Meta-Analysis of the Risk for Abnormal Liver Function in Pregnancy with High HBV DNA After Antiviral Therapy Withdrawal.

Objective: We aimed to explore the relationship between the withdrawal of antiviral therapy after delivery and the risk for abnormal liver function (ALF) after delivery in pregnant women with high hepatitis B virus (HBV) DNA load by meta-analysis, in order to provide the corresponding theoretical basis for further guiding the clinical use of antiviral drugs in such pregnant women. Methods: We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy from January 1, 2010 to November 1, 2020. Study selection and data extraction were performed by pairs of independent reviewers. The main index was the percentage of ALF higher than the upper limit of normal at 0 to 12 and 12 to 24 weeks after delivery. Meta-analysis was used to compare the risk for ALF after stopping antiviral drugs at different time points following delivery, and subgroup analysis was conducted according to the types of drugs used. Results: We included 10 studies that enrolled 1080 pregnant women. There were 749 pregnant women in the treatment group and 331 pregnant women in the control group (who were not treated with antiviral therapy). The risk ratio (RR) for ALF in the 2 groups at 0 to 12 weeks after delivery: RR = 0.88; 95% CI, 0.71-1.09; at 12-24 weeks: RR = 0.46; 95% CI, 0.29-0.73, were compared. According to the different types of medication, subgroup analysis showed that the lamivudine treatment group compared with the control group at 0-12 weeks: RR = 0.67; 95% CI, 0.26-1.75; at 12-24 weeks, RR = 0.27; 95% CI, 0.11-0.67. The telbivudine treatment group was compared with the control group: at 0-12 weeks: RR = 0.77; 95% CI, 0.43-1.39; at 12-24 weeks: RR = 0.62, 95% CI, 0.23-1.64. The tenofovir treatment group was compared with the control group: at 0-12 weeks RR = 1.02; 95% CI, 0.67-1.55; at 12-24 weeks RR = 0.5; 95% CI, 0.25, 0.99. The lamivudine antiviral treatment group was further analyzed according to different treatment withdrawal time points. Compared with the control group, the immediate withdrawal of lamivudine in labor group at 0-12 weeks RR = 0.29; 95% CI, 0.11-0.77; at 12-24 weeks RR = 0.22; 95% CI, 0.05-0.88; the results were significantly different. There was no significant difference between the 4-week group and the 4-12 week group and the control group. Conclusion: In pregnant women with a high HBV DNA load, immediate withdrawal after antiviral treatment in the second or third trimester of pregnancy did not increase the risk for ALF after delivery.

Dual therapy with lopinavir/ritonavir plus lamivudine could be a viable alternative for antiretroviral-therapy-naive adults with HIV-1 infection regardless of HIV viral load or subgenotype in resource-limited settings: A randomised, open-label and non-inferiority study from China.

BACKGROUNDS: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-naïve HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). METHODS: 198 were randomised to DT (n = 100) or TT (n = 98). RESULTS: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. CONCLUSION: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.

Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study.

OBJECTIVES: Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. PATIENTS AND METHODS: We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). RESULTS: During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. CONCLUSIONS: In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.

The genetic toxicity effects of lamivudine and stavudine antiretroviral agents.

IMPORTANCE OF THE FIELD: The nucleoside reverse transcriptase inhibitors (NRTIs) are used in antiretroviral therapy worldwide for the treatment of HIV infections. These drugs act by blocking reverse transcriptase enzyme activity, causing pro-viral DNA chain termination. As a consequence, NRTIs could cause genomic instability and loss of heterozygosity. AREAS COVERED IN THIS REVIEW: This review highlights the toxic and genotoxic effects of NRTIs, particularly lamivudine (3TC) and stavudine (d4T) analogues. In addition, a battery of short-term in vitro and in vivo systems are described to explain the potential genotoxic effects of these NRTIs as a single drug or a complexity of highly active antiretroviral therapy. WHAT THE READER WILL GAIN: The readers will gain an understanding of a secondary effect that could be induced by 3TC and d4T treatments. TAKE HOME MESSAGE: Considering that AIDS has become a chronic disease, more comprehensive toxic genetic studies are needed, with particular attention to the genetic alterations induced by NRTIs. These alterations play a primary role in carcinogenesis and are also involved in secondary and subsequent steps of carcinogenesis.

Effect of Chinese medicine therapy for strengthening-Pi and nourishing-Shen in preventing lamivudine induced YMDD mutation and its immunologic mechanism.

