-coinfected, treatment naïve, Tanzanian adults more than 18 years of age were eligible for enrollment and followed for 10-18 months after initiating antivirals. All HIV-infected and HIV/HBV-coinfected participants received tenofovir, lamivudine and efavirenz; HBV-infected participants received lamivudine. Multivariate regression models were constructed to identify factors associated with mortality in HIV-infected and HIV/HBV-coinfected participants. A total of 265 HIV-infected, 165 HBV-infected and 64 HIV/HBV-coinfected participants were analyzed. At baseline, HBV-infected participants were younger and had a higher BMI than HIV-infected and HIV/HBV-coinfected participants. After a median of 371 (interquartile range 50) days on treatment, there were 40 deaths. Mortality was significantly higher among HIV/HBV-coinfected participants compared with HIV and HBV-infected participants [HIV/HBV-coinfected 12 of 64 (19%) vs. HIV-infected 26 of 265 (10%) and HBV-infected two of 265 (1%), P < 0.01]. High baseline HIV RNA and low hemoglobin levels, but not HBV coinfection were independently associated with early mortality in multivariate analyses of HIV-infected participants. High rates of early mortality were observed after treatment initiation in HIV/HBV-coinfected individuals compared with participants with HIV or HBV alone, despite robust aspartate aminotransferase to platelet ratio index declines and high rates of virologic suppression. HIV rather than HBV-related factors are more important contributors to mortality in these individuals.

HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment.

: HIV infection has a significant impact on the natural history of chronic hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated progression of liver disease and increased liver-associated mortality compared with HBV monoinfection. Widespread uptake and early initiation of HBV-active antiretroviral therapy has substantially improved the natural history of HIV-HBV coinfection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV-HBV coinfection in the era of HBV-active antiretroviral therapy and the effects of HIV directly on liver disease. We also review novel therapeutics for the management of HBV with a particular emphasis on clinical strategies being developed for an HBV cure and an HIV cure and their impact on HIV-HBV coinfected individuals.

Hepatitis B and HIV co-infection is still treated using lamivudine-only antiretroviral therapy combination in Uganda.

Hepatitis B virus (HBV) and HIV are endemic in Uganda. Co-infection is common and leads to rapid progression of liver disease. Burden of co-infection is unknown yet most patients are on lamivudine-only ART where resistance is frequent. Most patients are initiated on antiretroviral therapy (ART) without knowing their HBV status. To determine burden of co-infection and HBV viral suppression among patients on ART in Northern Uganda. We recruited HIV infected adult patients on ART in a cross-sectional study. Age, sex, ART regimen and duration were recorded. Hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBcAb) and liver panel were performed. For those HBsAg+, hepatitis B e antigen (HBeAg) and HBV DNA were performed. CD4 cell count was recorded. Three hundred patients were recruited. Twenty (6.7%) were co-infected, while 41% were anti-HBcAb+. Overall 188 (62.7%) were on lamivudine- only HBV active drug. Median ART duration 2 years (IQR 1-5), mean CD4+ cell count 317 cells/microlitre (SD 255-557). Of 20 HIV/HBV co-infected, 11/20 (55%) were on lamivudine-only ART, median duration 1.5 years. Nineteen (95%) had undetectable HBV DNA. Seventeen (85%) were HBeAg negative. Mean CD4+ cell count 327 cells/microlitre (SD 197-482). A large proportion of patients were on lamivudine- only HBV-active ART. Resistance may occur long term thus testing for HBV and correct ART is recommended.

Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

Co-infection with hepatitis B virus (HBV) and HIV is common in China; however, the impact of HBV on long-term antiretroviral therapy (ART) outcomes has not been fully characterized. Patients were classified as being HIV mono-infected (hepatitis B surface antigen (HBsAg)-negative) or HIV/HBV co-infected (HBsAg-positive). The effects of HBV on HIV virological response, changes in CD4 cell counts, hepatotoxicity, and mortality among Chinese patients receiving ART were evaluated. The HIV/HBV co-infection rate in our cohort was 9.9% (354/3562). Five hundred and fifty HIV mono-infected and 78 HIV/HBV co-infected individuals fulfilled the inclusion criteria. HIV/HBV co-infected individuals were less likely to achieve HIV-RNA suppression and a CD4 increase than HIV mono-infected individuals at 48 months post-ART. Greater hepatotoxicity and a more rapid occurrence of death were observed in HIV/HBV co-infected subjects. HBV-related mortality accounted for 84.2% (16/19) of the total deaths in HIV/HBV co-infected subjects. HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

