Hepatitis C treatment program in Maputo, Mozambique, the challenge of genotypes and key populations: A 5‐year retrospective analysis of routine programmatic data

Abstract Background and Aims Hepatitis C (HCV) programs face challenges, especially linked to key populations to achieve World Health Organization (WHO) goals of eliminating hepatitis. Médecins Sans Frontières and Mozambique's Ministry of Health first implemented HCV treatment in Maputo, in 2016 and harm reduction activities in 2017. Methods We retrospectively analyzed routine data of patients enrolled between December 2016 and July 2021. Genotyping was systematically requested up to 2018 and subsequently in cases of treatment failure. Sustainable virological response was assessed 12 weeks after the end of treatment by sofosbuvir‐daclatasvir or sofosbuvir‐velpatasvir. Results Two hundred and two patients were enrolled, with 159 (78.71%) males (median age: 41 years [interquartile range (IQR): 37.10, 47.00]). Risk factors included drug use (142/202; 70.29%). One hundred and eleven genotyping results indicated genotype 1 predominant (87/111; 78.37%). Sixteen patients presented genotype 4, with various subtypes. The people who used drugs and HIV coinfected patients were found more likely to present a genotype 1. Intention‐to‐treat analysis showed 68.99% (89/129) cure rate among the patients initiated and per‐protocol analysis, 88.12% (89/101) cure rate. Nineteen patients received treatment integrated with opioid substitution therapy, with a 100% cure rate versus 59.37% (38/64) for initiated ones without substitution therapy (p < 0.001). Among the resistance testing performed, NS5A resistance‐associated substitutions were found in seven patients among the nine tested patients and NS5B ones in one patient. Conclusion We found varied genotypes, including some identified as difficult‐to‐treat subtypes. People who used drugs were more likely to present genotype 1. In addition, opioid substitution therapy was key for these patients to achieve cure. Access to second‐generation direct‐acting antivirals (DAAs) and integration of HCV care with harm reduction are crucial to program effectiveness.

[1]  P. Mateu-Gelabert,et al.  Accessible Hepatitis C Care for People Who Inject Drugs: A Randomized Clinical Trial. , 2022, JAMA internal medicine.

[2]  M. Katz,et al.  Curing Hepatitis C-Requires More Than a Prescription. , 2022, JAMA Internal Medicine.

[3]  J. Ward,et al.  Interventions to enhance testing, linkage to care, and treatment initiation for hepatitis C virus infection: a systematic review and meta-analysis. , 2022, The lancet. Gastroenterology & hepatology.

[4]  P. Grant,et al.  Safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for re-treatment of chronic hepatitis C virus infection in patients with previous direct-acting antiviral treatment failure in Rwanda (SHARED-3): a single-arm trial. , 2022, The lancet. Gastroenterology & hepatology.

[5]  Dao Sen Wang,et al.  Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals , 2022, JHEP reports : innovation in hepatology.

[6]  E. Thomson,et al.  Hepatitis C virus in sub-Saharan Africa: a long road to elimination. , 2021, The Lancet Gastroenterology and Hepatology.

[7]  N. Luhmann,et al.  New WHO guidance for country validation of viral hepatitis B and C elimination. , 2021, The lancet. Gastroenterology & hepatology.

[8]  E. Thomson,et al.  Non-epidemic HCV genotypes in low- and middle-income countries and the risk of resistance to current direct-acting antiviral regimens , 2021, Journal of hepatology.

[9]  S. Yerly,et al.  Efficacy and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C infection without cirrhosis or with compensated cirrhosis (STORM-C-1): interim analysis of a two-stage, open-label, multicentre, single arm, phase 2/3 trial , 2021, The lancet. Gastroenterology & hepatology.

[10]  S. Balkan,et al.  Decentralised hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system. , 2021, The lancet. Gastroenterology & hepatology.

[11]  C. Sarrazin Treatment failure with DAA therapy: importance of resistance. , 2021, Journal of hepatology.

[12]  S. Luchters,et al.  Prevalence of HIV, viral hepatitis B/C and tuberculosis and treatment outcomes among people who use drugs: Results from the implementation of the first drop-in-center in Mozambique. , 2021, The International journal on drug policy.

[13]  H. Raymond,et al.  Low engagement in HIV services and progress through the treatment cascade among key populations living with HIV in Mozambique: alarming gaps in knowledge of status , 2020, BMC Public Health.

