Protease Mutations in HIV-1 Non-B Strains Infecting Drug-Naive Villagers of Cameroon

Konings, Frank; Zhong, Ping; Agwara, Moise O.; Agyingi, Lucy; Zekeng, Léopold; Achkar, Jacqueline M.; Ewane, Leonard; Ze, E. Afane; Kinge, Thompson; Nyambi, Phillipe N.

doi:10.1089/088922204322749558

Cited by 35 publications

(23 citation statements)

References 18 publications

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“…The prevalence of these mutations in this population differs from those described for subtype B viruses in the same codons. Thus while the frequency of mutations at codons 10, 20, and 36 was 2-7% among drug naïve individuals with subtype B infection, it was higher (21.74, 100 and 105%) in this study and in other studies (Hirsch et al, 2000;Konings et al, 2004;Fonjungo et al, 2002) of non-B viruses. These data provide baseline information on the level of drug resistance in this environment, where access to antiretroviral therapy is being scaled up.…”

Section: Discussioncontrasting

confidence: 62%

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

Lar¹,

Lar²,

Bemis³

et al. 2007

Afr. J. Biotechnol.

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To determine HIV-1 subtypes and antiretroviral drug resistance mutations for 16 infected, pregnant women in Jos, Nigeria, part of pol (1040 bp) was amplified from patient PBMC DNA, sequenced and analyzed. Eight of the samples were subtype G, three were CRF02_AG and 2 were unique recombinant forms (URF) between G and CRF02_AG. The remaining consisted of 3 different strains: one was subtype C, and the other 2 were unrelated URF. Nearly full-length genome sequences were completed for 6 of the strains: 4 subtype G and 2 CRF02_AG. In the 14 drug-naïve subjects, no primary resistance-associated mutations were found, but secondary mutations were identified in 7 different codons of the gene coding for protease: PR K20I, M36I, L63A/P/V, V82I, L10M/I and I93L. In addition, the K238R mutation was identified in the reverse transcriptase gene of 3 viruses. The PR K20I and M36I mutations occurred in all of the strains, and the L10M and V82I mutations occurred only in subtype G. The mutation, I93L, was carried by subtype C viruses. Two of the women that had prior niverapine treatment, had primary resistance-associated mutations, RT M184V and K103N, archived in their proviral DNA several months after treatment cessation. The study reports a predominance of clade G and CRF02_AG, and provides many more examples of nearly full-length genome sequences for subtype G viruses from Nigeria. The ubiquitous presence of PI secondary resistance-associated mutations, as well as primary resistanceassociated mutations in 2 previously treated women, underscores the need to ensure adherence compliance to treatment.

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Section: Discussioncontrasting

confidence: 62%

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

Lar¹,

Lar²,

Bemis³

et al. 2007

Afr. J. Biotechnol.

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“…Unlike the case in developed countries, where antiretroviral regimens containing PIs are readily available, the first line of ART in Cameroon is the combination of two NRTIs plus one NNRTI. Very few patients in Cameroon are currently being or have been treated with PIs (1,(16)(17)(18). Konings et al (16) reported that only the minor mutations associated with PI resistance were detected among HIV-1-infected drug-naïve patients in Cameroon during the period of 2000 to 2002.…”

Section: Discussionmentioning

confidence: 99%

“…Very few patients in Cameroon are currently being or have been treated with PIs (1,(16)(17)(18). Konings et al (16) reported that only the minor mutations associated with PI resistance were detected among HIV-1-infected drug-naïve patients in Cameroon during the period of 2000 to 2002. Our study confirmed previous reports and describes a high frequency of minor mutations (isoleucine or valine at position 10 in CRF02_AG; K20I and M36I mutations), which were found in all sequences except one, i.e., the CMY-36 isolate classified as CRF11_cpx.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 in Yaoundé, Cameroon: Evidence of Major Drug Resistance Mutations in Newly Diagnosed Patients Infected with Subtypes Other than Subtype B

et al. 2008

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Prior to current studies on the emergence of drug resistance with the introduction of antiretroviral therapy (ART) in Cameroon, we performed genotypic analysis on samples from drug-naïve, human immunodeficiency virus (HIV)-infected individuals in this country. Of the 79 HIV type 1 (HIV-1) pol sequences analyzed from Cameroonian samples, 3 (3.8%) were identified as HIV-1 group O, 1 (1.2%) was identified as an HIV-2 intergroup B/A recombinant, and the remaining 75 (95.0%) were identified as HIV-1 group M. Group M isolates were further classified as subtypes A1 (n ‫؍‬ 4), D (n ‫؍‬ 4), F2 (n ‫؍‬ 6), G (n ‫؍‬ 12), H (n ‫؍‬ 2), and K (n ‫؍‬ 1) and as circulating recombinant forms CRF02_AG (n ‫؍‬ 41), CRF11_cpx (n ‫؍‬ 1), and CRF13_cpx (n ‫؍‬ 2). Two pol sequences were identified as unique recombinant forms of CRF02_AG/F2 (n ‫؍‬ 2). M46L (n ‫؍‬ 2), a major resistance mutation associated with resistance to protease inhibitors, was observed in 2/75 (2.6%) group M samples.

