Achieving a high cure rate with direct-acting antivirals for chronic Hepatitis C virus infection in Cameroon: a multi-clinic demonstration project.

OBJECTIVES: Highly effective direct-acting antivirals (DAAs) for Hepatitis C treatment are largely inaccessible in sub-Saharan Africa. Data on treatment feasibility and outcomes in clinical settings are limited. We assessed the feasibility of achieving a high (≥90%) cure rate with DAAs in six gastroenterology clinics in Cameroon. METHODS: Patients with chronic Hepatitis C virus (HCV) infection were treated for 12 or 24 weeks with ledipasvir/sofosbuvir, ledipasvir/sofosbuvir/ribavirin or sofosbuvir/ribavirin, depending on the stage of liver disease and HCV genotype. The cure rate was defined as the proportion of patients with a sustained virological response 12 weeks after treatment completion (SVR12) among all treatment completers. RESULTS: We identified 190 HCV RNA positive patients between September-2017 and August-2018, 161 (84.7%) of whom started treatment. 105 (65.2%) were female, median age was 61.3 years [IQR = 55.9-66.9] and 11 (6.8%) were HIV-positive. Median plasma HCV RNA was 6.0 log10 IU/mL [IQR = 5.6-6.4]. HCV genotypes identified were 1 (34.8%), 2 (13.7%), 4 (50.9%), 1 and 4 (0.6%); 46 (28.6%) strains of 160 single-genotype infections were non-subtypeable. Of 158 treatment completers, 152 (96.2%, 95%CI = 91.9-98.6%) achieved SVR12. Six patients did not achieve SVR12: five carried HCV with NS5A resistance mutations and one with NS5B resistance mutations. Three patients died before and two after treatment completion. The most common adverse events were asthenia (12.0%), headache (11.4%) and dizziness (18.9%). CONCLUSION: High cure rates of Hepatitis C with DAAs are achievable in clinical settings of Cameroon. However, the accessibility and provision of HCV screening, diagnosis, treatment, monitoring and care should be addressed for large-scale implementation.

OBJECTIFS: Les antiviraux à action directe (AAD) hautement efficaces pour le traitement de l'hépatite C sont largement inaccessibles en Afrique subsaharienne. Les données sur la faisabilité du traitement et les résultats en milieu clinique sont limités. Nous avons évalué la faisabilité d'atteindre un taux de guérison élevé (≥90%) avec les AAD dans six cliniques de gastro-entérologie au Cameroun. MÉTHODES: Les patients atteints d'une infection chronique par le virus de l'hépatite C (VHC) ont été traités pendant 12 ou 24 semaines avec le ledipasvir/sofosbuvir, le ledipasvir/sofosbuvir/ribavirine ou le sofosbuvir/ribavirine, selon le stade de la maladie du foie et le génotype du VHC. Le taux de guérison a été défini comme la proportion de patients présentant une réponse virologique soutenue 12 semaines après la fin du traitement (SVR12) parmi tous les patients ayant terminé le traitement. RÉSULTATS: Nous avons identifié 190 patients positifs pour l'ARN du VHC entre septembre 2017 et août 2018, dont 161 (84,7%) ont commencé le traitement. 105 (65,2%) étaient des femmes, l'âge médian était de 61,3 ans [IQR = 55,9-66,9] et 11 (6,8%) étaient positifs pour le VIH. L'ARN plasmatique médian était de 6,0 log10 UI/mL [IQR = 5,6-6,4]. Les génotypes du VHC identifiés étaient 1 (34,8%), 2 (13,7%), 4 (50,9%), 1 et 4 (0,6%); 46 (28,6%) souches provenant de 160 infections à génotype unique n'étaient pas sous-typables. Sur 158 patients ayant terminé le traitement, 152 (96,2%, IC95%: 91,9-98,6%) ont atteint la RVS12. Six patients n'ont pas atteint la RVS12: cinq portaient le VHC avec des mutations de résistance NS5A et un avec des mutations de résistance NS5B. Trois patients sont décédés avant et deux après la fin du traitement. Les événements indésirables les plus courants étaient l'asthénie (12,0%), les céphalées (11,4%) et les étourdissements (18,9%). CONCLUSION: Des taux élevés de guérison de l'hépatite C avec les AAD sont réalisables dans les milieux cliniques du Cameroun. Cependant, l'accessibilité et la fourniture du dépistage, le diagnostic, du traitement, de la surveillance et des soins du VHC devraient être adressés pour une mise en œuvre à grande échelle.

The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings.

In a Policy Forum, Peter Ehrenkranz and colleagues discuss the contribution of CD4 and viral load testing to outcomes for people with HIV in low- and middle-income countries.

Compliance with laboratory monitoring guidelines in outpatient HIV care: a qualitative study in the Netherlands.

