Atypical hepatitis B virus serology profile—hepatitis B surface antigen-positive/hepatitis B core antibody-negative—in hepatitis B virus/HIV coinfected individuals in Botswana

DATA AVAILABILITY : The data presented in this study are available upon request from the corresponding author. The data are not publicly available as the sequences are currently being analyzed for other objectives of the bigger project.BACKGROUND : Hepatitis B core antibodies (anti-HBc) are a marker of hepatitis B virus (HBV) exposure; hence, a normal HBV serology profile is characterized by HBV surface antigen (HBsAg) and anti-HBc positivity. However, atypical HBV serologies occur, and we aimed to determine the prevalence of an atypical profile (HBsAg+/anti-HBc-) in a cohort of people with HIV-1 (PWH) in Botswana. METHODS : Plasma samples from an HIV-1 cohort in Botswana (2013–2018) were used. The samples were screened for HBsAg and anti-HBc. Next-generation sequencing was performed using the GridION platform. The Wilcoxon rank-sum test and Chi-squared tests were used for the comparison of continuous and categorical variables, respectively. RESULTS : HBsAg+/anti-HBc- prevalence was 13.7% (95% CI 10.1–18.4) (36/263). HBsAg+/anti-HBc- participants were significantly younger (p < 0.001), female (p = 0.02) and ART-naïve (p = 0.04) and had a detectable HIV viral load (p = 0.02). There was no statistically significant difference in the number of mutations observed in participants with HBsAg+/anti-HBc- vs. those with HBsAg+/anti-HBc+ serology. CONCLUSIONS : We report a high HBsAg+/anti-HBc- atypical serology profile prevalence among PWH in Botswana. We caution against HBV-testing algorithms that consider only anti-HBc+ samples for HBsAg testing, as they are likely to underestimate HBV prevalence. Studies to elucidate the mechanisms and implications of this profile are warranted.Wellcome Trust and the National Institutes of Health (NIH) Common Fund.https://www.mdpi.com/journal/virusesSchool of Public Management and Administration (SPMA

Community dialogue to enhance understanding of beliefs, behaviours and barriers to care for people living with liver disease and HBV infection in KwaZulu Natal, South Africa

INTRODUCTION: The World Health Organisation (WHO) has set targets for the elimination of Hepatitis B virus (HBV), which include preventing new infections and reducing deaths. We explored beliefs, behaviours and barriers to diagnosis, prevention and treatment for people living with HBV infection (PLWHB) and those with liver disease in a rural South African population in KwaZulu-Natal, to gather information to inform research and support the development of improved clinical and public health services. METHODS: Using an interdisciplinary approach (combining public engagement, social science, clinical and laboratory team members) we conducted a community dialogue with members of the Africa Health Research Institute (AHRI) Community Advisory Board (CAB). Notes from the discussions were used to write up an account from which themes were identified during a team debrief session for data analysis. RESULTS: There was a lack of knowledge and awareness of HBV infection and transmission and prevention amongst CAB members, also reported among community members and healthcare workers. The participants recognised liver disease symptoms. Perceived causes of liver disease reported by the CAB were alcohol and non-adherence to HIV treatment. Barriers to care included stigma, poverty, and delays in referrals for HBV diagnosis and management. CONCLUSION: Understanding barriers to care is important to shape future services for diagnosis, treatment and prevention of HBV and liver disease which are accessible, affordable and acceptable to the local population. Education, awareness and advocacy for improved liver health care pathways are required to make them effective for local communities

Chronic and Occult Hepatitis B Virus Infection in Pregnant Women in Botswana

The hepatitis B virus (HBV) is a global problem; however, the burden of HBV infection in pregnant women in Botswana is unknown. We sought to determine the prevalence of chronic and occult HBV infection in human immunodeficiency virus (HIV)-infected and -uninfected pregnant women in Botswana. Samples from 752 pregnant women were tested for hepatitis B surface antigen (HBsAg), and HBsAg-positive samples were tested for hepatitis B e antigen (HBeAg) and HBV DNA load. Samples that were HBsAg negative were screened for occult HBV infection by determining the HBV DNA load. HBV genotypes were determined based on a 415-base-pair fragment of the surface gene. Among the 752 women tested during pregnancy or early postpartum, 16 (2.1%) (95% confidence interval (CI): 2.0–2.2) were HBsAg-positive. The prevalence of chronic HBV infection was higher (3.1%) among HIV-infected (95% CI: 3.0–3.2) compared with HIV-uninfected women (1.1%) (95% CI: 1.07–1.1, p = 0.057). Among the 622 HBsAg-negative women, the prevalence of occult HBV infection was 6.6% (95% CI: 6.5–6.7). Three of thirteen HBsAg-positive participants were HBeAg-positive, and all were HIV-negative. Of the 11 maternal samples successfully genotyped, five (45.5%) were genotype D3, five (45.5%) were genotype A1, and one was genotype E (9%). Low and similar proportions of HIV-infected and -uninfected pregnant women in Botswana had occult or chronic HBV infection. We identified a subset of HIV-negative pregnant women who had high HBV DNA levels and were HBeAg-positive, and thus likely to transmit HBV to their infants

