Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate.
ABSTRACT The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients.
We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models.
The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P < 0.05). HBV-DNA decay was biphasic, with an rapid fall followed by a gradual decline. Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations. Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA < 10 log, 316 days when HBV-DNA > 10 log) and positive HBeAg. Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations.
The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.
SourceAvailable from: Eleanor BarnesHIV Medicine 11/2013; 14 Suppl 4:1-71. DOI:10.1111/hiv.12106 · 3.45 Impact Factor
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ABSTRACT: Despite widespread use in HIV and hepatitis B virus (HBV) infection, the effectiveness of tenofovir (TDF) has not been studied extensively outside of small HBV-HIV coinfected cohorts. We examined the effect of prior lamivudine treatment (3TC) and other factors on HBV DNA suppression with TDF in a multi-site clinical cohort of coinfected patients. We studied all patients enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort from 1996-2011 who had chronic HBV and HIV infection, initiated a TDF-based regimen continued for ≥3 months and had on-treatment HBV measurements. We used Kaplan-Meier curves and Cox-Proportional hazards to estimate time to suppression (HBV DNA level <200 IU/ml or <1000 copies/ml) by selected covariates. Among 397 coinfected patients on TDF, 91% were also on emtricitabine or 3TC concurrently, 92% of those tested were HBeAg-positive, 196 (49%) had prior 3TC exposure; 192 (48%) achieved HBV DNA suppression over a median of 28 months (IQR 13-71). Median time to HBV DNA suppression was 17 months for those who were 3TC-naïve and 50 months for those who were 3TC-exposed. After controlling for other factors, prior 3TC exposure, baseline HBV DNA level >10,000 IU/ml, and lower nadir CD4 count were independently associated with decreased likelihood of HBV DNA suppression on TDF. These results emphasize the role of prior 3TC exposure and immune response on delayed HBV suppression on TDF.JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2014; DOI:10.1097/QAI.0000000000000126 · 4.39 Impact Factor
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ABSTRACT: Background. Although tenofovir (TDF) use has increased as part of first-line antiretroviral therapy (ART) across sub-Saharan Africa, renal outcomes among patients receiving TDF remain poorly understood. We assessed changes in renal function and mortality in patients starting TDF- or non-TDF-containing ART in Lusaka, Zambia. Methods. We included patients aged ≥16 years who started ART from 2007 onward, with documented baseline weight and serum creatinine. Renal dysfunction was categorized as mild (eGFR 60-89 mL/min), moderate (30-59 mL/min) or severe (<30 mL/min) using the CKD-EPI formula. Differences in eGFR during ART were analyzed using linear mixed-effect models, the odds of developing moderate or severe eGFR decrease with logistic regression and mortality with competing risk regression. Results. We included 62,230 adults, of which 38,716 (62%) initiated a TDF-based regimen. The proportion with moderate or severe renal dysfunction at baseline was lower in the TDF compared to the non-TDF group (1.9% vs. 4.0%). Among patients with no or mild renal dysfunction, those on TDF were more likely to develop moderate (adjusted OR: 3.11; 95%CI: 2.52-3.87) or severe eGFR decrease (adjusted OR: 2.43; 95%CI: 1.80-3.28), although the incidence of such episodes was low. Among patients with moderate or severe renal dysfunction at baseline, renal function improved independently of ART regimen and mortality was similar in both treatment groups. Conclusions. TDF use did not attenuate renal function recovery or increase mortality in patients with renal dysfunction. Further studies are needed to determine the role of routine renal function monitoring before and during ART use in Africa.Clinical Infectious Diseases 02/2014; 58(10). DOI:10.1093/cid/ciu117 · 9.42 Impact Factor