Emergence of Antiretroviral Therapy Resistance-Associated Primary Mutations Among Drug-Naive HIV-1-Infected Individuals in Rural Western Cameroon

Koizumi, Yusuke; Ndembi, Nicaise; Miyashita, Michiko; Lwembe, Raphael; Kageyama, Seiji; Mbanya, Dora; Kaptué, Lazare; Numazaki, Kei; Fujiyama, Yoshihide; Ishiguro, Hiroshi

doi:10.1097/01.qai.0000226793.16216.55

Cited by 30 publications

(12 citation statements)

References 34 publications

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“…Data regarding the transmission of drug-resistance mutations in the current study found five (24%) drugnaïve individuals who harbored viruses with genotypic drug-resistance mutations to NRTIs and/or NNRTIs. Earlier studies conducted in Cameroon found the rate of drug-resistance mutation transmission among drugnaïve individuals ranging between 4.9% and 9.8% [Koizumi et al, 2006;Vergne et al, 2006;Vessiere et al, 2006;Ndembi et al, 2008]. The present analysis reveals an increase in the rate of transmission of viral variants with drug-resistance mutations, which could be due in part to the increasing availability of ARV therapy in the community and/or poor adherence to treatment.…”

Section: Discussionmentioning

confidence: 46%

HIV‐1 reverse transcriptase drug‐resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon

Burda

Viswanath

Zhao

et al. 2009

Journal of Medical Virology

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The most common first-line, highly active anti-retroviral therapy (HAART) received by individuals infected with HIV-1 in Cameroon is the combination therapy Triomune, comprised of two nucleoside reverse transcriptase inhibitors (NRTI) and one non-NRTI (NNRTI). To examine the efficacy of these drugs in Cameroon, where diverse non-B HIV-1 subtypes and recombinant viruses predominate, the reverse transcriptase (RT) viral sequences in patient plasma were analyzed for the presence of mutations that confer drug resistance. Forty-nine HIV-1-positive individuals were randomly selected from those receiving care in HIV/AIDS outpatient clinics in the South-West and North-West Regions of Cameroon. Among the 28 patients receiving HAART, 39% (11/28) had resistance to NRTIs, and 46% (13/28) to NNRTIs after a median of 12 months from the start of therapy. Among those with drug-resistance mutations, there was a median of 14 months from the start of HAART, versus 9 months for those without; no difference was observed in the average viral load (10,997 copies/ml vs. 8,056 copies/ml). In contrast, drug-naïve individuals had a significantly higher average viral load (27,929 copies/ml) than those receiving HAART (9,527 copies/ml). Strikingly, among the 21 drug-naïve individuals, 24% harbored viruses with drug-resistance mutations, suggesting that HIV-1 drug-resistant variants are being transmitted in Cameroon. Given the high frequency of resistance mutations among those on first-line HAART, coupled with the high prevalence of HIV-1 variants with drug-resistance mutations among drug-naïve individuals, this study emphasizes the need for extensive monitoring of resistance mutations and the introduction of a second-line HAART strategy in Cameroon.

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Section: Discussionmentioning

confidence: 46%

HIV‐1 reverse transcriptase drug‐resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon

Burda

Viswanath

Zhao

et al. 2009

Journal of Medical Virology

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“…We are concerned that the current standard may lead to viral resistance and the need for more expensive ART regimens in the long term [42]. Given the lack of resistance testing in RLS, a modification to the proposed algorithm might be that patients identified with viral failure be re-tested after a period of intensive adherence support and only switched if they remain in viral failure.…”

Section: Discussionmentioning

confidence: 99%

Development and evaluation of a clinical algorithm to monitor patients on antiretrovirals in resource-limited settings using adherence, clinical and CD4 cell count criteria