Correction: Youth and healthcare workers' perspectives on the feasibility and acceptability of self-testing for HIV, Hepatitis and Syphilis among young people: Qualitative findings from a pilot study in Gaborone, Botswana.

[This corrects the article DOI: 10.1371/journal.pone.0288971.]

High Rates of Occult Hepatitis B Virus Infection in HIV-Positive Individuals Initiating Antiretroviral Therapy in Botswana

Abstract Background: Hepatitis B surface antigen (HBsAg)–negative but hepatitis B virus (HBV) DNA-positive infection—known as occult hepatitis B infection (OBI)—occurs in 1% to >15% of HIV-positive individuals in the United States and South Africa, respectively. However, there are no data on OBI from Botswana, a country known to be hyperendemic for chronic HBV infection and to have a significant HIV burden. Methods: Two hundred seventy-two adults enrolled in an HIV treatment study of tenofovir/emtricitabine as the nucleoside backbone who were previously determined to be HBsAg negative were tested for HBV DNA at baseline and 1 year after initiation of highly active antiretroviral therapy (HAART). Results: HBV DNA was detected in 72 of 272 (26.5%). Six individuals (8.3%) had HBV DNA levels greater than 200 IU/mL, and the highest viral load was 3280 IU/mL. Of 65 participants with OBI evaluated at 12 months after initiating HAART, only 1 (1.5%) had detectable HBV DNA. Conclusions: Occult HBV infection is quite common in HIV-infected patients in Botswana, although its impact on the course of HIV disease progression is unknown. The suppression of occult HBV DNA levels by tenofovir/emtricitabine suggests an effective therapeutic option, although the long-term suppressive abilities remain unstudied

Youth and healthcare workers' perspectives on the feasibility and acceptability of self-testing for HIV, Hepatitis and Syphilis among young people: Qualitative findings from a pilot study in Gaborone, Botswana

Nambusi K, Gbolahan A, Maureen S-M, et al. Youth and healthcare workers' perspectives on the feasibility and acceptability of self-testing for HIV, Hepatitis and Syphilis among young people: Qualitative findings from a pilot study in Gaborone, Botswana. PLoS ONE. 2023;18(7): e0288971.INTRODUCTION: Little is known regarding the attitudes and perspectives of young people and healthcare workers in Botswana about dual self-testing for HIV and STIs including its acceptability, or their perceptions of the opportunities and limitations of this approach.; METHODS: From July to November 2021, 25 young people and 6 healthcare workers were purposively sampled for in-depth telephone interviews conducted in English or Setswana. The interviews followed a semi-structured topic guide, were audio recorded, transcribed, and analysed thematically using deviant case and constant comparative techniques. The study was part of a pilot project evaluating dual self-testing for HIV and STIs among young people in Gaborone.; RESULTS: We found that most of the young people were already aware of their HIV status and were motivated to participate in self-testing mainly because they were interested in learning their STI status. Whilst most were excited about the autonomy and convenience offered by self-testing, some participants expressed nervousness particularly of the finger-prick process, and preferred healthcare worker-administered tests. Both young people and healthcare workers raised concerns about the potential negative mental health outcomes of unexpected test results and emphasized the importance of pre- and post-test counselling and seamless linkage to care.; CONCLUSION: Dual self-testing for HIV and STIs has the potential to empower young people to take control of their sexual health. However, it is crucial to ensure that proper support and counselling services are in place, along with effective mechanisms for linkage to care. This study emphasizes the importance of integrating pre- and post-test counselling into self-testing programs to ensure that young people feel adequately supported throughout the testing process. By doing so, self-testing can become a valuable tool for improving the sexual health outcomes of young people in Botswana. Copyright: © 2023 Nambusi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Correction: Immunological non-response and low hemoglobin levels are predictors of incident tuberculosis among HIV-infected individuals on Truvada-based therapy in Botswana.

