High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo
TL;DR: The high number of resistant strains observed in Togo shows clearly that the emergence of HIV drug resistance is of increasing concern in countries where ART is now widely used, and can compromise the long-term success of first- and second-line ART.
Abstract: With widespread use of antiretroviral (ARV) drugs in Africa, one of the major potential challenges is the risk of emergence of ARV drug-resistant HIV strains. Our objective is to evaluate the virological failure and genotypic drug-resistance mutations in patients receiving first-line highly active antiretroviral therapy (HAART) in routine clinics that use the World Health Organization public health approach to monitor antiretroviral treatment (ART) in Togo.
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Dissertation•
01 Mar 2013
TL;DR: This thesis is submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy of the University of Wolverhampton.
Abstract: This thesis is submitted in partial fulfilment of the requirements for the award of the degree of Doctor of Philosophy (PhD) of the University of Wolverhampton
6 citations
Cites background from "High prevalence of HIV-1 drug resis..."
...For ART to be effective, high levels of patient adherence are needed since poor adherence is also associated with the development of drug resistance [48,50]....
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TL;DR: Long-term antiretroviral therapy remains effective for treatment of HIV/AIDS, resulting in higher mean body weight, effective viral inhibition and a higher CD4 count and a positive correlation between immunological effectiveness and viral inhibition.
Abstract: The aim of this study was to evaluate the long-term effectiveness of first-line antiretroviral therapy in HIV/AIDS patients in Southeast China. A total of 450 eligible patients were selected to initiate first-line antiretroviral therapy from February 2005 through August 2009. During the study period from 2009 through 2013, each subject received clinical and laboratory monitoring for effectiveness, safety and toxicity once every 3 months in the first year, and once every 6 months in the following years. The response to first-line antiretroviral therapy was evaluated through body weight gain and immunological and virological outcomes. During the mean follow-up period of 70.86 ± 28.9 months, the overall mortality was 14.2%. The mean body weight and CD4(+) counts increased significantly following antiretroviral therapy as compared to baselines across the follow-up period, and the rate of immunological effectiveness was over 85% in all subjects at 2 to 5 years of treatment. The rate of inhibition of HIV virus was 87.67%, 89.32%, 91.73%, 92.8% and 91.63% across the study period. In addition, significant differences were detected after treatment as compared to baselines, and Pearson correlation analysis revealed a positive correlation between immunological effectiveness and viral inhibition. Forty-eight percent of the subjects changed antiretroviral drugs once, and 16.22% twice, and 31 patients switched from first-line to second-line antiretroviral therapy. Long-term antiretroviral therapy remains effective for treatment of HIV/AIDS, resulting in higher mean body weight, effective viral inhibition and a higher CD4 count. Immunological effectiveness of antiretroviral therapy positively correlates with HIV viral inhibition.
6 citations
TL;DR: Reconstruction of the demographic history of the GCV-PT clade circulating in Cape Verde and Portugal indicates that this viral clade displayed an initial phase of exponential growth during the 1980s and 1990s, followed by a decline in growth rate since the early 2000s.
Abstract: The human immunodeficiency virus type 1 (HIV-1) subtype G is the most prevalent and second most prevalent HIV-1 clade in Cape Verde and Portugal, respectively; but there is no information about the origin and spatiotemporal dispersal pattern of this HIV-1 clade circulating in those countries. To this end, we used Maximum Likelihood and Bayesian coalescent-based methods to analyze a collection of 578 HIV-1 subtype G pol sequences sampled throughout Portugal, Cape Verde and 11 other countries from West and Central Africa over a period of 22 years (1992 to 2013). Our analyses indicate that most subtype G sequences from Cape Verde (80%) and Portugal (95%) branched together in a distinct monophyletic cluster (here called GCV-PT). The GCV-PT clade probably emerged after a single migration of the virus out of Central Africa into Cape Verde between the late 1970s and the middle 1980s, followed by a rapid dissemination to Portugal a couple of years later. Reconstruction of the demographic history of the GCV-PT clade circulating in Cape Verde and Portugal indicates that this viral clade displayed an initial phase of exponential growth during the 1980s and 1990s, followed by a decline in growth rate since the early 2000s. Our data also indicate that during the exponential growth phase the GCV-PT clade recombined with a preexisting subtype B viral strain circulating in Portugal, originating the CRF14_BG clade that was later disseminated to Spain and Cape Verde. Historical and recent human population movements between Angola, Cape Verde and Portugal probably played a key role in the origin and dispersal of the GCV-PT and CRF14_BG clades.
