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Journal ArticleDOI

High prevalence of HIV-1 drug resistance among patients on first-line antiretroviral treatment in Lomé, Togo

10 Jun 2011-Journal of the International AIDS Society (BioMed Central)-Vol. 14, Iss: 1, pp 30-30

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.

AbstractWith 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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Citations
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Journal ArticleDOI
TL;DR: The emergence of drug resistance following access to ART in resource-limited settings resembles what was seen inresource-rich countries and highlights the need for virological monitoring for drug failure, drug resistance testing and alternative drug regimens that have proven beneficial in these resource-rich settings.
Abstract: BackgroundThe increasing availability of antiretroviral therapy (ART) has improved survival and quality of life for many infected with HIV, but can also engender drug resistance. This review summar...

116 citations


Journal ArticleDOI
TL;DR: The findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.
Abstract: Background The limited access to virological monitoring in developing countries is a major weakness of the current antiretroviral treatment (ART) strategy in these settings. We conducted a large cross-sectional study in Burkina Faso, Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess virological failure and drug resistance mutations (DRMs) after 12 or 24 months of ART. Methods Between 2009 and 2011, we recruited adults attending ART centers 10-14 months (the M12 group) or 22-26 months (M24 group) after initiating ART. Demographic and clinical data were collected on site, and viral load was measured. Samples with a viral load of ≥ 1000 copies/mL, considered as the failure threshold, were genotyped for drug resistance assessment. Results Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages varied from 32 to 42 years. Median CD4(+) T-cell counts at ART initiation were low (99-172 cells/µL). The main ART regimens included stavudine/zidovudine plus lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was 11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these patients, respectively, had drug-resistant virus. Across sites, virological failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24 patients. Predominant DRMs were associated with ART regimens, but virus in several patients accumulated DRMs to drugs not received, such as abacavir, didanosine, tenofovir, etravirine, and rilpivirine. Conclusions Our findings show heterogeneous virological failure and illustrate that, in addition to routine access to viral load, good management of ART programs is even more critical to improve treatment outcomes in resource-limited countries.

85 citations


Journal ArticleDOI
TL;DR: The genetic diversity of HIV-1 continues to increase overtime due to demographic factors such as travel and migration and frequent co/superinfections, which leads to an increasing number of drug-resistant strains, especially in resource limited countries.
Abstract: HIV-1 in humans resulted from at least four cross-species transmissions of simian immunodeficiency viruses (SIVs) from chimpanzees and gorillas in West Central Africa, while HIV-2 viruses resulted from at least eight independent transmissions of SIVs infecting sooty mangabeys in West Africa only, where one of these transmissions (HIV-1 group M) is responsible for the global epidemic. HIV-1 M is subdivided into nine subtypes and a wide diversity of circulating recombinant forms (CRFs) and unique recombinant forms. The heterogenic HIV-1 M subtype/CRF distribution is the result of founder effects. The genetic diversity of HIV-1 continues to increase overtime due to demographic factors such as travel and migration and frequent co/superinfections. In addition, the expanded access to antiretrovirals leads to an increasing number of drug-resistant strains, especially in resource limited countries.

50 citations


Journal ArticleDOI
TL;DR: As antiretroviral treatment (ART) continues to expand in resource‐limited countries, the emergence of HIV drug resistance mutations (DRMs) is challenging in these settings.
Abstract: Introduction: As antiretroviral treatment (ART) continues to expand in resource-limited countries, the emergence of HIV drug resistance mutations (DRMs) is challenging in these settings. In Gabon (central Africa), no study has yet reported the virological effectiveness of initial ART given through routine HIV care. Methods: Following the World Health Organization (WHO) recommendations, a cross-sectional study with a one-time HIV-1 RNA viral load (VL) measurement was conducted in Gabon to assess virological failure (VF) defined by a VL result ≥1000 copies/ml and DRMs among adult patients living with non-B HIV-1 strains and receiving first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy for at least 12 months. Risk factors associated with VF and DRMs were assessed. Results: Between March 2010 and March 2011, a total of 375 patients were consecutively enrolled from two decentralized (one semirural and one rural) HIV care centres. Median time on ART was 33.6 months (range, 12-107). Overall, the rate of VF was 41.3% (36.4-46.4). Among viremic patients, 56.7% (80/141) had at least one DRM and 37.6% had dual-class resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and NNRTIs. The most frequent DRMs were K103N/S (46.1%) and M184V/I (37.6%). Thymidine analogue mutations were found in 10.6%. Independent risk factors associated with VF were being followed up at the semirural centre ( P =0.033), having experienced unstructured treatment interruptions ( P =0.0044), and having low CD4 counts at enrolment ( P <0.0001). A longer time on ART ( P =0.0008) and being followed up at the rural centre ( P =0.021) were risk factors for DRMs. Conclusions: This is the first study conducted in Gabon providing VF rates and DRM patterns in adult patients receiving first-line ART. In sub-Saharan Africa, where NNRTI-based regimens are recommended as the standard for first-line ART, strengthening virological monitoring together with preventing unplanned treatment interruptions are a global public health priority. Keywords: HIV; Africa; antiretroviral therapy; viral load; resistance. (Published: 28 November 2012) Citation: Liegeois F et al. Journal of the International AIDS Society 2012, 15 :17985 http://www.jiasociety.org/index.php/jias/article/view/17985 | http://dx.doi.org/10.7448/IAS.15.2.17985

