High Prevalence of Genotypic and Phenotypic HIV-1 Drug-Resistant Strains Among Patients Receiving Antiretroviral Therapy in Abidjan, Côte d'Ivoire

Adje, Christiane; Cheingsong, Rachanee; Roels, Thierry H.; Maurice, Chantal; Djomand, Gaston; Verbiest, W; Hertogs, Kurt; Larder, Brendan A.; Monga, Ben; Peeters, Martine; Eholié, Serge; Bissagene, Emmanuel; Coulibaly, Makan; Respess, Richard; Wiktor, Stefan Z.; Chorba, Terence; Nkengasong, John N.

doi:10.1097/00126334-200104150-00018

Cited by 99 publications

(51 citation statements)

References 15 publications

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“…These findings are consistent with previous studies that have reported similar rates of acquired drug resistance mutations in Cameroon (8,23) and other African countries with similar ART programs (10,31,32). The most prevalent mutations identified were M184V and K103N.…”

Section: Discussionsupporting

confidence: 93%

Use of Amplification Refractory Mutation System PCR Assay as a Simple and Effective Tool To Detect HIV-1 Drug Resistance Mutations

Nanfack

Agyingi

Noubiap³

et al. 2015

J Clin Microbiol

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Access to genotyping assays to determine successful antiretroviral treatment (ART) is limited in resource-constrained settings by high cost, suggesting the need for a cost-effective and simplified method to identify HIV-1 drug resistance (HIVDR) mutations. In this study, an amplification refractory mutation system (ARMS)-PCR assay was developed and used to investigate the most frequent HIVDR mutations affecting first-line ART in settings where WHO ART guidelines are applied. Seventy-five HIV-positive (HIV ؉ ) samples from Cameroon were used to assess the performance of this assay. Sequencing of HIV-1 reverse transcriptase was simultaneously performed for comparison, and discordant samples were tested with a Trugene HIV-1 genotyping kit. The ARMS-PCR assay was able to detect M184V, T215Y/F, K103N, and Y181C mutations with sensitivities of 96.8%, 85.7%, 91.3%, and 70%, respectively, and specificities of 90.6%, 95%, 100%, 96.9%, respectively, compared with data on sequencing. The results indicated the highest positive predictive value for K103N (100%) and the highest negative predictive value for M184V (97.5%). ARMS-PCR's limits of detection for mutations M184V, T215Y/F, K103N, and Y181C were <75 copies/ml, 143 copies/ ml, 143 copies/ml, and 836 copies/ml, respectively. ARMS-PCR efficiently identified mutations in individuals harboring different HIV-1 clades (CRF02_AG and non-CRF02_AG). In addition, this approach was more cost-effective than other genotyping assays. The high throughput, the cost-effectiveness, and the simplicity of the ARMS-PCR assay make it a suitable tool to monitor HIVDR patterns in resource-constrained settings with broad HIV-1 genetic diversity. In recent years, significant progress has been made in the treatment of HIV-infected patients. Gains in antiretroviral treatment have been achieved in low-and middle-income countries with more than 9.7 million people living with HIV/AIDS, 7.2 million of whom lived in sub-Saharan Africa as of the end of 2012 (35). This scaling up of antiretroviral therapy in resource-constrained settings, where the logistics of medication disbursement and patient follow-up are not always optimal, results in the emergence and transmission of HIV drug-resistant variants, thus providing obstacles to successful antiretroviral treatment (ART) programs (1). The monitoring of HIV drug-resistant mutations in developed countries is an important aspect of clinical management of HIV infection. In these developed countries, sequencing-based drug resistance assays are used to select the most appropriate regimens when initiating or switching ART (2, 3). In resource-constrained settings, due to high cost, only a limited number of HIV drug resistance mutation tests are performed for patient management. In such countries, the majority of tests are used for research purposes or for surveillance of HIV-1 drug resistance (HIVDR) mutations recommended by WHO to update antiretroviral therapy policies (4, 5).Resource-constrained settings use the WHO public health approach for the treatment of...

