Prevalence Of HIV Drug Resistance Research Articles

Transmitted antiretroviral drug resistance surveillance among newly HIV type 1-diagnosed women attending an antenatal clinic in Entebbe, Uganda.

To evaluate transmitted HIV-1 drug resistance and study the natural polymorphism in pol of HIV-1 strains of newly diagnosed women attending an antenatal clinic in Uganda we sequenced the protease and reverse transcriptase genes for 46 HIV-1 strains from the threshold surveillance. Of the 46 sequences analyzed, 48.0% were subtype A1 (n 22), 39.0% subtype D (n 18), 2.0% subtype A2 (n 1), 2.0% subtype C (n 1), and 9.0% intersubtype recombinant A1/D (n 4). Overall, many minor mutations were identified in the protease sequences. None of the strains had major associated mutations to any RTI drug or drug class interest after genotyping 37 samples of our cohort. The HIV drug resistance prevalence estimate in Entebbe following the HIVDR-TS methodology is less than 5% as set out by WHO guidelines.

Evaluation of transmitted HIV drug resistance among recently-infected antenatal clinic attendees in four Central African countries

The rapid expansion of antiretroviral treatment in resource-limited settings is raising concerns regarding the emergence and transmission of HIV drug resistance (HIVDR). We evaluated the extent of transmission of drug-resistant HIV strains in four Central African countries: the Republic of Congo, Central African Republic, Chad and Cameroon. The World Health Organization (WHO) HIVDR threshold survey was implemented in major treatment areas in each country. Pregnant women who were aged <25 years, who were at first pregnancy and who were HIV type-1-positive were enrolled at each site in 2006-2007 for genotyping. HIVDR prevalence was categorized using the WHO threshold survey binomial sequential sampling method. The prevalence of HIVDR in Brazzaville and Bangui sites could not be classified because the eligible sample number was not reached. HIVDR prevalence was low (<5%) in N'Djamena for all drug classes. In Yaoundé, we found one individual with the D67D/N mutation and two with K103N. HIVDR prevalence was categorized as low (<5%) for protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NRTIs), and moderate (> or =5-< or =15%) for non-NRTIs (NNRTIs). HIVDR prevalence in Douala was low for PIs and NNRTIs, and moderate for NRTIs as we identified one individual with M184V plus K101E plus G190A mutations and a second with D67D/N. The moderate HIVDR prevalence found in Yaoundé and Douala indicate that efforts should be made in Cameroon to prevent HIVDR; however, additional surveys are needed to confirm this trend. This study highlighted challenges presented by the WHO methodology, such as additional costs, workload, difficulties in acquiring even small sample numbers and the necessity for better quality assurance of HIV testing and record keeping at antenatal clinics.

Surveillance of transmitted HIV drug resistance in the Manzini-Mbabane corridor, Swaziland, in 2006

BackgroundIn resource-limited settings where anti-retroviral treatment (ART) is being scaled-up, the World Health Organization (WHO) recommends the surveillance of transmitted HIV drug resistance (HIVDR). We used the WHO's HIVDR threshold survey method to assess transmitted HIVDR in three antenatal clinic (ANC) sites along the corridor between the two most populous cities in Swaziland, where ART was introduced in 2003.MethodsFrom July–August 2006, remnant sera were aliquoted from HIV serosurvey specimens collected from 70 primagravidas &lt;25 years old attending ANC during the national HIV serosurvey. Genotyping was performed at the National Institute for Communicable Diseases, South Africa. Transmitted resistance was defined by the WHO's surveillance list of mutations. HIVDR prevalence was categorized using the WHO's threshold survey binomial sequential sampling method.ResultsAmong the 70 eligible specimens, 61 were sequenced – 60 (98%) were identified as subtype C and one as subtype B. No major nucleoside or non-nucleoside reverse transcriptase inhibitor mutations occurred among the first 34 consecutive specimens, which supported a transmitted resistance categorization to these drug classes as &lt;5%. One protease inhibitor mutation, M46I, was seen among the first 44 specimens, supporting a categorization of PI resistance as &lt;5%.ConclusionOur survey indicates that prevalence of transmitted HIVDR among recently infected pregnant women along the Manzini-Mbabane corridor is low (&lt;5%). Surveys will be carried out in this area biannually and may be extended to other areas. Surveys for transmitted resistance make up one element among a spectrum of activities to assess and support minimization of HIVDR.