4 citations
Cites background from "High prevalence of HIV-1 drug resis..."
...GH/TG: Ghana/Togo....
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...This subtype reaches the highest prevalence in some African countries, comprising 30–50% of HIV-1 infections in Cape Verde [3,4] and Nigeria [5–12], and 5–15% of HIV-1 infections in Angola [13–15], Benin [16], Niger [17,18] and Togo [19,20]....
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...%) and Benin (47%); 3) the GWA-II clade predominates in Togo/Ghana (84%); and 4) the GCV-PT clade was the dominant lineage in Cape Verde (80...
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...The major subtype G clades detected in our previous study in West Africa were the GWA-I (that most probably emerged in Nigeria around the middle 1970s) and the GWA-II (that most probably emerged in Togo or Ghana around the late 1970s) [21]....
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...Los Alamos classification Region Country N Sampling interval Subtype G West Africa Benin 15 2004–2009 Ghana 9 2002–2010 Cape Verde 60 2005–2011 Nigeria 223 1992–2013 Senegal 12 1998–2010 Togo 28 2006–2011 West Central Africa Cameroon 62 1997–2012 Gabon 6 2000–2008 Equatorial Guinea 4 2005–2009 Central Africa Angola 20 1997–2010 DRC 12 1993–2007 Republic of Congo 8 2003 Europe Portugal 107 1998–2008 CRF14_BG Europe Portugal 2a 1998–2008 Spain 10a 1999–2005 a Subtype G pol fragments recovered from full-length CRF14_BG reference sequences. doi:10.1371/journal.pone.0127384.t001 PLOS ONE | DOI:10.1371/journal.pone.0127384 May 20, 2015 3 / 16 molecular clock model and a uniform prior on clock rate (1.5–3.0 x 10–3 subst/site/year) [42]....
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TL;DR: In this article, the authors assessed viral load suppression and acquired drug resistance, as well as future efficacy of dolutegravir-based combinations for patients living in semi-rural regions of Gabon.
Abstract: BACKGROUND The projected UNAIDS goal of ending AIDS by 2030 requires significant global efforts to improve current and future ART strategies. In this study, we assessed viral load (VL) suppression and acquired drug resistance, as well as future efficacy of dolutegravir-based combinations for patients living in semi-rural regions of Gabon. METHODS Eligible study participants were adults receiving ART and recruited between 2018 and 2019 in Franceville, Gabon. VL testing was conducted to assess VL suppression and HIV drug resistance (HIVDR) testing was performed to identify resistance mutations and assess their impact on ongoing and future ART regimens. RESULTS We recruited 219 participants overall. The median time on ART was 27 months and 216/219 participants were on first-line ART. VL suppression (VL < 1000 copies/mL) was 57.1% (95% CI 50.5-63.8) overall; 59.4% (51.4-67.5) and 52.2% (40.3-64.2) for women and men, respectively. The overall prevalence of HIVDR was 21.9% among the study population and 67.2% among those who failed ART. Presence of both NRTI and NNRTI mutations was found in 84.6% of sequences with drug resistance mutations, and full activity of a dolutegravir-based first-line regimen including tenofovir disoproxil fumarate/lamivudine/dolutegravir was expected only for 5/39 patients with a resistant virus. CONCLUSIONS This study shows a very low rate of VL suppression in a semi-rural context in Africa. Moreover, the high burden of HIVDR has affected both current and newly recommended ART strategies. Better management of ART in resource-limited settings is still a challenging ambition.