[14]  J. Pawlotsky,et al.  EASL recommendations on treatment of hepatitis C - Final update of the series. , 2020, Journal of hepatology.

[15]  P. Simmonds,et al.  Efficacy of NS5A inhibitors against unusual and potentially difficult-to-treat HCV subtypes commonly found in sub Saharan Africa and South East Asia. , 2020, Journal of hepatology.

[16]  K. Lacombe,et al.  Is resistance to direct-acting antivirals in sub-Saharan Africa a threat to HCV elimination? Recommendations for action. , 2019, Journal of hepatology.

[17]  N. Schaad,et al.  High prevalence of HIV, HBsAg and anti-HCV positivity among people who injected drugs: results of the first bio-behavioral survey using respondent-driven sampling in two urban areas in Mozambique , 2019, BMC Infectious Diseases.

[18]  J. Pawlotsky DAA failures in African patients with "unusual" HCV subtypes: Hey! Didn't you know there was another world? , 2019, Journal of hepatology.

[19]  P. Simmonds,et al.  Suboptimal SVR rates in African patients with atypical genotype 1 subtypes: Implications for global elimination of hepatitis C , 2019, Journal of hepatology.

[20]  A. Puren,et al.  Understanding hepatitis B, hepatitis C and HIV among people who inject drugs in South Africa: findings from a three-city cross-sectional survey , 2019, Harm Reduction Journal.

[21]  Joshua B. Singer,et al.  Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments , 2019, Hepatology.

[22]  J. Mukherjee,et al.  Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial. , 2019, The lancet. Gastroenterology & hepatology.

[23]  H. Bygrave,et al.  Extremely low hepatitis C prevalence among HIV co-infected individuals in four countries in sub-Saharan Africa , 2018, AIDS.

[24]  Jean-Michel Pawlotsky,et al.  EASL Recommendations on Treatment of Hepatitis C 2018. , 2018, Journal of hepatology.

[25]  Francesca Ceccherini-Silberstein,et al.  Hepatitis C virus drug resistance associated substitutions and their clinical relevance: Update 2018. , 2018, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[26]  S. Nsanzimana,et al.  Controlling hepatitis C in Rwanda: a framework for a national response , 2017, Bulletin of the World Health Organization.

[27]  A. Luetkemeyer,et al.  Understanding Hepatitis C Virus Drug Resistance: Clinical Implications for Current and Future Regimens. , 2017, Topics in antiviral medicine.

[28]  J. Pawlotsky,et al.  EASL Recommendations on Treatment of Hepatitis C 2016. , 2017, Journal of hepatology.

[29]  F. Nevens,et al.  Global genotype distribution of hepatitis C viral infection among people who inject drugs. , 2016, Journal of hepatology.

[30]  A. Flaxman,et al.  Global Distribution and Prevalence of Hepatitis C Virus Genotypes , 2014, Hepatology.

[31]  O. Pybus,et al.  Phylogeography and epidemic history of hepatitis C virus genotype 4 in Africa , 2014, Virology.

[32]  V. Paradis,et al.  Comparison of transient elastography (FibroScan), FibroTest, APRI and two algorithms combining these non‐invasive tests for liver fibrosis staging in HIV/HCV coinfected patients: ANRS CO13 HEPAVIH and FIBROSTIC collaboration , 2014, HIV medicine.

[33]  N. Luhmann,et al.  An urgent need to scale-up injecting drug harm reduction services in Tanzania: prevalence of blood-borne viruses among drug users in Temeke District, Dar-es-Salaam, 2011. , 2013, The International journal on drug policy.

[34]  Peter Vickerman,et al.  Understanding the trends in HIV and hepatitis C prevalence amongst injecting drug users in different settings--implications for intervention impact. , 2012, Drug and alcohol dependence.

[35]  P. Harris,et al.  Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support , 2009, J. Biomed. Informatics.

[36]  C. Antunes,et al.  HIV/HCV coinfection in Infectious Disease Units in Mozambique and Brazil: a comparative study. , 2008, Revista da Sociedade Brasileira de Medicina Tropical.

[37]  J. Montaner,et al.  A review of barriers and facilitators of HIV treatment among injection drug users , 2008, AIDS.

[38]  V. de Lédinghen,et al.  Epidemiological characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infection , 2007, Journal of viral hepatitis.

[39]  B. Bacon,et al.  Infection with Hepatitis C Virus Genotype 4 in the United States , 2004, Journal of clinical gastroenterology.

[40]  C. Dolea,et al.  World Health Organization , 1949, International Organization.