Surveillance of transmitted HIV drug resistance among women attending antenatal clinics in Dar es Salaam, Tanzania

BackgroundIn resource-limited settings where antiretroviral treatment (ART) access is being scaled-up, the World Health Organization (WHO) recommends surveillance of transmitted HIV drug resistance (HIVDR). We used the WHO HIVDR threshold survey method to assess transmitted HIVDR in Dar es Salaam where ART was introduced in 1995 and where ∼11,000 people are currently on ART.MethodsFrom November 2005 to February 2006, dried blood spot (DBS) specimens were made from remnant specimens collected during the national HIV serosurvey from 60 primagravidas &lt;25 years old attending six antenatal clinics for routine syphilis testing. Genotyping was performed at the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. Protease and reverse transcriptase drug resistance mutations were identified using the Stanford University HIV drug resistance database. We used the National Institutes of Health genotyping tool for HIV-1 subtyping. HIVDR prevalence categorization was based on the WHO threshold survey binomial sequential sampling method.ResultsAmong the 60 eligible specimens collected, 50 DBS were successfully amplified using RT-PCR. Sequencing was performed on the first 39 specimens: 13 (33.3%) were subtype A1, 13 (33.3%) subtype C, and 4 (10.3%) subtype D, the remainder differed in the closest subtype based on protease versus reverse transcriptase. No resistance mutations were seen; HIVDR to all drug classes was categorized as &lt;5%.ConclusionsOur survey indicates that prevalence of transmitted HIVDR among recently infected pregnant women in Dar es Salaam is low (&lt;5%). The survey should be repeated during the next HIV sentinel survey in Dar es Salaam and extended to other regions where ART is being scaled up.

Transmitted HIV Drug Resistance in Pregnant Women

Given the relatively high prevalence of HIV drug resistance among treatment-naive individuals, the U.S. Department of Health and Human Services

Prevalence of HIV-1 Drug Resistance in Treated Patients

Surveillance of HIV-1 drug resistance in antiretroviral-treated patients is important from the public health perspective of the spread of resistance and to evaluate the proportion of patients for whom new drugs are needed. Patients were consecutively included in 28 centers in France and 1 center in Switzerland if they had a viral load measurement performed in June 2004, with a result >or=1,000 copies/mL. Reverse transcriptase, protease, and gp41 genes were sequenced, and resistance mutations were reported as listed on the Web site ( www.iasusa.org). The genotypic resistance results were interpreted by the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) and Stanford algorithms. The 498 patients included had been exposed to 9 (interquartile ratio [IQR]: 6 to 12) antiretroviral drugs. Patients' viruses harbored 4 nucleoside reverse transcriptase inhibitor (IQR: 1 to 6) and 4 protease inhibitor (PI; IQR: 2 to 8) resistance mutations, whereas 44% had at least 1 nonnucleoside reverse transcriptase inhibitor resistance mutation. The frequency of resistance to at least 1 drug was 88% with the ANRS algorithm and 83% with the Stanford algorithm. The frequencies of complete resistance to 1, 2, and 3 classes of drugs were 37%, 15%, and 4%, respectively, with the ANRS algorithm and 27%, 23%, and 24%, respectively, with the Stanford algorithm. The most important differences between algorithms were for PIs. Using the ANRS algorithm and extrapolation on the whole French database, 19% of all treated patients could contribute to the spread of resistance and 4% had complete resistance to 2 classes of antiretroviral drugs. The observed patterns of resistance are linked to a long-lasting history of antiretroviral therapy. The frequency of multiresistance can vary according to the interpretation systems.