4 citations
TL;DR: A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL’> 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.
Abstract: OBJECTIVES
To assess whether a single instance of low-level viraemia (LLV) is associated with the presence of drug resistance mutations (DRMs) and predicts subsequent virological failure (VF) in adults receiving ART in 30 communities participating in the Botswana Combination Prevention Project.
METHODS
A total of 6078 HIV-1 C pol sequences were generated and analysed using the Stanford HIV drug resistance database. LLV was defined as plasma VL = 51-999 copies/mL and VF was defined as plasma VL ≥ 1000 copies/mL.
RESULTS
Among 6078 people with HIV (PWH), 4443 (73%) were on ART for at least 6 months. Of the 332 persons on ART with VL > 50 copies/mL, 175 (4%) had VL ≥ 1000 copies/mL and 157 (4%) had LLV at baseline. The prevalence of any DRM was 57 (36%) and 78 (45%) in persons with LLV and VL ≥ 1000 copies/mL, respectively. Major DRMs were found in 31 (20%) with LLV and 53 (30%) with VL ≥ 1000 copies/mL (P = 0.04). Among the 135 PWH with at least one DRM, 17% had NRTI-, 35% NNRTI-, 6% PI- and 3% INSTI-associated mutations. Among the 3596 participants who were followed up, 1709 (48%) were on ART for ≥6 months at entry and had at least one subsequent VL measurement (median 29 months), 43 (3%) of whom had LLV. The OR of experiencing VF in persons with LLV at entry was 36-fold higher than in the virally suppressed group.
CONCLUSIONS
A single LLV measurement while on ART strongly predicted the risk of future VF, suggesting the use of VL > 50 copies/mL as an indication for more intensive adherence support with more frequent VL monitoring.
4 citations
References
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01 Jan 2006
TL;DR: These guidelines are primarily intended for use by national and regional HIV programme managers managers of nongovernmental organizations delivering HIV care services and other policy-makers who are involved in the scaling up of comprehensive HIV care and ART in resource-limited countries.
Abstract: This publication is intended to serve as a reference tool for countries with limited resources as they develop or revise national guidelines for the use of ART in adults and postpubertal adolescents (see Annex 9 for pubertal Tanner staging; prepubertal adolescents should follow the WHO paediatric guidelines). The material presented takes updated evidence into account including new ART treatment options and draws on the experience of established ART scale-up programmes. The simplified approach with evidence-based standards continues to be the basis of WHO recommendations for the initiation and monitoring of ART. The guidelines are primarily intended for use by national and regional HIV programme managers managers of nongovernmental organizations delivering HIV care services and other policy-makers who are involved in the scaling up of comprehensive HIV care and ART in resource-limited countries. The comprehensive up-to-date technical and clinical information on the use of ART however also makes these guidelines useful for clinicians in resource-limited settings. The recommendations contained in these guidelines are made on the basis of different levels of evidence from randomized clinical trials high-quality scientific studies observational cohort data and where insufficient evidence is available expert opinion. The strengths of the recommendations in Table 1 are intended to indicate the degrees to which the recommendations should be considered by regional and country programmes. Cost-effectiveness is not explicitly considered as part of the recommendations although the realities of human resources health system infrastructures and socioeconomic issues should be taken into account when the recommendations are being adapted to regional and country programmes. (excerpt)
1,454 citations
TL;DR: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries, and timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART might reduce this excess mortality.
1,143 citations
TL;DR: A public-health approach to antiretroviral therapy (ART) to enable scaling-up access to treatment for HIV-positive people in developing countries, recognising that the western model of specialist physician management and advanced laboratory monitoring is not feasible in resource-poor settings.
