Hepatitis B virus drug resistance mutations in HIV/HBV co-infected children in Windhoek, Namibia

CITATION: Tchuem, C. R. T., et al. 2020. Hepatitis B virus drug resistance mutations in HIV/HBV co-infected children in Windhoek, Namibia. PLoS ONE, 15(9):e0238839, doi:10.1371/journal.pone.0238839.The original publication is available at https://journals.plos.org/plosone/Publication of this article was funded by the Stellenbosch University Open Access FundENGLISH ABSTRACT: In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238839Publisher's versio

Task-shifting point-of-care CD4+ testing to lay health workers in HIV care and treatment services in Namibia

Introduction: Access to CD4+ testing remains a common barrier to early initiation of antiretroviral therapy among persons living with HIV/AIDS in low- and middle-income countries. The feasibility of task-shifting of point-of-care (POC) CD4+ testing to lay health workers in Namibia has not been evaluated. Methods: From July to August 2011, Pima CD4+ analysers were used to improve access to CD4+ testing at 10 selected public health facilities in Namibia. POC Pima CD4+ testing was performed by nurses or lay health workers. Venous blood samples were collected from 10% of patients and sent to centralised laboratories for CD4+ testing with standard methods. Outcomes for POC Pima CD4+ testing and patient receipt of results were compared between nurses and lay health workers and between the POC method and standard laboratory CD4+ testing methods. Results: Overall, 1429 patients received a Pima CD4+ test; 500 (35.0%) tests were performed by nurses and 929 (65.0%) were performed by lay health workers. When Pima CD4+ testing was performed by a nurse or a lay health worker, 93.2% and 95.2% of results were valid (p = 0.1); 95.6% and 98.1% of results were received by the patient (p = 0.007); 96.2% and 94.0% of results were received by the patient on the same day (p = 0.08). Overall, 97.2% of Pima CD4+ results were received by patients, compared to 55.4% of standard laboratory CD4+ results (p < 0.001). Conclusions: POC CD4+ testing was feasible and effective when task-shifted to lay health workers. Rollout of POC CD4+ testing via task-shifting can improve access to CD4+ testing and retention in care between HIV diagnosis and antiretroviral therapy initiation in low- and middle-income countries

Nurse task shifting for antiretroviral treatment services in Namibia: implementation research to move evidence into action.

BackgroundEvidence from several sub-Saharan countries support nurse-initiated antiretroviral treatment as a feasible alternative to doctor-led models characteristic of early responses to the HIV epidemic. However, service delivery models shown to be effective in one country may not be readily adopted in another. This study used an implementation research approach to assist policy makers and other stakeholders to assess the acceptability and feasibility of task shifting in the Namibian context.MethodsThe Namibian Ministry of Health and Social Services implemented a Task Shifting Demonstration Project (TSDP) at 9 sites at different levels of the health system. Six months after implementation, a mixed methods evaluation was conducted. Seventy semi-structured interviews were conducted with patients, managers, doctors and nurses directly involved with the TSDP. Physician-evaluators observed and compared health service provision between doctors and nurses for 40 patients (80 observations), documenting performance in agreement with the national guidelines on 13 clinical care indicators.ResultsDoctors, nurses, and patients interviewed believed task shifting would improve access to and quality of HIV services. Doctors and nurses both reported an increase in nurses' skills as a result of the project. Observation data showed doctors and nurses were in considerable agreement (>80%) with each other on all dimensions of HIV care and ≥90% on eight dimensions. To ensure success of national scale-up of the task shifting model, challenges involving infrastructure, on-going mentoring, and nursing scope of practice should be anticipated and addressed.ConclusionIn combination with findings from other studies in the region, data from the TSDP provided critical and timely information to the Namibian Ministry of Health and Social Services, thus helping to move evidence into action. Small-scale implementation research projects enable stakeholders to learn by doing, and provide an opportunity to test and modify the intervention before expansion

Select demographic and clinical characteristics of sampled patients, sero-survey of <i>Cryptococcus</i> antigenemia among HIV-infected adults with advanced immunosuppression in Namibia, 2013–14.

<p>Select demographic and clinical characteristics of sampled patients, sero-survey of <i>Cryptococcus</i> antigenemia among HIV-infected adults with advanced immunosuppression in Namibia, 2013–14.</p

Prevalence and correlates of CrAg positivity among HIV-infected adults with advanced immunosuppression in Namibia, 2013–14.

<p>Prevalence and correlates of CrAg positivity among HIV-infected adults with advanced immunosuppression in Namibia, 2013–14.</p

Agreement Found During Clinical Observations (95% CI).

<p>Agreement Found During Clinical Observations (95% CI).</p

Estimated Prevalence of <i>Cryptococcus</i> Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment

<div><p>Background</p><p>Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4⁺ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies.</p><p>Methods</p><p>The study design was cross-sectional. De-identified plasma specimens collected for routine CD4⁺ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4⁺ counts <200 cells/μL were sampled and tested for CrAg using the IMMY^® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4⁺ count.</p><p>Results</p><p>A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32–46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4⁺ counts of CD4⁺<100 cells/μL and 100–200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50–200 (2.2%).</p><p>Conclusion</p><p>This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4⁺<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4⁺<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.</p></div

Location of Task Shifting Doctors and Nurses.

<p>*No paired observation possible between doctor and nurse at this hospital.</p

Task shifting demonstration project sites in Namibia.

<p>Task shifting demonstration project sites in Namibia.</p