46 citations


Journal ArticleDOI
TL;DR: Virological failure combined with drug resistance after resumption of first-line ART occurred in 24.1% of the patients with treatment interruption, requiring a switch to protease inhibitor-based second-line therapy.
Abstract: Background. Since 2004, Malawi has rapidly scaled up access to antiretroviral therapy (ART) in the national program following a public health approach with limited laboratory monitoring. We examined virological outcomes in patients with treatment interruption at 2 clinics of the Lighthouse Trust, Lilongwe, Malawi. Methods. We evaluated patients who resumed first-line ART after having at least 1 treatment interruption documented in the electronic data system in 2008–2009. Viral load (VL) was analyzed at least 2 months after resumption of ART. For VL ≥1000 copies/mL, drug-resistance genotype was characterized using the Stanford database. Results. Between June and November 2009, we enrolled 133 patients (58.7% female) with a mean age of 38.4 years. Mean duration of ART prior to treatment interruption was 14.3 months. After a minimum of 2 months following ART resumption, VL was undetectable in 81 (60.9%) patients, was 400–1000 copies/mL in 12 (9.0%) patients, and was ≥1000 copies/mL in 40 (30.1%) patients. Genotyping and drug-resistance testing were successfully performed for 36 of 40 patients, all carrying human immunodeficiency virus type 1 subtype C. Relevant mutations affecting nonnucleoside reverse transcriptase inhibitors were found in 32 of 133 (24.1%) patients and combined with relevant nucleoside reverse transcriptase mutations in 27 of 133 (20.3%) patients. Conclusions. Virological failure combined with drug resistance after resumption of first-line ART occurred in 24.1% of the patients with treatment interruption, requiring a switch to protease inhibitor–based second-line therapy. Patients with treatment interruption should receive VL assessment after resumption of ART to detect treatment failure and to reduce development and spread of drug resistance.

43 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)

1,453 citations


Journal ArticleDOI
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.
Abstract: BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naive adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.

1,113 citations


Journal ArticleDOI
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.
Abstract: WHO has proposed 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. In this approach, standardised simplified treatment protocols and decentralised service delivery enable treatment to be delivered to large numbers of HIV-positive adults and children through the public and private sector. Simplified tools and approaches to clinical decision-making, centred on the "four Ss"-when to: start drug treatment; substitute for toxicity; switch after treatment failure; and stop-enable lower level health-care workers to deliver care. Simple limited formularies have driven large-scale production of fixed-dose combinations for first-line treatment for adults and lowered prices, but to ensure access to ART in the poorest countries, the care and drugs should be given free at point of service delivery. Population-based surveillance for acquired and transmitted resistance is needed to address concerns that switching regimens on the basis of clinical criteria for failure alone could lead to widespread emergence of drug-resistant virus strains. The integrated management of adult or childhood illness (IMAI/IMCI) facilitates decentralised implementation that is integrated within existing health systems. Simplified operational guidelines, tools, and training materials enable clinical teams in primary-care and second-level facilities to deliver HIV prevention, HIV care, and ART, and to use a standardised patient-tracking system.

661 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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Journal ArticleDOI
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)

339 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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Journal ArticleDOI
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

302 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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