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.
Citations
More filters
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...
128 citations
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.
91 citations
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.
59 citations
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
56 citations
TL;DR: The low incidence rate of switching to second-line ART in sub-Saharan Africa suggests that the monitoring of patients under ART is challenging and that access to second -line ART is ineffective; efforts should be made to increase access toSecond- line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.
Abstract: OBJECTIVES Switching to second-line antiretroviral therapy (ART) largely depends on careful clinical assessment and access to biological measurements. We performed a systematic review and meta-analysis to estimate the incidence of switching to second-line ART in sub-Saharan Africa and its main programmatic determinants. METHODS We searched 2 databases for studies reporting the incidence rate of switching to second-line ART in adults living in sub-Saharan Africa. Data on the incidence rate of switching were pooled, and random-effect models were used to evaluate the effect of factors measured at the programme level on this incidence rate. RESULTS Nine studies (157,340 patients) in 21 countries were included in the meta-analysis. All studies considered patients under first-line ART and conditions to initiate ART were similar across studies. Overall, 3,736 (2.4%) patients switched to second-line ART. Incidence rate of switch was in mean 2.65 per 100 person-years (PY) (95% confidence interval: 2.01-3.30); it ranged from 0.42 to 4.88 per 100 PY and from 0 to 4.80 per 100 PY in programmes with and without viral load monitoring, respectively. No factors measured at the programme level were associated with the incidence rate of switching to second-line ART. CONCLUSION The low incidence rate of switching to second-line ART suggests that the monitoring of patients under ART is challenging and that access to second-line ART is ineffective; efforts should be made to increase access to second-line ART to those in need by providing monitoring tools, education and training, as well as a more convenient regimen.
51 citations
References
More filters
TL;DR: Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitor, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first- line treatment failure.
Abstract: Following large-scale roll-out of antiretroviral therapy in sub-Saharan Africa, the non-clinical efficacy of antiretroviral therapy has received little attention. We aimed to systematically review virological efficacy and drug-resistance outcomes of programmes of antiretroviral therapy in sub-Saharan Africa. 89 studies with heterogeneous design, definitions, and methods were identified. Overall, in on-treatment analysis, 10 351 (78%) of 13 288 patients showed virological suppression after 6 months of antiretroviral therapy, 7413 (76%) of 9794 after 12 months, and 3840 (67%) of 5690 after 24 months. Long-term virological data are scarce. Genotyping results were available for patients with virological failure (HIV-1 RNA greater than 1000 copies per mL). Most patients (839 of 849; 99%) were infected with a non-B HIV-1 subtype. However, drug-resistance patterns were largely similar to those in subtype B. Resistance profiles were associated with the antiretroviral drugs commonly used: the lamivudine-associated M184V mutation was most common, followed by K103N which is associated with non-nucleoside reverse transcriptase inhibitors. Thymidine-analogue mutations and the K65R mutation were less common. First-line antiretroviral therapy regimens used in sub-Saharan Africa are effective. Profiles of drug resistance suggest that a second-line treatment regimen based on protease inhibitors, with a backbone of nucleoside reverse transcriptase inhibitors, is a reasonable option for patients with HIV in sub-Saharan Africa who experience first-line treatment failure.
299 citations
"High prevalence of HIV-1 drug resis..." refers result in this paper
...However, the few studies reporting on ART using the public health approach showed more contrasted results, with virological succes after 12 months ranging from 50% to more than 90% [13,14]....
[...]
TL;DR: When clinical and CD4 cell count criteria are used to monitor first-line ART failure, extensive nucleoside reverse transcriptase inhibitor and nonnucleoside Reverse Transcriptase inhibitor resistance emerges, with most patients having resistance profiles that markedly compromise the activity of second- line ART.
Abstract: BACKGROUND: Over 150000 Malawians have started antiretroviral therapy (ART) in which first-line therapy is stavudine/lamivudine/nevirapine. We evaluated drug resistance patterns among patients failing first-line ART on the basis of clinical or immunological criteria in Lilongwe and Blantyre Malawi. METHODS: Patients meeting the definition of ART failure (new or progressive stage 4 condition CD4 cell count decline more than 30% CD4 cell count less than that before treatment) from January 2006 to July 2007 were evaluated. Among those with HIV RNA of more than 1000 copies/ml genotyping was performed. For complex genotype patterns phenotyping was performed. RESULTS: Ninety-six confirmed ART failure patients were identified. Median (interquartile range) CD4 cell count log10 HIV-1 RNA and duration on ART were 68 cells/microl (23-174) 4.72 copies/ml (4.26-5.16) and 36.5 months (26.6-49.8) respectively. Ninety-three percent of samples had nonnucleoside reverse transcriptase inhibitor mutations and 81% had the M184V mutation. The most frequent pattern included M184V and nonnucleoside reverse transcriptase inhibitor mutations along with at least one thymidine analog mutation (56%). Twenty-three percent of patients acquired the K70E or K65R mutations associated with tenofovir resistance; 17% of the patients had pan-nucleoside resistance that corresponded to K65R or K70E and additional resistance mutations most commonly the 151 complex. Emergence of the K65R and K70E mutations was associated with CD4 cell count of less than 100 cells/microl (odds ratio 6.1) and inversely with the use of zidovudine (odds ratio 0.18). Phenotypic susceptibility data indicated that the nucleoside reverse transcriptase inhibitor backbone with the highest activity for subsequent therapy was zidovudine/lamivudine/tenofovir followed by lamivudine/tenofovir and then abacavir/didanosine. CONCLUSION: When clinical and CD4 cell count criteria are used to monitor first-line ART failure extensive nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor resistance emerges with most patients having resistance profiles that markedly compromise the activity of second-line ART.
