Antivirals for prevention of hepatitis B virus mother-to-child transmission in human immunodeficiency virus positive pregnant women co-infected with hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV)-human Immunodeficiency virus (HIV) co-infection promotes an aggressive disease course of HBV infection. In the only available non-Cochrane systematic review on antiviral therapy during pregnancy for prevention of mother-to-child transmission of HBV, none of the women studied had HBV-HIV co-infection but were either HBV- or HIV-seropositive. Treatment of HBV alone may develop HIV-strains that are resistant to non-nucleoside reverse transcriptase inhibitors. Accordingly, co-treatment of the HIV infection is recommended. OBJECTIVES: To evaluate the benefits and harms of tenofovir-based antiviral combination regimens versus placebo, tenofovir alone, or non-tenofovir-based antiviral regimen either alone or in combination with HBV for the prevention of mother-to-child transmission of HBV in HIV-positive pregnant women co-infected with HBV. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, LILACS (Bireme), Science Citation Index Expanded (Web of Science), and Conference Proceedings Citation Index-Science (Web of Science) on 30 January 2023. We manually searched the reference lists of included trials, searched on-line trial registries, and contacted experts in the field and pharmaceutical companies for any further potential trials. SELECTION CRITERIA: We aimed to include randomised clinical trials comparing tenofovir-based antiviral combination regimens (anti-HIV regimen with lopinavir-ritonavir therapy, or any other antiviral therapy, and two drugs with activity against HBV, specifically, tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), plus lamivudine or emtricitabine) with placebo alone, or tenofovir alone, or non-tenofovir-based antiviral regimen (zidovudine, lamivudine, telbivudine, emtricitabine, entecavir, lopinavir-ritonavir, or any other antiviral therapy) either alone or in combination with at least two other antivirals. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcomes included all-cause infant mortality, proportion of infants with serious adverse events, proportion of infants with HBV mother-to-child transmission, all-cause maternal mortality, and proportion of mothers with serious adverse events. Secondary outcomes included proportion of infants with adverse events not considered serious, proportion of mothers with detectable HBV DNA (deoxyribonucleic acid) (before delivery), maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. We used RevMan Web to carry out analyses and presented results, where feasible, using a random-effects model and risk ratios (RR) with 95% confidence intervals (CIs). We performed sensitivity analysis. We assessed risk of bias using predefined domains, assessed the certainty of the evidence using GRADE, controlled risk of random errors with Trial Sequential Analysis, and presented outcome results in a summary of findings table. MAIN RESULTS: Five completed trials were included, of which four trials contributed data to one or more of the outcomes. They included a total of 533 participants randomised to tenofovir-based antiviral combination regimens (196 participants) versus control (337 participants). The control groups received non-tenofovir-based antiviral regimens either as zidovudine alone (three trials) or as a combination of zidovudine, lamivudine and lopinavir-ritonavir (five trials). None of the trials used placebo or tenofovir alone. All trials were at unclear risk of bias. Four trials used intention-to-treat analyses. In the remaining trial, two participants in the intervention group and two in the control group were lost to follow-up. However, the outcomes of these four participants were not described. Tenofovir-based antiviral combination regimen versus control We are very uncertain about the effect of a tenofovir-based antiviral combination regimen versus control on all-cause infant mortality (RR 2.24, 95% CI 0.72 to 6.96; participants = 132; trials = 1; very low-certainty evidence); proportion of infants with serious adverse events (RR 1.76, 95% CI 1.27 to 2.43; participants = 132; trials = 1; very low-certainty evidence), and proportion of mothers with serious adverse events (RR 0.90, 95% CI 0.62 to 1.32; participants = 262; trials = 2; very low-certainty evidence). No trial reported data on the proportion of infants with HBV mother-to-child transmission and all-cause maternal mortality. We are also very uncertain about the effect of tenofovir-based antiviral combination regimens versus control on the proportion of infants with adverse events not considered serious (RR 0.94, 95% CI 0.06 to 13.68; participants = 31; trials = 1; very low-certainty evidence), and proportion of mothers with detectable HBV DNA (before delivery) (RR 0.66, 95% CI 0.42 to 1.02; participants = 169; trials = 2; very low-certainty evidence). No trial reported data on maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion (before delivery) and maternal adverse events not considered serious. All trials received support from industry. AUTHORS' CONCLUSIONS: We do not know what the effects of tenofovir-based antiviral combination regimens are on all-cause infant mortality, proportion of infants with serious adverse events and proportion of mothers with serious adverse events, proportion of infants with adverse events not considered serious, and proportion of mothers with detectable HBV DNA before delivery because the certainty of evidence was very low. Only one or two trials, with insufficient power, contributed data for analyses. We lack randomised clinical trials at low risk of systematic and random errors, and fully reporting all-cause infant mortality, serious adverse events and reporting on clinical and laboratory outcomes, such as infants with HBV mother-to-child transmission, all-cause maternal mortality, maternal hepatitis B e antigen (HBeAg) to HBe-antibody seroconversion before delivery and maternal adverse events not considered serious.

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria.

Background: Chronic lymphocytic leukaemia is a relatively common haematological malignancy affecting older adults, accounting for about 20% of haematological malignancies in Nigeria. Diagnosis of this disease depends on the demonstration of clonal lymphocytosis > 5 × 109/L with a characteristic immunophenotypic pattern amidst other clinical and laboratory features. Objectives: To determine the predominant clinical and laboratory features of CLL at presentation and their relationship with patient survival. This study also aims at examining the relationship between treatment protocol and outcome. Methods: This is a retrospective study with 8 years data (2010-2018) collected from four different centers. Data was analyzed using SPSS 20.0. Results: There were a total of 97 cases, with a male: female ratio of 1.1:1. The median age at presentation was 59 years. Approximately 55% of the patients presented at Binet stage C, with splenomegaly in 93.2% and 78% were anaemic. The mean white cell count was 137.9 ± 14.7 × 109/L, with a median absolute lymphocyte count of 86 × 109/L. The commonest treatment regimen was chlorambucil and prednisolone and males had a superior response. The number of chemotherapy cycles, serum alkaline phosphatase and aspartate transaminase correlated positively with duration of survival. Mortality rate over the five year period was 14.3%. Conclusion: CLL was found to present in younger patients when compared to previous studies with a median age of 57 years at diagnosis. Our study showed a slight female preponderance and better response to therapy in males. Majority of the patients presented in Binet stage C and were treated with chlorambucil-based drug combinations compared to more current treatment with Fludarabine-based combinations. A high serum alanine transaminase and alkaline phosphatase was found to positively correlate with survival amongst this patient population.