High turnaround times and low viral resuppression rates after reinforced adherence counselling following a confirmed virological failure diagnostic algorithm in HIV-infected patients on first-line antiretroviral therapy from Tanzania.

OBJECTIVE: Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale-up of HIV-RNA monitoring in Africa and timely switch to second-line regimens are challenged. METHODS: A WHO adapted confirmed virological treatment screening algorithm (HIV-RNA screening, enhanced adherence counselling, confirmatory HIV-RNA testing) was evaluated in HIV-infected patients on first-line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second-line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance. RESULTS: HIV-RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time-on-treatment 6.3 years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30 years (RR 5.2 [95% CI: 2.5-10.8]), years on ART ≥3 years (RR 3.0 [1.0-8.9]), CD4-counts <200 cells/µl (RR 9.3 [4.0-21.8]) and poor self-reported treatment adherence (RR 2.0 [1.2-3.4]). Resuppression of HIV-RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3 months was performed in only 46.6% and switch to second-line ART within 6 months in 60.4% of patients. Major NNRTI-mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine-analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients. CONCLUSION: We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second-line treatment which could be improved using novel point-of-care viral load monitoring systems.

OBJECTIF: L'identification précoce de l'échec virologique confirmé est primordiale pour éviter l'accumulation de résistance aux médicaments chez les patients sous traitement antirétroviral (ART). L'intensification du suivi de l'ARN du VIH en Afrique et le passage en temps opportun aux schémas thérapeutiques de deuxième intention sont adressés. MÉTHODES: Nous avons évalué un algorithme adapté de l'OMS confirmé pour le dépistage du traitement virologique (dépistage de l'ARN du VIH, adhésion renforcée du conseil, test de confirmation de l'ARN du VIH) chez des patients infectés par le VIH sous ART de première intention en Tanzanie. Les critères principaux comprenaient la répression virale et les taux d'échec virologique, la rétention et et la durée de rotation de l'algorithme de dépistage jusqu'à l'initiation de l'ART de deuxième ligne. Les critères d'évaluation secondaires comprenaient les facteurs de risque d'échec du traitement virologique et les profils de résistance génotypique aux médicaments. RÉSULTATS: Un ARN-VIH >1000 copies/ml au premier dépistage a été détecté chez 58/356 (16,3%) patients (durée médiane de traitement de 6,3 ans, 25% d'échec immunologique du traitement). Les facteurs de risque ajustés pour l'échec virologique étaient l'âge <30 ans (RR: 5,2 [IC95%: 2,5-10,8]), les années sous ART ≥3 ans (RR: 3,0 [1,0-8,9]), la numération des CD4 <200 cellules/µL (RR: 9,3 [4,0-21,8]) et une mauvaise compliance au traitement autodéclarée (RR: 2,0 [1,2-3,4]). Une re-suppression du VIH-ARN <1000 copies/mL a été observée chez 5/50 (10%) des cas après renforcement du conseil pour la compliance. Un test de confirmation dans les 3 mois n'a été réalisé que dans 46,6% des cas et le passage à l'ART de deuxième ligne dans les 6 mois chez 60,4% des patients. Des mutations NNRTI majeures ont été détectées chez tous les 30 patients, des mutations NRTI chez 96,7% et ≥3 mutations analogues à la thymidine chez 40%. Aucune option NRTI restante n'a été prévue chez 57% des cas et une sensibilité limitée chez 23% des patients. CONCLUSION: Nous avons observé de faibles taux de re-suppression virale après des conseils d'adhésion, associés à des taux élevés de résistance accumulée aux médicaments. La charge élevée des visites et les délais de rotation pour le diagnostic confirmé d'échec virologique ont retardé le passage au traitement de deuxième intention, ce qui pourrait être amélioré à l'aide de nouveaux systèmes de surveillance de la charge virale au point des soins.

Evaluation of Antimicrobial Utilization and Concordance with National Guidelines at a Tertiary Hospital in the Southern Highlands Zone of Tanzania.

Antimicrobial resistance is a growing concern in sub-Saharan Africa, and antimicrobial stewardship (AMS) programs have not been widely implemented in this region. We evaluated antibiotic prescribing patterns and concordance with national guidelines at Mbeya Zonal Referral Hospital (MZRH) in Tanzania. Adult inpatient medical records were chronologically reviewed from January 1, 2018 until 100 records documenting antibiotic therapy were evaluated. The primary endpoint was concordance with national guidelines for indication-based antibiotic selection and duration. Data were summarized using descriptive statistics. Overall, 155 records with sufficient data were reviewed. The 100 records which involved antibiotic therapy represented 171 unique antibiotic courses. The most common indication for antibiotics was bacterial pneumonia. Ceftriaxone and metronidazole, the most commonly used antibiotics, were administered in 40% and 24% of courses, respectively. Indication-based antibiotic selection was concordant with national guidelines in 63% of courses, but this fell to 15% when course duration was taken into account. Antibiotic courses were completed as prescribed 28% of the time among evaluable courses. A microbiologic culture of any kind was obtained in 17% of patients. In conclusion, antibiotic therapy was often incomplete, was generally guideline discordant, exhibited limited diversity of selection, and frequently lacked diagnostic confirmation. These data, combined with local susceptibility patterns, may be used to foster AMS efforts for improved compliance with guidelines at MZRH in the future.

Integrating Local, National, and International Stakeholders in Outbreak Preparedness in Developing Countries: Conclusions from a Conference in Mbeya, Tanzania.

A conference called "Outbreaks in Tanzania-Are We Prepared?" was held in Mbeya, Tanzania, on September 14 and 15, 2015, accompanied by a training workshop on infection prevention and control for local stakeholders from September 16 to 18, 2015. The objective of the conference was to revisit past disease epidemics and to reflect on the current status of surveillance and outbreak preparedness in Tanzania, including an overview of agents relevant to biosecurity. The conference brought together national authorities of Tanzania, regional public health representatives, people from research and academic institutions, and international stakeholders. Key findings of the event were: (1) although national frameworks for surveillance and preparedness exist, their implementation presents challenges, and local health structures need support in implementation; (2) the ability to identify and properly manage infectious diseases of public health concern is crucial in empowering the local health workforce to contribute to surveillance measures, which in turn allows for realistic risk assessments and management algorithms; and (3) in settings of limited resources, research activities acquire an additional responsibility toward national surveillance and capacity building and should be integrated into national epidemic preparedness plans. This event was the first of its kind in Tanzania, facilitating direct discussion among regional, zonal, national, and international stakeholders on surveillance and outbreak preparedness. The conference's conclusions are relevant to strengthening health systems in other low- and middle-income countries.