Reply to Tsai et al

To the Editor—Tsai et al identified chronic hepatitis B virus (HBV) infection as a predictor of immunologic progression in their evaluation of chronically HBV-infected individuals with primary HIV infection who did not receive antiretroviral therapy (ART) [1]. Their findings support those from our study [2], which demonstrated the negative impact of chronic HBV infection on an AIDS or death event, thereby supporting the need for improved diagnosis, prevention and treatment of HBV infection in HIV-infected patients. They also found that lower baseline CD4 cell count was an independent predictor, which agrees with our findings of lower CD4 cell count (baseline and time-updated nadir) associated with HIV disease progression and risk of death [2]. The role of HBV-active ART in HBV/HIV coinfection management is highlighted by the importance of immune restoration in hepatitis B surface antigen clearance [3]. The movement of HIV treatment guidelines toward recommending ART for all persons with HIV infection and those with early (acute or recent) HIVinfection (BII) also underscores the importance of determining HBV status in all HIV-infected patients to optimize treatment for both viruses [4]. The findings of accelerated immunologic progression, among the other negative consequences of chronic HBV infection on HIV, warrant continued investigation into the pathogenesis of HBV effects on HIV progression and immune dysfunction.

High Seroprevalence of HBV and HCV Infection in HIV-Infected Adults in Kigali, Rwanda

BackgroundData on prevalence and incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in Rwanda are scarce.MethodsHBV status was assessed at baseline and Month 12, and anti-HCV antibodies at baseline, in a prospective cohort study of HIV-infected patients in Kigali, Rwanda: 104 men and 114 women initiating antiretroviral therapy (ART) at baseline, and 200 women not yet eligible for ART.ResultsBaseline prevalence of active HBV infection (HBsAg positive), past or occult HBV infection (anti-HBc positive and HBsAg negative) and anti-HCV was 5.2%, 42.9%, and 5.7%, respectively. The active HBV incidence rate was 4.2/1,000 person years (PY). In a multivariable logistic regression model using baseline data, participants with WHO stage 3 or 4 HIV disease were 4.19 times (95% CI 1.21–14.47) more likely to have active HBV infection, and older patients were more likely to have evidence of past exposure to HBV (aRR 1.03 per year; 95%CI 1.01–1.06). Older age was also positively associated with having anti-HCV antibodies (aOR 1.09; 95%CI 1.04–1.14) while having a higher baseline HIV viral load was negatively associated with HCV (aOR 0.60; 95% CI 0.40–0.98). The median CD4 increase during the first 12 months of ART was lower for those with active HBV infection or anti-HCV at baseline. Almost all participants (88%) with active HBV infection who were on ART were receiving lamivudine monotherapy for HBV.ConclusionHBV and HCV are common in HIV-infected patients in Rwanda. Regular HBsAg screening is needed to ensure that HIV-HBV co-infected patients receive an HBV-active ART regimen, and the prevalence of occult HBV infection should be determined. Improved access to HBV vaccination is recommended. Active HCV prevalence and incidence should be investigated further to determine whether HCV RNA PCR testing should be introduced in Rwanda.

CXCL-10, Interleukin-12 and Interleukin-21 are not Immunological Predictors of Hbeag Seroconversion in HIV-1–HBV Coinfection following HBV-Active Antiretroviral Therapy

Interferon stimulated chemokine CXCL-10, interleukin (IL)-12 (p70) and IL-21 have been associated with HBsAg and HBeAg loss following treatment of HBV monoinfection. The aim of this study was to determine whether these factors were also associated with HBsAg and HBeAg loss in HIV-HBV-coinfected patients following HBV-active combination antiretroviral therapy (cART). HIV-HBV-coinfected patients with HBeAg seroconversion (n=12; seroconverters [SC]) were compared to patients who did not seroconvert (n=13; non-seroconverters [NSC]). CXCL-10, IL-12 and IL-21 (Luminex Bead Array, Life Technologies, Grand Island, NY, USA) were measured in plasma prior to initiation of HBV-active cART (baseline), at the time of seroconversion (T0) and at the closest time point before (T-1) and after (T+1) seroconversion. Levels of CXCL-10 declined significantly in all patients following HBV-active cART (P<0.05 for both SC and NSC; Kruskall-Wallis, Dunn's post-test). There was no difference between SC and NSC in the level of CXCL-10, IL-12 and IL-21 at any time point. We found no evidence that CXCL-10, IL-12 or IL-21 were associated with HBeAg seroconversion following HBV-active cART. Other immunological determinants should be explored in this setting.

Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand

BackgroundHepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited.MethodsThe Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naïve HIV-HBV individuals in Thailand.ResultsEarly HF (EHF) was defined as ALT > 5 × ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053).ConclusionEHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process.Clinical Trial numberNCT00192595.

An HIV Patient with Hepatic Flare after the Initiation of HBV-active Antiretroviral Therapy

A 39-year-old man presented a CD4 T cell count of 78/µL and HIV-RNA at 6.6 × 10(5) copies/mL at his first medical examination. After the 58th day, we initiated HBV-active antiretroviral therapy. Three months after the start of antiretroviral therapy, he was diagnosed with hepatic flare on the basis of elevated AST and ALT levels without detecting HBV-DNA. Although after continuing the medication his AST and ALT levels increased to 700 IU/L and 1,400 IU/L, respectively, he showed improvement following a natural course and was discharged from hospital after the 169th day. This is a case of hepatic flare likely caused by immune reconstitution associated with resolved HBV infection.

Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression

to determine if intrahepatic immune activation is increased in HIV-hepatitis B virus (HBV) co-infected patients compared to HBV mono-infected patients and whether this reduced following HBV-active antiretroviral therapy (ART) in HIV-HBV co-infected patients. : Case-control observational study. we examined liver biopsies for markers of T-cell and monocyte infiltration and activation, natural killer cells, hepatic stellate cell (HSC) activation (staining for alpha smooth muscle actin) and apoptosis [using terminal dUTP nick-end labelling (TUNEL)] in treatment-naive Asian HIV-HBV co-infected (n = 16) and HBV mono-infected patients matched for age and HBV e-antigen status (n = 16). Liver biopsies from a subset of co-infected patients (n = 15) were also compared prior to and following 48 weeks of HBV-active ART. HIV-HBV co-infected patients had a median CD4 T-cell count of 25 cells/microl and lower alanine aminotransferase levels than HBV mono-infected patients (P = 0.03). In HIV-HBV co-infected patients, hepatocyte apoptosis was increased (P = 0.04) but there were fewer intrahepatic CD4 and CD8 T cells (P < 0.001), lower activation of intrahepatic T cells, Kupffer cells and HSC (P = 0.002, 0.008 and < 0.001, respectively). Following ART, there was a significant decrease in intrahepatic HBsAg staining (P = 0.04) and Kupffer cell activation (P = 0.003). we found no evidence of increased intrahepatic mononuclear and HSC activation in this cohort of HIV-HBV co-infected individuals with advanced immune suppression. An increase in intra-hepatic apoptosis in HIV-HBV co-infected individuals may potentially contribute to accelerated fibrosis in this setting.

Longer Duration of HBV-Active Antiretroviral Therapy is Linked to Favorable Virological Outcome in HIV-HBV Co-infected Patients

Background: HBV-HIV co-infection is associated with increased liver-related morbidity and mortality. Herein we analyzed HBV-related virologic and clinical outcomes in HBV-HIV patients in the HAART era. Methods: HBsAg positive HIV-infected patients followed at a US academic center between 1990 and 2008 were assessed in a retrospective and longitudinal study. Factors associated with HBsAg and/or HBeAg clearance and with advanced liver disease were evaluated using logistic regression. Results: 72 patients were evaluated. Their median time of follow-up and of adherence to HBV-active HAART were 3 and 1 years, respectively. HBeAg and HBsAg cleared in 17.6% and 5.5% of patients, respectively. More prolonged use of HBV-active HAART predicted clearance of HBeAg (odds ratio [OR] 2.66, 95% CI 1.15–6.16, p = .02) and of HBsAg (OR 1.54, 95% CI 1.02–2.31, p = .04). Patients clearing HBsAg tended to have higher baseline CD4 (mean CD4 counts: 550 vs. 246 cells/mm3; p = .06). Rate of diagnosis of liver-related complications and death were 24.6/1,000 and 10.5/1,000 patient-years, respectively. Higher ALT levels before HAART initiation were associated with the diagnosis of cirrhosis during follow-up (OR 1.02, 95% CI 1.002–1.03, p = .02). Conclusions: Prolonged use of HBV-active HAART favors HBsAg and HBeAg clearance in HIV-HBV co-infected patients. Those with higher ALT levels at presentation have higher risk of being diagnosed with cirrhosis during the first few years of follow-up.