291 citations
"High prevalence of HIV-1 drug resis..." refers result in this paper
...This is in agreement with observations from a recent study in Malawi, which also showed clearly that when only clinical and CD4 count cell criteria are used to monitor first-line ART failure, extensive NRTI and NNRTI resistance emerges, with 23% patients having resistance profiles that compromise second-line ART [ 16 ]....
[...]
TL;DR: The World Health Organization (WHO) recommends a minimum-resource strategy for prevention and assessment of HIVDR in resource-limited countries, which should limit HIV drug resistance if programme effectiveness continues during scale-up.
Abstract: Antiretroviral treatment (ART) for HIV is being scaled up rapidly in resource-limited countries. Treatment options are simplified and standardized, generally with one potent first-line regimen and one potent alternate first-line regimen recommended. Widespread HIV drug resistance (HIVDR) was initially feared, but 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. ART interruptions must be minimized to maintain viral suppression on the first-line regimen for as long as possible. Lack of availability of appropriate second-line drugs is a concern, as is the additional accumulation of resistance mutations in the absence of viral load testing to determine failure. The World Health Organization (WHO) recommends a minimum-resource strategy for prevention and assessment of HIVDR in resource-limited countries. The WHO's Global Network HIVResNet provides standardized tools, training, technical assistance, laboratory quality assurance, analysis of results and recommendations for guidelines and public health action. National strategies focus on assessments to guide immediate public health action to improve ART programme effectiveness in minimizing HIVDR and to guide regimen selection. Globally, WHO HIVResNet collects and analyses data to support evidence-based international policies and guidelines. Financial support is provided by major international organizations and technical support from HIVDR experts worldwide. As of December 2007, 25 countries were planning or implementing the strategy; seven countries report results in this supplement.
243 citations
TL;DR: The WHO has developed a population-based HIVDR assessment and prevention strategy, which includes standardized HIVDR monitoring surveys in populations receiving first-line ART at sentinel sites, which will inform evidence-based decision making regarding national and global ART regimen selection and minimize the emergence of HIVDR at a population level.
Abstract: The World Health Organization (WHO) estimates that >2 million people will have started antiretroviral therapy (ART) by the end of 2006. As the development of some HIV drug resistance (HIVDR) is inevitable in populations taking ART, the emergence of HIVDR must be balanced against the benefits of providing ART, including improved health outcomes and decreased HIV/AIDS-associated morbidity and mortality. ART programmes should operate to minimize the emergence of HIVDR in populations receiving therapy and HIVDR itself must be monitored to ensure ongoing regimen efficacy. ART regimens in resource-limited settings are usually selected at the national level following a public health approach: generally only one first-line regimen with alternate regimen(s) incorporating within-class drug substitutions are available in the public sector. The WHO has developed a population-based HIVDR assessment and prevention strategy, which includes standardized HIVDR monitoring surveys in populations receiving first-line ART at sentinel sites. The WHO surveys monitor HIVDR prevention in sentinel sites by utilizing a standardized, minimum-resource prospective survey methodology to assess the success of adult and paediatric ART sites in preventing HIVDR emergence during the first year of ART. The surveys also identify associated factors that can be addressed at the level of the ART site or programme. WHO HIVDR monitoring surveys are designed to be integrated easily into a country's ongoing, routine HIV-related evaluation activities. Performed regularly at representative sites, the data generated will inform evidence-based decision making regarding national and global ART regimen selection and minimize the emergence of HIVDR at a population level.
193 citations
TL;DR: This study shows that clinical and biologic results similar to those seen in Western countries can be achieved and sustained during the long term in Africa.
Abstract: Objectives: To assess the long-term survival as well as the immunologic and virologic effectiveness adherence and drug resistance in HIV- infected patients receiving highly active antiretroviral therapy (HAART) in one of the oldest and best-documented African cohorts. Methods: A prospective observational cohort study included the first 176 HIV-1-infected adults followed in the Senegalese government-sponsored antiretroviral therapy initiative launched in August 1998. Patients were followed for a median of 30 months (interquartile range 21-36 months). HAART comprised 2 nucleoside reverse transcriptase inhibitors and either 1 protease inhibitor or 1 nonnucleoside reverse transcriptase inhibitor. Results: At baseline 92% of patients were antiretroviral naive and 82% had AIDS; the median CD4 count was 44 cells/mm(3) and median viral load was 202368 copies/mL. The survival probability was high (0.81 at 3 years; 95% CI 0.74-0.86) and was independently related to a baseline hemoglobin level <10 g/dL and a Karnofsky score <90%. Antiviral efficacy was consistently observed during the 3 years of treatment (-2.5 to -3.0 log(10) copies/mL; 60-80% of patients with viral load <500 copies/mL) and the CD4 count increase reached a median of 225 cells/mm(3). Most patients reported good adherence (80-90%). The emergence of drug resistance was relatively rare (12.5%). Conclusion: This study shows that clinical and biologic results similar to those seen in Western countries can be achieved and sustained during the long term in Africa. (authors)
174 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]....
[...]