Evidence-based guidelines in HIV care aim to improve patients' health outcomes, quality of care, and cost-effectiveness. Laboratory monitoring plays an important role in assessing clinical status of patients and forms an integral part of HIV treatment guidelines. The Dutch HIV monitoring foundation (Stichting HIV Monitoring) previously observed variation between HIV treatment centres in the Netherlands in terms of compliance with guidelines for performing laboratory tests. Drawing on qualitative research methods, this article aims to describe factors that influence guideline compliance for laboratory monitoring in outpatient HIV care in the Netherlands. Twelve semi-structured in-depth interviews were conducted with a convenience sample of physicians from four HIV treatment centres. In general, physicians perceived laboratory guidelines as useful. However, unclear online visual representation of the guidelines, a lack of set reminders for tests, and assessment of patients' risk behaviour, which differs per patient, were identified as barriers to guideline compliance. The compartmentalisation of the Dutch healthcare system was viewed as hampering guideline compliance. A clinical-decision-support tool could possibly facilitate compliance with laboratory monitoring guidelines. Moreover, better alignment of HIV outpatient care, municipal health services and primary care, in terms of laboratory testing, could optimize efficiency, increase cost-effectiveness, and improve quality of HIV care.

Clinical Evaluation of an Affordable Qualitative Viral Failure Assay for HIV Using Dried Blood Spots in Uganda.

BACKGROUND: WHO recommends regular viral load (VL) monitoring of patients on antiretroviral therapy (ART) for timely detection of virological failure, prevention of acquired HIV drug resistance (HIVDR) and avoiding unnecessary switching to second-line ART. However, the cost and complexity of routine VL testing remains prohibitive in most resource limited settings (RLS). We evaluated a simple, low-cost, qualitative viral-failure assay (VFA) on dried blood spots (DBS) in three clinical settings in Uganda. METHODS: We conducted a cross-sectional diagnostic accuracy study in three HIV/AIDS treatment centres at the Joint Clinical Research Centre in Uganda. The VFA employs semi-quantitative detection of HIV-1 RNA amplified from the LTR gene. We used paired dry blood spot (DBS) and plasma with the COBASAmpliPrep/COBASTaqMan, Roche version 2 (VLref) as the reference assay. We used the VFA at two thresholds of viral load, (>5,000 or >1,000 copies/ml). RESULTS: 496 paired VFA and VLref results were available for comparative analysis. Overall, VFA demonstrated 78.4% sensitivity, (95% CI: 69.7%-87.1%), 93% specificity (95% CI: 89.7%-96.4%), 89.3% accuracy (95% CI: 85%-92%) and an agreement kappa = 0.72 as compared to the VLref. The predictive values of positivity and negativity among patients on ART for >12 months were 72.7% and 99.3%, respectively. CONCLUSIONS: VFA allowed 89% of correct classification of VF. Only 11% of the patients were misclassified with the potential of unnecessary or late switch to second-line ART. Our findings present an opportunity to roll out simple and affordable VL monitoring for HIV-1 treatment in RLS.

Absolute CD4 T-cell counting in resource-poor settings: direct volumetric measurements versus bead-based clinical flow cytometry instruments.

Flow cytometry is an accurate but expensive method to determine absolute CD4 cell counts. We compared different methods to measure absolute CD4 counts in blood samples from HIV-infected and uninfected subjects using a research/clinical flow cytometer (FACScan); a dedicated clinical instrument (FACSCount); and a volumetric, mobile, open-system flow cytometer equipped with 3 fluorescence and 2 light scatter detectors (Cyflow SL blue). The FACScan and Cyflow were used as single-platform instruments, but they differ in running cost, which is a central factor for resource-poor settings. Direct volumetric and bead-based CD4 measurements on the Cyflow were compared with 2 bead-based single-platform CD4 measurements on the FACSCount and on FACScan (TruCount) in "Le Dantec" Hospital, Dakar, Senegal, using whole blood samples from 102 HIV+ and 28 HIV- subjects. The agreement between the various measurement methods was evaluated by Bland-Altman analysis. Volumetric CD4 measurements on the Cyflow using a no-lyse-no-wash (NLNW) procedure and a lyse-no-wash (LNW) procedure correlated well with each other (R2 = 0.98) and with CD4 measurements on the FACSCount (R2 = 0.97) and FACScan (R2 = 0.97), respectively. Red blood cell lysis had no negative effect on the accuracy of absolute CD4 counting on the Cyflow. An excellent correlation was observed between bead-based CD4 measurements on the Cyflow and CD4 measurements on the FACSCount (R2 = 0.99) and FACScan (R2 = 0.99). Rigid internal and external quality control monitoring and adequate training of technicians were considered essential to generate accurate volumetric CD4 measurements on the Cyflow.