Lamivudine Monotherapy Research Articles

Immunological and virological outcomes in children on lamivudine monotherapy: A South African public sector experience

Background. In resource-limited settings, holding regimens such as lamivudine monotherapy (LAM) have been used to manage HIV-positive children failing combination antiretroviral therapy to mitigate the risk of drug resistance developing, while adherence barriers are addressed or when access to second- or third-line regimens is restricted. South African HIV treatment guidelines previously advocated the use of LAM to manage HIV-infected children with virological failure. However, the outcomes of patients on LAM compared with those who continued on a failing regimen have not been well described. Objectives. To investigate characteristics of a large cohort of children placed on LAM and their outcomes. Methods. This was a retrospective review of children with virological failure and the documented M184V drug resistance mutation who were placed on LAM v. a control group of children who continued on a failing regimen despite persistent virological failure. Virological and immunological outcomes of LAM were compared with those in patients who remained on a failing regimen. Results. A total of 179 children were included in the analysis, with 92 in the LAM group and 87 in the control group. The median (interquartile range (IQR)) age at baseline was 9.2 (5.4 - 12) years, the median CD4 count was 384 (184 - 622) cells/μL, and the median HIV viral load was 4.7 (IQR 3.7 - 5.3) log10. Twenty-two children (25.6%) in the LAM group and 15 (17.4%) in the control group experienced immunological deterioration. There was no statistical difference between the two groups with regard to overall time to immunological deterioration (log-rank p-value 0.4810). Conclusion. Given that a higher proportion of children in the LAM group experienced immunological failure, the LAM strategy may be a useful short-term one but should be restricted to children with limited treatment options. Managing children with virological failure will continue to be a challenge until improved adherence strategies are available.

The treatment outcome of chronic HBV infection among HBV/HIV co-infected and HBV mono-infected patients.

The aim of this study was to analyze the treatment response of hepatitis B virus (HBV) to lamivudine and tenofovir disoproxil fumarate in HBV/HIV co-infected patients in comparison to HBV mono-infected patients. This study was conducted at the University Hospital for Infectious and Tropical Diseases in Belgrade from January 2000 until December 2017 and included all patients with chronic hepatitis B who received antiviral therapy. All patients initially treated with lamivudine were switched to tenofovir if lamivudine failure occurred. A patient was considered to have achieved a full treatment response if the level of HBV DNA was lower than 20 IU/ml or undetectable. HBs and HBe antigen loss and HBs seroconversion were also monitored. After a mean duration of lamivudine-containing antiretroviral therapy (ART) of 4.87 ± 3.48 years and lamivudine mono-therapy of 4 ± 2.52 years, failure was recorded in 82.1% and 79.3% of patients, respectively. HBV viral loads were 20 ± 32 IU/ml and 3 ± 13 IU/ml after 2.49 ± 1.56 years of tenofovir-containing ART and 1.9 ± 1.13 years of tenofovir mono-therapy, respectively. Overall mean treatment duration, taking both lamivudine- and tenofovir-based regimens into account, was 4.18 ± 2.72 and 6.17 ± 3.63 years in the mono- and co-infected patients, respectively ( p = 0.02).

Use and Outcomes of Antiretroviral Monotherapy and Treatment Interruption in Adolescents With Perinatal HIV Infection in Asia

PurposeAntiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. MethodsRegional Asian data (2001–2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. ResultsOf 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. ConclusionsUntil challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.

What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes. We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models. Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively. The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.

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.

Lamivudine monotherapy as a holding regimen for HIV-positive children.

BackgroundIn resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes.MethodsWe describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART.FindingsWe included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3–14.6), duration on cART was 3.6 years (IQR 2.0–5.9) and median CD4 count was 605.5 cells/μL (IQR 427–901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7–55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3–73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART.InterpretationMost patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.

Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: a meta-analysis

BackgroundCurrently, there is no consensus on the efficacy and safety of lamivudine (LAM) plus tenofovir disoproxil fumarate (TDF) combination therapy versus lamivudine monotherapy in HBV/HIV coinfected patients.MethodsA comprehensive literature search was performed in English and Chinese databases. Both relevant dichotomous and continuous variables were extracted, and the combined outcomes were expressed as a risk ratio (RR) or a standard mean difference (SMD).ResultsEleven eligible studies were included in our analysis. For HBV-relevant outcomes, the proportion of patients with undetectable HBV, the rates of serum alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) loss were higher in the combination therapy group than the monotherapy group (RR = 1.42, 95% CI: 1.14–1.76, P = 0.002; RR = 1.36, 95% CI: 1.17–1.58, P < 0.0001; RR = 2.74, 95% CI: 1.20–6.22, P = 0.02). In addition, the rate of HIV RNA-negative conversion was higher in the combination therapy group than the monotherapy group (RR = 1.26, 95% CI: 1.11–1.42, P = 0.0003).ConclusionLAM plus TDF combination therapy was more efficacious than LAM monotherapy in HBV/HIV coinfected patients. As time passes, this difference becomes more pronounced.

A Multicenter Study of the Antiviral Efficacy of Entecavir Monotherapy Compared to Lamivudine Monotherapy in Children with Nucleos(t)ide-naïve Chronic Hepatitis B.

BackgroundThe aim of this study was to compare the long-term efficacy of entecavir (ETV) and lamivudine (LAM) therapy in children with chronic hepatitis B (CHB) who had not received nucleoside analogue treatment.MethodsIn this multicenter, retrospective study, we included pediatric CHB patients younger than 20 years who received ETV or LAM treatment for at least 12 months and had no concomitant diseases. All of the patients were followed up every 1 to 3 months. At each visit, the patients underwent clinical evaluation and biochemical testing.ResultsEight (53.3%), 14 (93.3%), and 2 (15.4%) of the ETV-treated patients achieved virologic suppression, alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) seroconversion, respectively, at 1 year. In the ETV group, the cumulative rate of virologic suppression at 3 years was 91.7%, which was significantly higher than that in the LAM group (P < 0.001). The mean duration of treatment before virologic suppression was shorter in the ETV group than in the LAM group (P = 0.040). The cumulative rate of seroconversion in the ETV group at 3 years was 39.4%, which was not significantly different from that in the LAM group (P = 0.439). The ETV group showed lower cumulate rates of virologic breakthrough (33.3% at 6 years) and genotypic mutation than the LAM group (P = 0.033 and P = 0.011, respectively).ConclusionETV is superior to LAM in pediatric CHB treatment because of its higher virologic suppression rate and lower cumulative rates of virologic breakthrough and genotypic mutation.

Lamivudine monotherapy in children and adolescents: The devil is in the detail.

Although expanded access to antiretroviral therapy (ART), and starting lifelong ART as soon as possible after diagnosis of HIV, have dramatically improved survival and reduced morbidity in HIV-infected children and adolescents, ~20% of children will develop virological failure (VF). Children and adolescents may be at higher risk of VF and drug resistance for a number of reasons, including prevention of mother-to-child exposure, reliance on a caregiver to administer ART, poor palatability of paediatric drugs, tuberculosis/HIV co-treatment in protease inhibitor (PI) (mainly lopinavir/ritonavir)-based regimens, and adolescence being associated with poor adherence. In children with VF, if adherence issues are addressed and re-suppression is not achieved, a switch to second- or third-line drugs may be indicated, which is the gold standard in management. However, in the face of ongoing adherence challenges, with potential accumulation of resistance mutations, limited treatment options due to extensive resistance and limited approved paediatric formulations, other strategies have been used. These include continuing a failing PI regimen, switching to a holding regimen (one or more nucleoside reverse transcriptase inhibitors) or discontinuing ART. Lamivudine monotherapy is a common choice when holding regimens are used, on the premise that the lamivudine-associated M184V resistance mutation reduces viral replication and may maintain clinical and immunological stability compared with discontinuing treatment altogether. However, this strategy is generally associated with immunological, and in some cases clinical, decline after starting lamivudine monotherapy. We discuss the pros and cons of using this therapy in children. We also propose guidance for using lamivudine monotherapy, suggesting clinical and immunological criteria for its use. Close monitoring and adherence support are required with this approach. Given many new emerging ART drugs and strategies, lamivudine monotherapy should be administered temporarily, while efforts to improve adherence are implemented. It should not be considered a default option in children with VF.

