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Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

ABSTRACT: Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilities with HIV-care and treatment clinics from October, 2017 to August, 2018. Cases and controls were HIV-infected individuals with VF and viral suppression (VS) respectively. HIV-1 reverse transcriptase and protease genes were amplified and sequenced. Stanford University's HIV drug resistance database and REGA subtyping tool 3.0 determined HIVDRM and HIV-1 subtypes respectively. Odds ratios (OR) with 95% confidence interval (95% CI) investigated predictors of VF. P-value < 5% was considered statistically significant. A total of 124 participants were recruited, of whom 63 (50.8%) had VF, 61 (49.2%) had VS and 82 (66.1%) were females. Median [IQR] age and duration on ART were 45 [35-52] years and 72 [48-104] months respectively. Twenty-five out of 26 selected samples from cases were successfully sequenced. Twenty-four samples (96%) had at least one major mutation conferring resistance to HIV drugs, with non-nucleoside analogue reverse transcriptase inhibitor (NNRTI)-resistance associated mutations as the majority (92%). Frequent NNRTI-resistance associated mutations were K103N (n = 11), V106M (n = 5) and G190A (n = 5). Prevalent nucleoside analogue reverse transcriptase inhibitors-resistance associated mutations were M184V (n = 17), K70R (n = 7) and D67N (n = 6). Dual-class resistance was observed in 16 (64%) samples. Thirteen samples (52%) had at least one thymidine analogue-resistance associated mutation (TAM). Three samples (12%) had T69D mutation with at least 1 TAM. Two samples (8%) had at least one mutation associated with protease inhibitor resistance. Age [aOR = 0.94, 95% CI (0.90-0.97), p < 0.001] and occupation [aOR = 0.35, 95% CI (0.12-1.04), p = 0.059] associated with VF. In conclusion, HIV drug resistance is common among people failing antiretroviral therapy. Resistance testing will help to guide switching of HIV drugs.

SUBMITTER: Mziray SR

PROVIDER: S-EPMC7521739 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

Mziray Shabani Ramadhani SR Kumburu Happiness H HH Assey Hellen B HB Sonda Tolbert B TB Mahande Michael J MJ Msuya Sia E SE Kiwelu Ireen E IE

PloS one 20200928 9

Emergence of HIV drug resistance poses a serious risk of inactivity to all currently approved antiretroviral drugs. Profiles of HIV drug resistance mutations (HIVDRM) and virological failure (VF) are not extensively studied in Tanzania. This study aimed to determine HIVDRM and predictors of VF in HIV-infected individuals failing first-line HIV drugs in Moshi, Northern Tanzania. A case-control study was conducted at Kilimanjaro Christian Medical Centre, Mawenzi, Pasua and Majengo health facilitie ...[more]

PMID: 32986709

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Project description:BackgroundWhile factors that drive early mortality among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in sub-Saharan Africa (SSA) have been described, less is known about the predictors of long-term mortality for those with ART experience.MethodsPLWH and on ART attending two HIV treatment clinics in Moshi, Tanzania were enrolled from 2008 through 2009 and followed for 3.5 years. Demographic, psychosocial, and clinical information were collected at enrollment. Plasma HIV RNA measurements were collected annually. Cause of death was adjudicated by two independent reviewers based on verbal autopsy information and medical records. Bivariable and multivariable analyses were conducted using Cox proportional hazard models to identify predictors of mortality.ResultsThe analysis included 403 participants. The median (IQR) age in years was 42 (36-48) and 277 (68.7%) participants were female. The proportion of participants virologically suppressed during the 4 collection time points was 88.5%, 94.7%, 91.5%, and 94.5%. During follow-up, 24 participants died; the overall mortality rate was 1.8 deaths per 100 person-years. Of the deaths, 14 (58.3%) were suspected to be HIV/AIDS related. Predictors of mortality (adjusted hazard ratio, 95% confidence interval) were male sex (2.63, 1.01-6.83), secondary or higher education (7.70, 3.02-19.60), receiving care at the regional referral hospital in comparison to the larger zonal referral hospital (6.33, 1.93-20.76), and moderate to severe depression symptoms (6.35, 1.69-23.87).ConclusionsAs ART coverage continues to expand in SSA, HIV programs should recognize the need for interventions to promote HIV care engagement for men and the integration of mental health screening and treatment with HIV care. Facility-level barriers may contribute to challenges faced by PLWH as they progress through the HIV care continuum, and further understanding of these barriers is needed. The association of higher educational attainment with mortality merits further investigation.