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“…Upon arrival, plasma was aliquoted and stored at Ϫ70°C. Sequence and phylogenetic analysis was performed on a subset of the cohort demonstrating that the predominant clade type was the circulating recombinant form, CRF02_AG (3,5).…”

Section: Methodsmentioning

confidence: 99%

Human Immunodeficiency Virus (HIV) Reverse Transcriptase Activity Correlates with HIV RNA Load: Implications for Resource-Limited Settings

Sivapalasingam¹,

Essajee

Nyambi

et al. 2005

J Clin Microbiol

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Measurement of human immunodeficiency virus type 1 (HIV-1) plasma RNA levels using Roche AMPLICOR version 1.5 (HIV RNA) is an integral part of monitoring HIV-infected patients in industrialized countries. These assays are currently unaffordable in resource-limited settings. We investigated a reverse transcriptase (RT) assay as a less expensive alternative for measuring viral burden that quantifies RT enzyme activity in clinical plasma samples. A comparison of RT and HIV RNA assays was performed on 29 paired plasma samples from patients living in the United States and 21 paired plasma samples from patients living in Cameroon. RT levels correlated significantly with plasma HIV RNA viral loads in plasma from U.S. patients (r ‫؍‬ 0.898; P < 0.001) and Cameroonian patients, a majority of whom were infected with HIV-1 clade type CRF02_AG (r ‫؍‬ 0.669; P < 0.01). Among 32 samples with HIV viral load of >2,000 copies/ml, 97% had detectable RT activity. One Cameroon sample had undetectable RNA viral load but detectable RT activity of 3 fg/ml. The RT assay is a simple and less expensive alternative to the HIV RNA assay. Field studies comparing these assays in resource-limited settings are warranted to assess the practicality and usefulness of this assay for monitoring HIV-infected patients on antiretroviral therapy.Human immunodeficiency virus (HIV) plasma viral load measurement is an integral part of monitoring infected patients in industrialized countries to determine the need to initiate or change antiretroviral (ARV) therapy. A commonly used Food and Drug Administration-approved assay, the Roche AMPLICOR version 1.5 (HIV RNA), is unaffordable for most patients in resource-limited settings. This HIV RNA assay uses nucleic acid amplification by PCR of conserved gene sequences, including non-clade B sequences (4, 9). One alternative to measuring RNA copies is to measure the activity of the virus-encoded reverse transcriptase enzyme (RT). An RT assay kit, ExaVir Load version 2, is currently available and distributed in Africa, but no published studies to date have correlated version 2 of the RT assay with HIV RNA viral load. We describe this correlation in plasma samples from HIVinfected patients from New York and Cameroon. MATERIALS AND METHODSPlasma samples from HIV-infected patients in New York City and Cameroon. New York City. Twenty-nine anonymous plasma samples from HIV-infected persons attending New York University Medical Center in 2004 were studied. Specimens were presumed to contain predominantly clade B HIV-1 virus, although clade analysis was not performed on these samples. While information on clinical symptoms or antiretroviral therapy history was not available for this anonymous sample, a large proportion of patients attending this clinic receive antiretroviral therapy. All samples were processed within 6 h and stored at Ϫ70°C.Cameroon. Twenty-one anonymous plasma samples from Bamenda, Cameroon, were obtained as part of a larger study (3). All patients were antiretroviral treatment naïve. Blood was collecte...

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Protease Mutations in HIV-1 Non-B Strains Infecting Drug-Naive Villagers of Cameroon

Cited by 35 publications

References 18 publications

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

HIV subtype and drug resistance patterns among drug nave persons in Jos, Nigeria

Molecular Characterization of Human Immunodeficiency Virus Type 1 (HIV-1) and HIV-2 in Yaoundé, Cameroon: Evidence of Major Drug Resistance Mutations in Newly Diagnosed Patients Infected with Subtypes Other than Subtype B

Human Immunodeficiency Virus (HIV) Reverse Transcriptase Activity Correlates with HIV RNA Load: Implications for Resource-Limited Settings

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