674 citations
"High prevalence of HIV-1 drug resis..." refers methods in this paper
...In order to allow a rapid roll out of ART, countries use the World Health Organization (WHO) public health approach, which proposes standard firstline therapy, together with treatment initiation and switch guided by clinical disease progression and, where possible, with monitoring of CD4 cell counts [1]....
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TL;DR: ART treatment programs in resource-poor settings have efficacy rates similar to those reported for developed countries, and the provision of medications free of charge to the patient is associated with a significantly increased probability of virologic suppression at months 6 and 12 of ART.
Abstract: Despite the advent of effective combination antiretroviral drug therapy (ART) for the treatment of human immunodeficiency virus (HIV) infection many doubt the feasibility of ART treatment programs in resource-poor settings. We performed a meta-analysis of the efficacy of ART programs in the developing world. We searched the Medline database with the index terms “HIV” “antiretroviral therapy” “CD4 count” “viral load” “experience” and “outcomes.” A total of 201 abstracts were reviewed and 25 articles were selected for detailed review. Ten observational studies with details on patient outcomes were ultimately included in the analysis. Three readers independently extracted data from the articles. The details recorded included patient demographic characteristics baseline CD4 cell counts baseline HIV RNA viral loads ART histories outcomes and timing of the outcome measure. The proportion of subjects with an undetectable HIV viral load provided the measure of treatment efficacy. A random-effects model weighted the proportion of patients with undetectable viral load at various time points during ART. The proportion was 0.697 (95% CI 0.582–0.812) at month 6 and 0.573 (95% CI 0.432– 0.715) at month 12 of ART. The provision of medications free of charge to the patient was associated with a 29%– 31% higher probability of having an undetectable viral load at months 6 and 12 than was the requirement that patients pay part or all of the cost of therapy. ART treatment programs in resource-poor settings have efficacy rates similar to those reported for developed countries. The provision of medications free of charge to the patient is associated with a significantly increased probability of virologic suppression at months 6 and 12 of ART. (authors)
343 citations
"High prevalence of HIV-1 drug resis..." refers result in this paper
...Several cohort studies, using virological monitoring, have shown that ART treatment in resource-poor settings has efficacy rates similar to those reported for developed countries [7-12]....
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TL;DR: Reports from resource-limited countries suggest that initial ART programmes are as effective as in resource-rich countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up.
Abstract: Darunavir (TMC114) is a new HIV protease inhibitor that has demonstrated substantial antiretroviral activity against wild-type HIV-1 virus and multidrug-resistant strains Darunavir inhibits and is primarily metabolized by cytochrome P450 3A (CYP3A) isoenzymes and is coadministered with low-dose ritonavir (darunavir/r); ritonavir is an inhibitor of CYP3A isoenzymes and pharmacologically enhances darunavir, resulting in increased plasma concentrations and allowing for a lower daily dose The t1/2 (terminal elimination half-life) of darunavir is 15 h in the presence of ritonavir An extensive darunavir/r drug-drug interaction programme has been undertaken, covering a wide range of therapeutic areas Studies conducted in HIV-negative healthy volunteers and in HIV-infected patients show that the potential for interactions is well characterized and the interactions are manageable For most drugs investigated, no dose adjustments of darunavir/r or the co-administered drug are required This article reviews all the pharmacokinetic and drug-drug interaction studies conducted to date for darunavir/r, providing guidance on how to co-administer darunavir/r with many other antiretroviral or non-antiretroviral medications commonly used in HIV-infected individuals
305 citations
"High prevalence of HIV-1 drug resis..." refers background in this paper
...Since individual patient monitoring for viral load and drug resistance is not yet possible, the system that WHO (HIVRESNET) has established for the surveillance of transmitted drug resistance and the monitoring of ART resistance at sentinel sites should be implemented in order to inform health authorities on the efficiency of first- and second-line ART and allow recommendations on future ART strategies [ 17 ]....
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