OBJECTIVE: To observe the effect of Chinese medicine therapy for strengthening-Pi and nourishing-Shen (SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism. METHODS: One hundred and sixty chronic hepatitis B (CHB) patients with positive HBeAg were equally assigned to two groups at random: the observation group and the control group. Patients in the observation group were treated with lamivudine combined with SPNS, and those in the control group were treated with lamivudine only, with the treatment lasting for 52 weeks in total. Changes in indexes, including liver function, HbeAg, HBV-DNA, YMDD variation, CD(4), CD(4)/CD(8) ratio, interferon-gamma (IFN-gamma), interleukin-4 (IL-4), blood routine, renal function, as well as any adverse reactions that occurred in patients, were observed at different time points. RESULTS: The ALT, AST recovery rate and HBV-DNA negatively inversing rate at the 24th week, the 36th week and the 52nd week were all higher (P<0.05); meanwhile, the YMDD mutation rate at the 36th week and the 52nd week was lower (P<0.05) in the observation group than in the control group. The posttreatment levels of CD(4), CD(4)/CD(8) ratio, IFN-gamma, and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group (P<0.05). CONCLUSION: Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV, and the mechanism may be related to its regulation of the CD(4) level, CD(4)/CD(8) ratio and Th1/Th2 balance.

Results of up to 2 years of entecavir vs lamivudine therapy in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B.

Entecavir is a potent inhibitor of hepatitis B virus (HBV) polymerase. The efficacy and safety of entecavir in nucleoside-naïve patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B was established in a large, international, double-dummy study (ETV-022) where patients were randomized to entecavir 0.5 mg/day (n = 354) or lamivudine 100 mg/day (n = 355) once daily. ETV-022 had a 52-week blinded treatment phase, followed by an extended blinded treatment phase for up to 44 additional weeks (96 weeks total). Treatment was discontinued for patients achieving a protocol-defined response as determined by patient management criteria that intended to test the possibility of finite therapy, which has not previously been studied for entecavir or other anti-HBV agents in a large trial. Early results from this study have been previously presented/published separately. This paper compiles the results of up to 2 years of treatment for protocol-defined responders, virologic responders and nonresponders. For responders who discontinued therapy (per protocol), 24-week off-treatment evaluation is presented to provide a more 'complete picture' of what clinicians can expect when treating nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. For patients who discontinued therapy because of nonresponse (nonresponders) and subsequently entered the rollover study ETV-901, follow-up results, including resistance profile, are provided.

Cryptococcal meningoradiculitis: an atypical presentation after initiation of antiretroviral therapy.

Atypical presentations of cryptococcal infection have been described as clinical manifestations of immune reconstitution inflammatory syndrome (IRIS) in HIV-infected patients following commence of antiretroviral therapy (ART). The authors describe a patient presenting with cryptococcal meningoradiculitis two weeks after initiation of ART. In patients with advanced HIV disease, immune reconstitution induced by ART can precipitate onset of atypical clinical manifestations in those patients with latent cryptococcal infection of the central nervous system.

Two-year observation of the clinical efficacy in treating chronic hepatitis B Patients with Ganxian recipe and lamivudine.

OBJECTIVE: To evaluate the clinical efficacy of Ganxian recipe (GXR) and lamivudine (LVD) in a two-year treatment of chronic hepatitis B (CHB). METHODS: One hundred and twenty patients with CHB were randomly divided into the combinedly treated group (combined group) of 40 CHB patients who were treated with GXR combined with LVD. Another 40 CHB patients were treated with LVD alone (WM group), and still another 40 CHB patients were treated with GXR alone (TCM group). All these cases were randomly controlled and observed for two years. RESULTS: Comprehensive efficacy: Total effective rate of the combined group (complete response and partial response) was 92.5%, while that of the WM group was 67.5% and TCM group 57.5%, respectively, with the difference between them was significant (P < 0.01); after treatment, the hepatic functions (AST, ALT, SB) of the three groups were all reduced, and the reduction in the combined group was particularly significant in comparison with the WM group or TCM group, P < 0.05 or P < 0.01 respectively, suggesting that the effect in the combined group was better than that in the other two groups; the rate of tyrosine-methionine-aspartate-aspartate (YMDD) virus mutation: it was 7.5% in the combined group, 40.0% in the WM group, and 5.0% in the TCM group; liver fibrosis improvement parameter: after treatment, the results in the combined group got better than those in the other two groups. CONCLUSION: GXR could inhibit the appearance of YMDD after long-term application of LVD, and combined use has marked synergism.

To AIDS and back with Norvir, D4T, 3TC and nutritional therapies. An interview with Michael Golk.

AIDS: Michael Golk, a person with AIDS who is successfully maintaining a non-detectable viral load using Norvir combined with D4T and 3TC, describes his treatment regimen and use of nutritional supplements. Changes in Golk's nutritional supplement list (36 supplements were used) and the regimen and reasons for these changes are discussed. Changes are suggested to treat metabolic imbalances, such as high levels of triglycerides and high cholesterol, and to stimulate ATP production. The value of delavirdine vs. nevirapine in therapy is also discussed.^ieng