Emerging integrase strand transfer inhibitor drug resistance mutations among children and adults on ART in Tanzania: findings from a national representative HIV drug resistance survey.

BACKGROUND: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients. OBJECTIVES: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania. METHODS: A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation. RESULTS: HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs. CONCLUSIONS: More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

Extent and Resistance Patterns of ESKAPE Pathogens Isolated in Pus Swabs from Hospitalized Patients.

Antimicrobial resistance has persisted as a global threat with increasing associated numbers of morbidity and mortality. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) were termed by the Infectious Diseases Society of America as a group of bacteria with rapid antibiotic resistance development. The aim of the study was to describe the extent and resistance patterns of ESKAPE pathogens isolated in pus swabs from patients admitted at Muhimbili National Hospital, Tanzania. A retrospective cross-sectional study was performed in August 2019. A total of 75 admitted patients with open wounds and surgical site infections were recruited. Files were analyzed to collect microbiology laboratory data and relevant patient data. A total of 76 clinically significant bacteria were isolated of which 52 bacteria were categorized as ESKAPE pathogens. The most common bacteria isolated were 25% (n = 19/76) P. aeruginosa and 17.1% S. aureus. A high level of antibiotic resistance was shown in all ESKAPE and non-ESKAPE pathogens. The Gram-negative bacteria of ESKAPE pathogens were further analyzed comparing 3rd generation cephalosporin and carbapenems resistance patterns. A. baumannii showed the highest resistance towards 3rd generation cephalosporin and carbapenems. In addition, P. aeruginosa showed high resistance to 3rd generation cephalosporins with 89.5% resistance, with E. coli showing high resistance to carbapenems with 50.0% resistance. The burden of ESKAPE pathogens is high in pus swabs obtained from admitted patients at Muhimbili National Hospital. The results showed high antibiotic resistance within ESKAPE and non-ESKAPE pathogens including the "last resort" antibiotics: 3rd generation cephalosporin and carbapenems.

HIV viral suppression in the era of dolutegravir use: Findings from a national survey in Tanzania.

BACKGROUND: Tanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen. Eighteen months later we investigated the HIV viral suppression rates and the factors associated with lack of viral suppression among PLHIV (children and adults) in Tanzania. METHODOLOGY: A cross-sectional survey was conducted from September to December 2020 among PLHIV on antiretroviral therapy (ART) in Tanzania. Whole blood samples, demographic data and clinical information were obtained from eligible adults (≥15 years) and children (< 15 years) attending thirty-six HIV care and treatment centres located in 22 regions of Tanzania mainland. A whole blood sample from each participant was processed into plasma and HIV viral load was estimated using real-time PCR. HIV viral suppression was defined at a cut-off of < 50 copies/mL as recommended by WHO. Analyses were conducted using descriptive statistics to establish the national representative prevalence of viral suppression, and logistic regression analyses to determine independent factors associated with non-suppression. RESULTS: A total of 2,039 PLHIV on ART were recruited; of these, adults and children were 57.5% (n = 1173) and 42.5% (n = 866), respectively. Among the adult population, the mean age and standard deviation (SD) was 42.1 ± 12.4 years, with 64.7% being female. Among children, the mean age and SD were 9.6 ± 3 years, and 53.2% were female. Overall viral suppression at < 50 copies/mL (undetectable) was achieved in 87.8% of adults and 74.4% of children. Adults and children on dolutegravir-based regimen recorded viral suppression rates of 89.7% and 85.1% respectively. Factors independently associated with lack of viral suppression status in the adult population were age and ART adherence while in the children population, the factors were sex, ART adherence, and current ART regimen (p<0.05). CONCLUSION: Dolutegravir-based regimens are promising to help attain epidemic control in Tanzania. More efforts especially on ART adherence are needed to attain optimal treatment outcomes for children and adults PLHIV in Tanzania.