Prevalence and risk factors associated with antiretroviral resistance in HIV‐1‐infected children

In the USA and West Europe, nearly 80% of HIV-1-infected adults, experiencing virologic failure, harbored virus strain resistant to at least one antiretroviral drug. Limited data are available on antiretroviral drug resistance in pediatric HIV infection. The aims of this study were to analyze prevalence of HIV-1 drug resistance and to identify risk factors associated with resistance in this population. Prevalence of genotypic resistance was estimated retrospectively in treated children who experienced virologic failure (with HIV-1-RNA > 500 copies/ml) followed in Necker hospital between 2001 and 2003. Among 119 children with resistance testing, prevalence of resistance to any drug was 82.4%. Resistance ranged from 76.5% to nucleoside reverse transcriptase inhibitor (NRTI), to 48.7% to non-nucleoside reverse transcriptase inhibitor (NNRTI) and 42.9% to protease inhibitor (PI). Resistance to at least one drug of two classes and three classes (triple resistance) was 31.9 and 26.9%, respectively. Resistance was not associated with geographic origin, HIV-1 subtype, and CDC status. In multivariate analysis, resistance to any drug remained associated independently with current low viral load and high lifetime number of past PI. Triple resistance was independently associated with the high lifetime number of past PI and with gender, particularly among children aged 11 years old or more with a prevalence seven times higher in boys than in girls. In conclusion, antiretroviral resistance is common among treated HIV-1-infected children and prevalence was similar with those observed in adult population in the same year period. However, adolescent boys seem to be at greater risk.

Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Peripheral Blood Mononuclear Cell Proviral DNA among Antiretroviral Treatment-Naive and Treatment-Experienced Patients from Pune, India

The prevalence of HIV drug resistance (HIVDR) mutations in the HIV protease (PR) and reverse transcriptase (RT) genes was estimated from peripheral blood mononuclear cells (PBMCs) in a study population of 25 antiretroviral (ARV) therapy-naive and 50 ARV-experienced chronically infected patients from Pune city, Maharashtra State, western India. Of the 75 study HIV-1 sequences, 73 belonged to subtype C and 2 to subtype A1. On phylogenetic analysis, the study subtype C sequences sub clustered randomly with different Indian and non-Indian subtype C sequences, emphasizing the HIV-1 subtype C pol gene diversity. The heterosexual route was the most common route of transmission (74.67%). There were no observable HIVDR mutations in ARV-naive patients. The ARV-experienced patients had a history of exposure to nucleoside reverse transcriptase inhibitor and nonnucleoside reverse transcriptase inhibitor combinations. At least one HIVDR mutation in RT was observed in 29 (80.55%) of ARV-experienced patients with evidence of failing therapy. M184V was the most common observed HIVDR mutation. No PR major mutations were observed among ARV-experienced patients. A higher prevalence of proviral HIVDR mutations in PBMCs was associated with irregular adherence to therapy (p < 0.05) and HIV-1 RNA levels > 1000 copies/ml (p < 0.001).

Overview of HIV drug resistance and its implications for China

At the end of 2005 an estimated 650 000 people in China were infected with HIV among whom 75 000 were in need of ART. The Division of Treatment and Care at the National Center for AIDS/STD Control and Prevention (NCAIDS) Chinese Center for Disease Control (CCDC) has been responsible for the overall scale up of the National Free ART Program. As of December 2005 a total of 20 453 patients in 28 provinces autonomous regions and special municipalities had benefited from this national program and received free ART. The increase in access to ART however is accompanied by the risk of drug resistance development. A small body of literature already documents HIV drug resistance in China in these treated populations. These preliminary findings are consistent with the development of drug resistance observed in developed countries soon after the initiation of wide-scale HIV treatment. Therefore it is imperative that clinicians understand the causes and implications of HIV resistance in both patientcare and in the public health perspective. (excerpt)

Prevalence of resistance-associated mutations in newly diagnosed HIV-1 patients in Greece