Impact of Protease Inhibitor-Based Anti-Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients.

Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p=0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p=0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p=0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p=0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.

Physician testing for HIV in patients treated with tenofovir disoproxil fumarate and lamivudine monotherapy for hepatitis B virus.

Previously we found that local patients were often not tested for HIV prior to commencing nucleoside/nucleotide reverse transcription inhibitor (NRTI) therapy for hepatitis B virus. We performed a national cross-sectional cohort study of physician practices via an online survey. A small majority (23/44; 52%) of participants reported always testing their hepatitis B virus patients for HIV prior to NRTI therapy, and 8/44 (18%) reported testing for HIV the majority of the time. Thirteen (30%) respondents reported testing only if risk factors were present. One physician reported a patient seroconverting to HIV while on TDF monotherapy.

Nucleoside analogs treatment delay the onset of hepatocellular carcinoma in patients with HBV-related cirrhosis.

Whether Nucleos(t)ide analogs(NA) treatment can delay the onset of HCC remains unclear. We retrospectively analyzed the clinical data of patients with HBV-related cirrhosis and HCC from 2000 to 2012. Cox proportional hazards model was used to explore the association between NA treatment and postponement of HCC development, the dependent variable was time interval from cirrhosis treatment towards the onset of HCC, and the covariates included age, sex, family history, compensation status at baseline. A total of 1155 HCC patients treated with NAs (n = 528, lamivudine, adefovir, entecavir) and non NA (n = 627) for more than 24 months before the occurrence of HCC were incorporated into the cohort. Compared with the non-NA group, NAs therapy was associated with delaying the onset of HCC in patients with cirrhosis. Significant factors were: adefovir treatment (n = 181; p = 0.0072; HR: 0.792; 90% CI: 0.687–0.914), entecavir treatment (n = 83; p = 0.0068; HR: 0.716; 90% CI: 0.585-0.877), lamivudine switched to adefovir treatment (n = 95, p = 0.0808; HR: 0.822; 90% CI: 0.684 to 0.989). But Lamivudine monotherapy was not a significant factor (n = 102; p = 0.6877; HR: 1.045; 90% CI: 0.873–1.250). Long-term NA treatment (> 6 months, except for lamivudine monotherapy) can delay the onset of HCC in patients with HBV-related cirrhosis, and applying high barrier NA to resistance is important in these patients.

Predominance of Hepatitis B Virus Genotype A Among Treated HIV Infected Patients Experiencing High Hepatitis B Virus Drug Resistance in Nairobi, Kenya

Hepatitis B virus (HBV)-HIV coinfections are becoming common with information on HBV genetic diversity and drug resistance still remaining elusive. To evaluate the HBV genetic diversity and drug resistance-associated mutations among drug-experienced HIV patients, the genetic analysis of the partial HBV-pol-reverse trancriptase gene was successfully sequenced from 13 samples. Analysis of the sequences showed that all (11) the sequences belonged to genotype A. Nucleos(t)ide drug resistance mutations were found in 6 patients. Five subjects had rtV173L, rtL180M, and rtM204V and one with rtL180M and rtM204V major mutations. HBV genotype A remains the most predominant genotype circulating in Nairobi city with detected high level of HBV drug resistance to lamivudine, telbivudine, and emtricitabine. The detected circulating HBV genotype A in Nairobi reflects its possible spread in the population with its origin being within the country. We suggest that patients should not be on lamivudine monotherapy. These individuals should be managed on combination of tenofovir plus lamivudine or emtricitabine therapy to prevent the emergence of HBV drug resistant variants alongside a continuous surveillance monitoring of drug resistance and HBV genotypes.