Project description:BackgroundPoor knowledge concerning appropriate antibiotic use significantly influences the misuse of antibiotics within the community, especially in developing countries where there are weaker health systems to regulate antibiotic dispensing. Antibiotic misuse leads to antibiotic resistance. This study assessed knowledge of appropriate antibiotic use among buyers in the Moshi municipality, Northern Tanzania.MethodsWe conducted a cross-sectional study in Moshi municipality between April and May 2017. Adults who bought antibiotics at drug outlets were invited to participate in the study. An exit interview was conducted with participants to collect their demographics and assess their knowledge concerning appropriate use of antibiotics. A logistic regression model was performed to determine factors associated with correct knowledge concerning antibiotic use.ResultsA total of 152 adults with a median age of 30.5 (IQR 25-42) years, were enrolled in the study. Slightly over half (n = 89, 58.6%), responded that they should stop antibiotics after finishing the dose as directed. Half (n = 77, 50.7%) thought that it was acceptable to share antibiotics with other individuals and over half of respondents (n = 95, 65.1%) thought that they should request the same antibiotics if they had used them to treat a similar illness in the past. Only 38 (25%) had adequate knowledge about the use of antibiotics. Sore throat and flu were respectively identified by 62.5% and 46.1% of respondents as conditions that can be treated with antibiotics. Higher levels of education (aOR = 4.11 95%CI = 1.44-11.71) and having health insurance (aOR = 9.05 95%CI = 3.35-24.45) were associated with better levels of knowledge concerning antibiotic use in various illnesses.ConclusionThere is inadequate knowledge concerning the indications for antibiotics and their appropriate usage. Health promotion campaigns are needed to educate the population about appropriate antibiotic use and reduce their irrational use.

Project description:IntroductionScale up of anti-retroviral therapy has enabled millions of children infected with HIV to survive into adulthood, requiring transition of care to the adult HIV clinic. This transition period is often met with anxiety and reluctance. Youth who fail to transition may create strain on capacity in the pediatric and adolescent clinics or result in individuals dropping out of care entirely. This study examined challenges and facilitators to the transition among young adults living with HIV in Moshi, Tanzania.MethodsFrom April to June 2017, in-depth interviews were conducted with young adults aged 18 to 27 years living with HIV in order to capture the spectrum of experiences from pre-transitioning youth to those who successfully transitioned to adult care. Young adults were purposively recruited based on prior study enrollees and recommendations from healthcare staff. Recruitment occurred in the adolescent, adult HIV and the prevention of mother to child transition clinics at Kilimanjaro Christian Medical Centre. Two separate in-depth interviews were conducted with eligible participants. Medical records were reviewed retrospectively to collect information on HIV-related outcomes.ResultsIn-depth interviews were held with 19 young adults. Participants mean age was 23.8 years (interquartile range 22.2 to 26.3 years); 53% were female. Most (78.9%) participants had been receiving anti-retroviral therapy for nearly a decade and 72.2% were virologically suppressed (HIV RNA <200 copies/mL). Barriers to transition included fear of losing peer networks formed in the adolescent clinic, the abrupt manner in which young adults were asked to transition, stigma, financial constraints and a lower quality of care in the adult clinic. Facilitators of transition included family and social support, positive perspectives on living with HIV and maintenance of good health. Recommendations for transition included transition preparation, transition as a group and adoption of desirable aspects of the adolescent clinic (peer networks and education) in the adult clinic.ConclusionsTransition is a complex process influenced by many factors. As the number of young adults living with HIV continues to grow, it is vital to develop a transition protocol that addresses these challenges and is feasible to implement in low-resource settings.

Dataset Information

Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

Publications

Patterns of acquired HIV-1 drug resistance mutations and predictors of virological failure in Moshi, Northern Tanzania.

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