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Section: Discussionsupporting

confidence: 93%

Use of Amplification Refractory Mutation System PCR Assay as a Simple and Effective Tool To Detect HIV-1 Drug Resistance Mutations

Nanfack

Agyingi

Noubiap³

et al. 2015

J Clin Microbiol

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“…In countries where few patients are exposed to suboptimum treatment and a public-health approach is taken to HIV management, the potential for widespread viral resistance could be less likely than that in resourcerich settings. [42][43][44] Sentinel monitoring approaches to follow HIV resistance emergence in HAART programmes should be implemented where possible. 45 Our study presents several limitations mainly because it analyses the outcomes of an observational cohort with routine data monitoring.…”

Section: Discussionmentioning

confidence: 99%

Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment

Ferradini¹,

Jeannin

Pinoges³

et al. 2006

The Lancet

405

308

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“…We demonstrated that HIV pol can be efficiently amplified and genotyped from DBS collected from individuals with a wide range of plasma virus loads. These findings are important because genotypic testing from DBS may simplify drug resistance surveillance and monitoring in resource-limited settings (1,16,23). The establishment of efficient resistance surveillance networks in these settings represents an important public health tool that will help to assess the prevalence of HIV drug resistance and adjust treatment guidelines if needed.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Dried Blood Spots for Human Immunodeficiency Virus Type 1 Drug Resistance Testing

et al. 2007

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Dried blood spots (DBS) are simpler to prepare, store, and transport than plasma or serum and may represent a good alternative for drug resistance genotyping, particularly in resource-limited settings. However, the utility of DBS for drug resistance testing is unknown. We investigated the efficiency of amplification of large human immunodeficiency virus type 1 (HIV-1) pol fragments (1,023 bp) from DBS stored at different temperatures, the type of amplified product(s) (RNA and/or DNA), and the similarity between plasma and DBS sequences. We evaluated two matched plasma/DBS panels stored for 5 to 6 years at several temperatures and 40 plasma/DBS specimens collected from untreated persons in Cameroon and stored for 2 to 3 years at ؊20°C. The amplification of HIV-1 pol was done using an in-house reverse transcriptase-nested PCR assay. Reactions were done with and without reverse transcription to evaluate the contribution of HIV DNA to pol sequences from DBS. Amplification was successful for the DBS samples stored for 5 to 6 years at ؊20°C or at ؊70°C but not for those stored at room temperature. Thirty-seven of the 40 (92.5%) DBS from Cameroon were amplifiable, including 8/11 (72.7%) with plasma virus loads of <10,000 RNA copies/ml and all 29 with plasma virus loads of >10,000. Proviral DNA contributed significantly to DBS sequences in 24 of the 37 (65%) specimens from Cameroon. The overall similarity between plasma and DBS sequences was 98.1%. Our results demonstrate the feasibility of DBS for drug resistance testing and indicate that ؊20°C is a suitable temperature for long-term storage of DBS. The amplification of proviral DNA from DBS highlights the need for a wider evaluation of the concordance of resistance genotypes between plasma and DBS.The introduction of highly active antiretroviral therapy and the demonstration of dramatic improvements in human immunodeficiency virus (HIV)-and AIDS-related mortality and morbidity in North America and Europe have fueled international efforts to expand access to care and treatment in lessdeveloped countries. Several major initiatives to provide treatment in resource-limited settings, including the U.S. President's Emergency Plan for AIDS Relief and the Global Fund against AIDS, TB and Malaria, are now in progress (16). The implementation of these programs requires the development of appropriate and effective patient-monitoring systems, including surveillance for antiretroviral drug resistance. Sentinel drug resistance surveillance systems are important public health tools that can provide information on trends in the prevalence of resistance at the population level and can be used to modify treatment guidelines.Plasma and serum are considered the preferred specimen types for HIV type 1 (HIV-1) drug resistance testing. However, these types of specimens are not optimal in resource-limited settings where the equipment necessary for PCR amplification and sequencing may not be available at collection sites and resistance testing requires transportation of the samples to a refer...

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High Prevalence of Genotypic and Phenotypic HIV-1 Drug-Resistant Strains Among Patients Receiving Antiretroviral Therapy in Abidjan, Côte d'Ivoire

Cited by 99 publications

References 15 publications

Use of Amplification Refractory Mutation System PCR Assay as a Simple and Effective Tool To Detect HIV-1 Drug Resistance Mutations

Use of Amplification Refractory Mutation System PCR Assay as a Simple and Effective Tool To Detect HIV-1 Drug Resistance Mutations

Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment

Evaluation of Dried Blood Spots for Human Immunodeficiency Virus Type 1 Drug Resistance Testing

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