A CROSS-SECTIONAL STUDY OF HEPATITIS B VIRUS INFECTION IN HIV-INFECTED CHILDREN IN WINDHOEK, NAMIBIA

BackgroundHepatitis B virus (HBV) remains endemic in Africa and an important co-morbidity in the HIV epidemic. The HIV treatment guidelines of the World Health Organisation (WHO) recommend tenofovir−lamivudine (or emtricitabine)...

Effect of Shuanghu Qinggan Granule () and Yigan Yiqi Jieyu Granule () plus lamivudine on chronic hepatitis B patients: A randomized double-blind placebo-controlled trial.

To observe the clinical efficacy and safety of Shuanghu Qinggan Granule ( , SQG) plus Yigan Yiqi Jieyu Granule (, YYJG) combined with lamivudine (LAM) on chronic hepatitis B (CHB) patients. The study was a multicenter, randomized, double-blinded and parallel controlled trial. A total of 320 patients were randomly allocated into 2 groups equally: 160 patients (treatment group) were given SQG and YYJG combined with LAM; and 160 patients (control group) were given LAM plus Chinese herb placebo, respectively. Liver functions, hepatitis B envelop antigen (HBeAg) titer levels, and hepatitis B virus DNA (HBV-DNA) load were monitored. (1) In the 48th week, the treatment group showed superior HBeAg seroconversion rate than that in the control group (38.0% vs. 24.0%, P<0.05). (2) In the 48th week, the treatment group demonstrated lower HBeAg titer than that in the control group (P<0.05). (3) In the 12th, 24th, 48th week, there was no statistical significance in HBV-DNA response rate between the two groups. (4) In the 12th week, the level of glutamyl transpeptidase (GGT) was significantly decreased in the treatment group compared with the control group (P<0.05); in the 36th week, the levels of alanine aminotransferase and aspartate transaminase were significantly lower in the treatment group than those in the control group (P<0.05). The protocol of SQG and YYJG combined with LAM to treat CHB showed superior efficacy than LAM monotherapy.

Lamivudine Monotherapy: Experience of Medium-term Outcomes in HIV-infected Children Unable to Adhere to Triple Therapy.

HIV-infected children in resource-poor settings who fail or default from first-line antiretroviral therapy have limited alternative options. By preferentially selecting the M184V mutation, lamivudine monotherapy (LM) is occasionally used while awaiting patient readiness for second- or third-line therapy, but this strategy has not been widely studied. A retrospective review of all eligible LM events (≥3 months) from a cohort of two linked health facilities in the Eastern Cape Province, South Africa was undertaken. Events were disaggregated according to absolute CD4 count at initiation (Group 1: >200cells/μl, n=64; Group 2: ≤200cells/μl, n=7). Study endpoints were defined as a decline of absolute CD4 by ≥25% or to ≤200 cells/μl or World Health Organization stage 3 or 4 event (immunologic outcomes) or (re)initiation of second- or third-line therapy (real-world outcomes). Eligible LM events were identified among 71 children (56.4% male; median age at LM initiation 9.6 years). 71.8% (n = 51) had a drop in CD4 count of ≥25%, 15.6% (n = 10) of those whose CD4 counts had been >200 cells/μl dropped to ≤200 cells/μl and 8.1% (n = 6) experienced a stage 3 or 4 event; CD4 decreases and stage 3 or 4 events did not differ significantly between groups. No deaths were recorded. Children commencing LM with CD4 counts ≤200cells/μl had a shorter mean "real-world" duration of LM before switching to second/third line therapy (11.38 months vs. 26.1 months, P < 0.0001) and experienced immunologic outcomes at an earlier stage (5.29 vs. 9.2 months, P = 0.023). LM offers a potential alternative approach to antiretroviral therapy management in young patients pending availability and/or willingness to adhere to second- or third-line therapies but is associated with substantial immunologic decline. This strategy should be avoided in patients with CD4 ≤200 cells/μl.