The prevalence of HIV-1 drug resistance mutations in naïve patients has been previously shown to differ greatly with the geographic origin. The purpose of this study was to prospectively estimate the prevalence of HIV-1 drug resistance in Greece by analyzing a representative sample of newly HIV-1 diagnosed patients, as part of the SPREAD collaborative study. Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 101 newly diagnosed HIV-1 patients, in Greece, during the period September 2002–August 2003, representing one-third of the total newly diagnosed HIV-1 patients in the same time period. The prevalence of HIV-1 drug resistance was estimated according to the IAS-USA mutation table taking into account all mutations in RT and only major mutations in PR region. The overall prevalence of resistance was 9% [95% confidence interval (CI): 4.2–16.2%]. The prevalence of mutations associated with resistance to NRTIs was 5% (95% CI: 1.6–11.2%), for NNRTIs was 4% (95% CI: 1.1–9.8%), while no major resistance mutations were found in PR. No multi-class resistance was detected in the study population. The prevalence of resistant mutations in the recent seroconverters was 22%. For two individuals, there was clear evidence for transmitted resistance based on epidemiological information for a known source of HIV-1 transmission. The prevalence of the HIV-1 non-B subtypes and recombinants was 52%.

The prevalence of antiretroviral drug resistance in the United States.

Antiretroviral therapy has dramatically reduced the morbidity and mortality of infection due to HIV. The emergence of drug-resistant virus has limited the usefulness of many drugs. To determine the prevalence of HIV drug resistance in the population of adults receiving care in the United States. HIV drug susceptibility assays were performed on plasma virus from a random sample representative of the 132500 HIV-infected American adults who had received medical care in early 1996 yet were viremic with > 500 copies/ml of HIV RNA in late 1998. A blood sample was obtained from 1797 patients who comprised a representative sample of the 208900 adults receiving urban care for HIV infection in early 1996 who survived to late 1998. The sampling procedure permitted weighting each evaluated patient to reflect demographic and other characteristics of the target population. We estimated that 132500 (63%) of the target population had HIV viremia of > 500 copies/ml. Among viremic patients, an estimated 76% had resistance to one or more antiretroviral drugs. The odds of resistance were significantly higher in patients with a history of antiretroviral drug use, advanced HIV disease, higher plasma HIV viral load and lowest CD4 cell count by self-report. The frequent selection for drug-resistant virus among viremic patients during the first 3 years of widespread use of potent antiretroviral combination therapy has significant implications for HIV treatment and transmission.

Analysis of prevalence of HIV-1 drug resistance in primary infections in the United Kingdom

Objectives: To identify changes since 1994 in the prevalence of resistance to anti-HIV drugs in primary HIV-1 infections in the United Kingdom.Design: Retrospective and prospective assessment of viruses obtained from...

Prevalence of HIV-1 drug resistance in antiretroviral-naive patients: a prospective study.

Prevalence of HIV-1 drug resistance in antiretroviral-naive patients: a prospective study.

Incidence and impact of resistance against approved antiretroviral drugs

More than 15 antiretroviral drugs are now available for clinical use, and have led to significant reductions in morbidity and mortality for HIV infected individuals. Nevertheless, antiviral drug resistance emerges to all these drugs, which limits their benefit. This review addresses the biological basis of antiretroviral drug resistance, and the prevalence of specific drug resistance associated mutations in patients treated with the three currently available classes of agents, namely nucleoside analogue reverse transcriptase inhibitors, non nucleoside reverse transcriptase inhibitors and protease inhibitors. In addition, data on prevalence of HIV drug resistance in untreated individuals published to date are summarised, and the implications of potential transmission of drug resistant HIV is discussed. Copyright © 2000 John Wiley & Sons, Ltd.

Incidence and impact of resistance against approved antiretroviral drugs.

More than 15 antiretroviral drugs are now available for clinical use, and have led to significant reductions in morbidity and mortality for HIV infected individuals. Nevertheless, antiviral drug resistance emerges to all these drugs, which limits their benefit. This review addresses the biological basis of antiretroviral drug resistance, and the prevalence of specific drug resistance associated mutations in patients treated with the three currently available classes of agents, namely nucleoside analogue reverse transcriptase inhibitors, non nucleoside reverse transcriptase inhibitors and protease inhibitors. In addition, data on prevalence of HIV drug resistance in untreated individuals published to date are summarised, and the implications of potential transmission of drug resistant HIV is discussed.