Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy

Etiebet, Mary-Ann; Shepherd, James; Nowak, Rebecca G.; Charurat, Man; Chang, Harry; Ajayi, Samuel; Elegba, O. Y.; Ndembi, Nicaise; Abimiku, Alash’le; Carr, Jean K.; Eyzaguirre, Lindsay M.; Blattner, William A.

doi:10.1097/qad.0b013e32835b0f59

Cited by 22 publications

(26 citation statements)

References 44 publications

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“…TDF is preferred to its predecessors AZT and d4T in the ART program because of its better safety profile [37] which has been recommended by WHO for HIV first-line treatment. Researchers found that patients on TDF-based first-line regimens had fewer drug-resistant mutations [38]. With the scale-up of TDF, evidence on this issue tends to show different results concerning mortality, the CD4 cell count, and virological failure [38–40].…”

Section: Discussionmentioning

confidence: 99%

“…Researchers found that patients on TDF-based first-line regimens had fewer drug-resistant mutations [38]. With the scale-up of TDF, evidence on this issue tends to show different results concerning mortality, the CD4 cell count, and virological failure [38–40]. In our study, patients at the survey on regimens with and without TDF were 5.4% (19/355) and 3.4% (14/410), respectively (P = 0.19).…”

Section: Discussionmentioning

confidence: 99%

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Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China

et al. 2016

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BackgroundChina’s National Free Antiretroviral Treatment Program (NFATP) has substantially increased the survival rate since 2002. However, the emergence of HIV drug resistance (HIVDR) limits the durability and effectiveness of antiretroviral treatment (ART) in at risk patients.MethodA cross-sectional survey was conducted among patients having received a median of 13.9 months of ART in eight provinces in China. Demographic and clinical information was collected, and venous blood was sampled for CD4 cell counts, measurement of the HIV viral load (VL), and HIV drug resistance (HIVDR) genotyping. Possible risk factors for HIVDR were analyzed by the logistic regression model.ResultsThe study included 765 patients. Among them, 65 patients (8.5%) had virological failure (VLF) defined as ≥1,000 copies/ml. Among the individuals with VLF, 64 were successful genotyped, and of these, 33 had one or more HIVDR mutations. The prevalence of HIVDR mutations among patients receiving first-line ART was 4.3% (33/765). All of the patients with HIVDR mutations were resistant to non-nucleoside transcriptase inhibitors, 81.8% were resistant to nucleoside reverse transcriptase inhibitors, and only 3% had mutations that caused resistance to protease inhibitors. Having lower ratios of drug intake in the past month and dwelling in two southwestern provinces were factors independently associated with the emergence of HIVDR.ConclusionMost patients receiving first-line ART treatment achieved sound virological and immunological outcomes. However, poor adherence is still a key problem, which has led to the high rate of HIVDR. It was notable that the proportion of drug resistance widely varied among the provinces. More studies are needed to focus on adherence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China

et al. 2016

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“…For all children with a pre-treatment VL >1000 cps/ml, population-based sequencing of the HIV-1 pol gene was performed by the reference laboratory of the Institute of Human Virology in Abuja, Nigeria. HIV-1 RNA was extracted from 200 µL plasma, amplified and sequenced as previously described [10] at the National WHO HIV drug resistance reference laboratory of the Institute of Human Virology in Abuja, Nigeria, using an in-house method and primers designed and optimized for CFR02_AG and subtype G isolates [11]. Obtained sequences were visually inspected using Sequencher (Gene Codes Corp., Ann Arbor, MI, USA) at two independent laboratories to verify that each nucleotide base was covered at least by three reads, one of which had to be in the opposite direction of the other two.…”

Section: Methodsmentioning

confidence: 99%

“…Inclusion criteria were as follows: age 512 years, confirmed HIV-1 test (positive HIV antibody test if age !18 months, or a positive HIV nucleic acid polymerase chain reaction (PCR) test if age 518 months), eligibility for initiation of first-line ART according to national guidelines at that time (all HIVinfected children B2 years of age, CD4 count B750 cells/m 3 in children 2 to 5 years and CD4 count B350 cells/mm 3 in children !5 years) [9] and written informed consent by the parent or guardian. If the child was eight years or older and had disclosed HIV status, assent was required as well.…”

Section: Study Design and Populationmentioning

confidence: 99%

High levels of pre‐treatment HIV drug resistance and treatment failure in Nigerian children