[This corrects the article DOI: 10.1371/journal.pone.0192030.]

Immunological non-response and low hemoglobin levels are predictors of incident tuberculosis among HIV-infected individuals on Truvada-based therapy in Botswana

Background: There is a high burden of tuberculosis (TB) in HIV antiretroviral programmes in Africa. However, few studies have looked at predictors of incident TB while on Truvada-based combination antiretroviral therapy (cART) regimens. Methods: We estimated TB incidence among individuals enrolled into an observational cohort evaluating the efficacy and tolerability of Truvada-based cART in Gaborone, Botswana between 2008 and 2011. We used Cox proportional hazards regressions to determine predictors of incident TB. Results: Of 300 participants enrolled, 45 (15%) had a diagnosis of TB at baseline. During 428 person-years (py) of follow-up, the incidence rate of TB was 3.04/100py (95% CI, 1.69–5.06), with 60% of the cases occurring within 3 months of ART initiation. Incident cases had low baseline CD4+ T cell counts (153cells/mm3 [Q1, Q3: 82, 242]; p = 0.69) and hemoglobin levels (9.2g/dl [Q1, Q3: 8.5,10.1]; p<0.01). In univariate analysis, low BMI (HR = 0.73; 95% CI 0.58–0.91; p = 0.01) and hemoglobin levels <8 g/dl (HR = 10.84; 95%CI: 2.99–40.06; p<0.01) were risk factors for TB. Time to incident TB diagnosis was significantly reduced in patients with poor immunological recovery (p = 0.04). There was no association between baseline viral load and risk of TB (HR = 1.75; 95%CI: 0.70–4.37). Conclusion: Low hemoglobin levels prior to initiation of ART are significant predictors of incident tuberculosis. Therefore, there is potential utility of iron biomarkers to identify patients at risk of TB prior to initiation on ART. Furthermore, additional strategies are required for patients with poor immunological recovery to reduce excess risk of TB while on ART

Molecular characterisation of hepatitis B virus in HIV-1 subtype C infected patients in Botswana

Background: Hepatitis B virus (HBV) is a major global health problem especially in sub-Saharan Africa and in East Asia. Ten hepatitis B virus genotypes have been described that differ by geographic distribution, disease progression, and response to treatment. Escape mutations within the surface open reading frame (ORF) affect HBV antigenicity leading to failures in diagnosis, vaccine and hepatitis B immunoglobulin therapy. However, the molecular characteristics of HBV in Botswana, a highly endemic country, are unknown. We describe the molecular characteristics of HBV and prevalence of escape mutants among HIV/HBV coinfected individuals Botswana. Methods: DNA was extracted from archived plasma samples from 81 HIV/HBV co-infected participants from various clinical studies at the Botswana Harvard AIDS Institute Partnership. A 415 base pair (bp) fragment of the polymerase gene was amplified by semi-nested PCR. In a subset of samples, a 2100 bp fragment was amplified. The PCR product was genotyped using Big Dye sequencing chemistry and the sequences were analysed for genotypes and mutations. Results: Of the 81 samples included, 70 (86 %) samples were successfully genotyped. Genotype A was found in 56 (80 %) participants, D in 13 (18.6 %), and 1 (1.4 %) was genotype E. Escape mutations previously linked with failure of diagnosis or escaping active vaccination and passive immunoglobulin therapy were detected in 12 (17.1 %) participants at positions 100, 119, 122, 123, 124, 126, 129, 130, 133, 134 and 140 of the S ORF. Genotypes and escape mutations were not significantly associated with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST platelet ratio index (APRI). Conclusion: Genotypes A, D and E were found in this cohort of HIV coinfected patients in Botswana, consistent with the findings from the sub-Saharan Africa region. Some escape mutations which have previously been associated with diagnosis failure, escaping vaccine and immunoglobulin therapy were also observed and are important in guiding future policies related to vaccine implementation, therapeutic guidelines, and diagnostic guidelines. They are also important for identifying patients who are at an increased risk of disease progression and to choose optimal therapy. Future research should focus on determining the clinical significance of the different HBV genotypes and mutations found in this population