Interruptions of antiretroviral therapy in children and adolescents with HIV infection in clinical practice: a retrospective cohort study in the USA.

IntroductionChanges in combination antiretroviral therapy (cART) throughout childhood challenge the continuity of paediatric HIV treatment. This study aimed to evaluate the prevalence of treatment interruption (TI), including lamivudine (3TC) monotherapy, and the relationship of TI to virologic and immunologic parameters in HIV-infected paediatric patients.MethodsNested within a prospective observational study of a city-wide cohort of HIV-infected persons in the District of Columbia, this sub-study collected retrospective data on antiretroviral therapy, enrolment (endpoint) and historic (lifelong) CD4 counts and HIV RNA viral load (VL) of the paediatric cohort. TI was defined as interruption of cART ≥4 consecutive weeks. Data on TI, including 3TC monotherapy TI (MTI), were collected. Descriptive statistics and univariate testing were used to compare children with TI and MTI to children on continuous treatment (CT).ResultsThirty-eight (28%) out of 136 enrolled children (median age=12.9 years) experienced TI, with 14 (37%) of those placed on 3TC MTI. Significantly lower endpoint median CD4 counts (598 cells/mm3 vs. 815 cells/mm3; p=0.003) and CD4% (27.5% vs. 33%; p=0.006) were observed in the TI cohort as compared to the CT cohort. The median endpoint VL in the overall TI cohort was ~4 times higher than among the CT cohort (1427 copies/mL vs. 5581 copies/mL; p<0.0001). After a median TI duration of one year, a majority (n=31; 82%) of patients with TI restarted cART, including 100% of those with total TI and 53% of those on MTI, respectively.ConclusionsIn our study, we observed high frequency of the TI in HIV in paediatric HIV clinical practice. All TIs, including 3TC MTI, were associated with significantly lower endpoint median CD4 counts and higher median VLs, as compared to CT in paediatric patients. The high frequency of TI and associated poor outcomes suggest a need for a better strategy in managing the course of the paediatric and adolescent cART.

Randomized, three-arm study to optimize lamivudine efficacy in hepatitis B e antigen-positive chronic hepatitis B patients.

Data about the efficacy of de novo combination therapies, or optimization strategy by adding the other drug based on the virological response at week 24 of low genetic barrier antiviral agents is still limited. This study aimed to compare the efficacy at week 104 of lamivudine monotherapy (MONO), lamivudine plus adefovir dipivoxil (ADV) combination therapy (COMBO), and lamivudine optimization strategy (OPTIMIZE). Adult patients without antiviral therapy within 6 months before screening with hepatitis B virus (HBV)-DNA ≥ 10(5) copies/mL, alanine aminotransferase 1.3-10 times upper limit of normal and compensated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) were randomized into three groups with 1:1:1 ratio. Patients in OPTIMIZE group started with lamivudine 100 mg q.d., and ADV 10 mg q.d. was added to suboptimal responders (HBV-DNA > 1000 copies/mL at week 24) from week 30 to week 104, whereas patients with early virological response (HBV-DNA ≤ 1000 copies/mL at week 24) continued MONO until week 104. For all the patients receiving MONO, ADV would be added if virological breakthrough was confirmed. At week 104, more patients in COMBO and OPTIMIZE groups achieved HBV-DNA < 300 copies/mL (53.3% [64/120] and 48.3% [58/120]), with less lamivudine resistance (0.8% and 6.7%) compared with MONO group (HBV-DNA < 300 copies/mL 34.8% [41/118], lamivudine resistance 58.5%). Patients under MONO with early virological response showed superior efficacy at week 104 (HBV-DNA < 300 copies/mL 73.1% [38/52], HBeAg seroconversion 40.4% [21/52]). All regimens were well tolerated. Combination therapy of lamivudine plus ADV exhibited effective viral suppression and relatively low resistance in HBeAg-positive CHB patients. In lamivudine-treated patients with suboptimal virological response at week 24, promptly adding on ADV is necessary to prevent resistance development.