Boerma

Boender

Sigaloff

et al. 2016

Journal of the International AIDS Society

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IntroductionPre-treatment HIV drug resistance (PDR) is an increasing problem in sub-Saharan Africa. Children are an especially vulnerable population to develop PDR given that paediatric second-line treatment options are limited. Although monitoring of PDR is important, data on the paediatric prevalence in sub-Saharan Africa and its consequences for treatment outcomes are scarce. We designed a prospective paediatric cohort study to document the prevalence of PDR and its effect on subsequent treatment failure in Nigeria, the country with the second highest number of HIV-infected children in the world.MethodsHIV-1-infected children ≤12 years, who had not been exposed to drugs for the prevention of mother-to-child transmission (PMTCT), were enrolled between 2012 and 2013, and followed up for 24 months in Lagos, Nigeria. Pre-antiretroviral treatment (ART) population-based pol genotypic testing and six-monthly viral load (VL) testing were performed. Logistic regression analysis was used to assess the effect of PDR (World Health Organization (WHO) list for transmitted drug resistance) on subsequent treatment failure (two consecutive VL measurements >1000 cps/ml or death).ResultsOf the total 82 PMTCT-naïve children, 13 (15.9%) had PDR. All 13 children harboured non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations, of whom seven also had nucleoside reverse transcriptase inhibitor resistance. After 24 months, 33% had experienced treatment failure. Treatment failure was associated with PDR and a higher log VL before treatment initiation (adjusted odds ratio (aOR) 7.53 (95%CI 1.61–35.15) and 2.85 (95%CI 1.04–7.78), respectively).DiscussionPDR was present in one out of six Nigerian children. These high numbers corroborate with recent findings in other African countries. The presence of PDR was relevant as it was the strongest predictor of first-line treatment failure.ConclusionsOur findings stress the importance of implementing fully active regimens in children living with HIV. This includes the implementation of protease inhibitor (PI)-based first-line ART, as is recommended by the WHO for all HIV-infected children <3 years of age. Overcoming practical barriers to implement PI-based regimens is essential to ensure optimal treatment for HIV-infected children in sub-Saharan Africa. In countries where individual VL or resistance testing is not possible, more attention should be given to paediatric PDR surveys.

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“…TDF is a nucleotide reverse transcriptase inhibitor that has been studied as a potential PrEP medication because it was found to be generally safe when used for HIV treatment [22, 23], achieve high concentrations in genital compartments [24, 25], and have a high genetic barrier to resistance [26, 27]. Studies with macaques have shown that it can protect against retroviral challenge when administered as PrEP [28].…”

Section: Introductionmentioning

confidence: 99%

Pre-Exposure Prophylaxis to Prevent HIV Infection: Current Status, Future Opportunities and Challenges

Krakower

Mayer

2015

Drugs

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As the global incidence of HIV exceeds 2 million new infections annually, effective interventions to decrease HIV transmission are needed. Randomized placebo-controlled studies have demonstrated that daily oral antiretroviral pre-exposure chemoprophylaxis (PrEP) with a fixed-dose combination tablet containing tenofovir disoproxil fumarate and emtricitabine can significantly reduce HIV incidence among diverse at-risk populations. In these studies, the efficacy of PrEP was correlated with levels of adherence. Official guidelines recommend provision of PrEP to persons at greatest risk of HIV acquisition, and demonstration projects suggest that high levels of uptake and adherence are possible outside of controlled studies. However, several potential barriers to implementing PrEP remain. These challenges include low awareness and utilization of PrEP by at-risk persons, uncertainty about adherence in “real-world” settings, the majority of healthcare providers being untrained in PrEP provision, limited data about potential adverse effects from long-term use of tenofovir-emtricitabine, high costs of PrEP medications, and stigma associated with PrEP use and the behaviors that would warrant PrEP. Innovative pharmacologic chemoprophylactic approaches could provide solutions to some of these challenges. Less-than-daily oral dosing regimens and long-acting injectable medications could reduce pill burdens and facilitate adherence, and local delivery of PrEP medications to genital compartments via gels, rings and films may limit systemic drug exposure and potential toxicities. As the portfolio of chemoprophylactic agents and delivery systems expands to meet the diverse sexual health needs and product preferences of individuals who may benefit from PrEP, it is hoped that antiretroviral chemoprophylaxis could become an acceptable, feasible, and highly effective addition to existing HIV prevention strategies.

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Tenofovir-based regimens associated with less drug resistance in HIV-1-infected Nigerians failing first-line antiretroviral therapy

Cited by 22 publications

References 44 publications

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China

Drug Resistance and Virological Failure among HIV-Infected Patients after a Decade of Antiretroviral Treatment Expansion in Eight Provinces of China

High levels of pre‐treatment HIV drug resistance and treatment failure in Nigerian children

Pre-Exposure Prophylaxis to Prevent HIV Infection: Current Status, Future Opportunities and Challenges

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