Meya

Spacek

Tibenderana

et al. 2009

Journal of the International AIDS Society

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BackgroundRoutine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings.MethodsA cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression. A clinical algorithm using targeted viral load testing was constructed to identify patients for second-line ART. This algorithm was compared with the World Health Organization (WHO) guidelines, which use clinical and immunological criteria to identify failure in the absence of viral load testing.ResultsForty-nine (10%) had a viral load of >400 copies/mL and 39 (8%) had a viral load of >1000 copies/mL. An algorithm combining adherence failure (interruption >2 days) and CD4 failure (30% fall from peak) had a sensitivity of 67% for a viral load of >1000 copies/mL, a specificity of 82%, and identified 22% of patients for viral load testing. Sensitivity of the WHO-based algorithm was 31%, specificity was 87%, and would result in 14% of those with viral suppression (<400 copies/mL) being switched inappropriately to second-line ART.ConclusionAlgorithms using adherence, clinical and CD4 criteria may better allocate viral load testing, reduce the number of patients continued on failing ART, and limit the development of resistance.

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“…An initial One-Step RT-PCR for the pol (PR codons 1–99 and RT codons 1–237) region was performed using the Qiagen One-Step RT PCR Kit followed by a nested PCR amplification using in-house group M consensus primers as previously described [9,11]. …”

Section: Methodsmentioning

confidence: 99%

HIV-1 drug resistance-associated mutations among HIV-1 infected drug-naïve antenatal clinic attendees in rural Kenya

et al. 2013

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BackgroundAccess to antiretroviral therapy (ART) has increased dramatically in Sub-Saharan Africa. In Kenya, 560,000 people had access to ART by the end of 2011. This scaling up of ART has raised challenges to the Kenyan health system due to emergence of drug resistant viruses among those on treatment and possible onward transmission. To counter this, and come up with an effective treatment strategy, it has become vital to determine baseline mutations associated with drug resistance among the circulating strains of HIV-1in Kenya.MethodsThe prevalence of mutations associated with drug resistance in HIV-1 protease (PR) and reverse transcriptase (RT) regions from 188 HIV-1 infected treatment-naïve pregnant women was investigated in Kapsabet, Nandi Hills and Kitale district hospitals of Kenya. Blood samples were collected between April 2005 and June 2006. The HIV-1 pol gene was amplified using primers for HIV-1 PR and RT and sequenced using the BigDye chemistry. The mutations were analyzed based on the IAS algorithm as well as the Stanford University HIV Drug Resistance Database.ResultsBased on the PR and RT sequences, HIV-1 subtypes A1 (n=117, 62.2%), A2 (n=2, 1.1%), D (n=27, 14.4%), C (n=13, 6.9%), G (n=3, 1.6%), and possible recombinants (n=26, 13.8%) were detected. Mutations associated with nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside RTI (NNRTI)-resistance were detected in 1.6% (3 of 188) and 1.1% (2 of 188), respectively. Mutations associated with PI resistance were detected in 0.5% (1 of 188) of the study population.ConclusionThe prevalence of drug resistance among drug-naïve pregnant women in rural North Rift, Kenya in 2006 was 3.2%. Major drug resistance mutations associated with PIs, NRTIs and NNRTIs do exist among treatment-naïve pregnant women in North Rift, Kenya. There is a need for consistent follow-up of drug-naïve individuals in this region to determine the impact of mutations on treatment outcomes.

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Emergence of Antiretroviral Therapy Resistance-Associated Primary Mutations Among Drug-Naive HIV-1-Infected Individuals in Rural Western Cameroon

Cited by 30 publications

References 34 publications

HIV‐1 reverse transcriptase drug‐resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon

HIV‐1 reverse transcriptase drug‐resistance mutations in chronically infected individuals receiving or naïve to HAART in Cameroon

Development and evaluation of a clinical algorithm to monitor patients on antiretrovirals in resource-limited settings using adherence, clinical and CD4 cell count criteria

HIV-1 drug resistance-associated mutations among HIV-1 infected drug-naïve antenatal clinic attendees in rural Kenya

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