Effects of nucleos(t)ide analogues initial treatment on virology and complications in hepatitis B virus related decompensated liver cirrhosis: a multicenter, prospective and observational study

Objective To evaluate the effects of nucleos(t)ide analogues initial treatment on virology and complications in hepatitis B virus (HBV) related decompensated liver cirrhosis. Methods From May 2012 to October 2013, a total of 209 patients with HBV related decompensated liver cirrhosis of 18 hospitals in China were enrolled. According to antiviral medicine taken by them, they were divided into entecavir (ETV) group (n=161), lamivudine (LAM) monotherapy or combined with adefovir (ADV) group (n=48, LAM 22 cases, LAM+ ADV 26 cases). During the 12-month follow-up period, Child-Pugh scores, the level of HBV DNA and complications of liver cirrhosis were documented every three months, the safety evaluation was also carried out. The t-test or chi-square test was performed for statistical analysis. Results In ETV group, before treatment and 12 months after treatment, Child-Pugh scores were 7.91±2.05 and 5.75±1.72, respectively, and the latter was lower than the former (t=10.130, P 0.05). The undetectable rates of HBV DNA gradually increased along with the treatment period. After 12 months treatment, the undetectable rate of HBV DNA of ETV group was 91.0%(61/67), and that of LAM alone or combined with ADV group was 87.5% (35/40), there was no significant difference between the two groups (P>0.05). Before treatment and 12 months after treatment, the incidences of ascites were 59.4% (82/138) and 15.0% (12/80) in ETV group, the latter was lower than the former (χ2=40.740, P 0.05). There was no significant difference in serum urea nitrogen, serum creatinine and estimated glomerular filtration rates between the two groups before treatment and at different time points after treatment (all P>0.05). Conclusion The efficacy and safety of ETV and LAM alone or combined with ADV are similar in patients with HBV related decompensated liver cirrhosis, however, the long-term efficacy should be identified by further clinical observation. Key words: Liver cirrhosis; Hepatitis B virus; Entecavir; Complications

Partial virological response to three different nucleotide analogues in naive patients with chronic hepatitis B

The definition of partial virological response (PVR) was proposed because of its clinical relevance. PVR relates to subsequent therapeutic failure which results in the modification of the regimen. Whether this rationale can be applied to all nucleotide analogues (NA) is not clear. This study was undertaken to analyze PVR influence on therapeutic outcomes during lamivudine, entecavir or tenofovir monotherapy in NA-naive patients with chronic hepatitis B in routine clinical practice. We retrospectively analyzed 150 NA-naive patients with chronic hepatitis B. These subjects received lamivudine, entecavir or tenofovir monotherapy between February 2001 and July 2013. Sixty-nine patients were treated with lamivudine, 35 with entecavir, and 46 with tenofovir. The median therapeutic duration was 19.5 (6-147) months. PVR rates at 24 weeks were similar among three NAs (lamivudine 33.3%, entecavir 35.0%, tenofovir 32.4%, P=0.981). For all three NAs, patients with a higher baseline viral load or HBeAg-positive status had a higher serum viral positive rate tested by polymerase chain reaction at week 24 and 48. Cumulative probability of virological breakthrough (VBR) for patients treated with lamivudine was 67% at 5 years, and PVR at 24 weeks was the independent risk factor for VBR (HR: 3.09; 95% CI: 1.09-8.74; P=0.034); also lamivudine treated patients older than 50 years seemed to have a tendency for VBR (HR: 2.80; 95% CI: 0.99-8.18; P=0.052). A majority of entecavir and tenofovir partial responders achieved and maintained virological response with prolonged monotherapy, except one entecavir treated patient who experienced VBR due to resistance mutations. Management strategy for lamivudine treatment should include adaptation of regimen according to PVR as an on-treatment response parameter due to its relation with unacceptably high VBR probability. Similar conclusion should not be directly related to entecavir or tenofovir treatment.