Prevalence Of HIV Drug Resistance Research Articles

HIV-1 drug-resistant mutations and related risk factors among HIV-1-positive individuals experiencing treatment failure in Hebei Province, China

BackgroundTo understand HIV-1 drug resistance in 11 prefectures of Hebei Province, China, we implemented a cross-sectional HIV-1 molecular epidemiological survey.MethodsBlood samples were collected from 122 newly diagnosed drug-naïve HIV-1-positive individuals and 229 antiretroviral therapy (ART)-failure individuals from 11 prefectures in Hebei Province, China. Patient demographic data were obtained via face-to-face interviews using a standardized questionnaire when blood samples were collected. Genotyping of HIV-1 drug resistance (DR) was implemented using an in-house assay.ResultsIn this study, the overall prevalence of HIV-1 DR was 35.5%. The prevalence of HIV-1 DR in participants experiencing treatment failure and ART-naïve participants was 51.9 and 5.9%, respectively. Mutations in protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), and non-NRTI (NNRTIs), as well as dual and multiple mutations were extensively seen in participants experiencing treatment failure. The proportions of NNRTI mutations (χ2 = 9.689, p = 0.002) and dual mutations in NRTIs and NNRTIs (χ2 = 39.958, p < 0.001) in participants experiencing treatment failure were significantly higher than those in ART-naïve participants. The distributions of M184V/I and M41L mutations differed significantly among three main HIV-1 genotypes identified. Viral load, symptoms in the past 3 months, CD4 counts, transmission route, and the duration of ART were found to be associated with HIV-1 DR.ConclusionsOur results suggest that new prevention and control strategies should be formulated according to the epidemic characteristics of HIV-1-resistant strains in Hebei Province, where antiretroviral drugs are widely used.

An Alarmingly High Proportion of HIV-1 Isolates Carrying Mutations Corresponding to Resistance to Antiretroviral Drugs among HIV-Positive High-Risk Groups in Central Vietnam: a Substudy of the National Sentinel Survey.

We studied the prevalence of HIV drug resistance among high-risk groups such as injecting drug users (IDUs), female sex workers (FSWs), and men having sex with men (MSM) in central Vietnam. We used HIV-positive blood samples from 2012-2013 sentinel surveillance surveys. Study subjects were screened for HIV infection by standardized screening assays, and the HIV-positive samples were further tested for HIV viral load and drug-resistance mutations (DRMs) by in-house assays. DRMs were identified using the Stanford University online sequence analysis tool. Their risk behaviors were also investigated. During the study period, 6,016 (high-risk) subjects were screened, and 97 tested positive for HIV infection (IDUs: n = 63, 3.0%; FSWs: n = 24, 0.9%; and MSM: n = 10, 1.0%). Ninety-two of the 97 samples (45 from 2012 and 47 from 2013) were available for further testing. HIV RNA was detected in 56 (60.9%) of the 92 samples, and drug resistance genotyping was successfully performed on 40 (71.4%) samples. All these isolates were subtype CRF01_AE, except for 1 (2.5%) IDU whose HIV belongs to subtype B. Thirteen individuals (32.5%) were carrying HIV with at least 1 DRM: 9 IDUs, 1 FSW, and 3 MSM. Thus, HIV seroprevalence among high-risk individuals in central Vietnam is low, but a high proportion of drug resistant HIV-1 isolates is observed in the high-risk group.

Pretreatment HIV-1 drug resistance in Argentina: results from a surveillance study performed according to WHO-proposed new methodology in 2014-15.

In Argentina, current national guidelines recommend starting with NNRTI-based regimens. Recently, there have been some local reports regarding concerning levels of NNRTI-transmitted resistance, but surveillance has never been carried out at a national level. To determine the prevalence of HIV drug resistance in people starting ART in Argentina using a WHO-proposed methodology. This was a cross-sectional, nationally representative study. Twenty-five antiretroviral-dispensing sites throughout the country were randomly chosen to enrol at least 330 persons starting ART, to generate a point prevalence estimate of resistance-associated mutations (RAMs) with a 5% CI (for the total population and for those without antiretroviral exposure). All consecutive patients older than 18 years starting or restarting ART in the chosen clinics were eligible. Samples were processed with Trugene and analysed using the Stanford algorithm. Between August 2014 and March 2015, we obtained 330 samples from people starting ART. The mean ± SD age was 35 ± 11 years, 63.4% were male, 16.6% had prior antiretroviral exposure and the median (IQR) CD4 count was 275 cells/mm3 (106-461). The prevalence of RAMs found was 14% (±4%) for the whole population (3% NRTI-RAMs; 11% NNRTI-RAMs and 2% PI-RAMs) and 13% (±4%) for those without prior antiretroviral exposure (3%, 10% and 2%, respectively). The most common mutation was K103N. This surveillance study showed concerning levels of HIV drug resistance in Argentina, especially to NNRTIs. Due to this finding, Argentina's Ministry of Health guidelines will change, recommending performing a resistance test for everyone before starting ART. If this is taken up properly, it also might function as a continuing surveillance tool.

Shift in HIV/AIDS Epidemic in Southeastern China: A Longitudinal Study from 1987 to 2015.

Objective: The aim of this study was to investigate the shift in the epidemiological features of HIV/AIDS during the last three decades in Fujian Province, southeastern China, so as to provide evidence for the development of novel HIV/AIDS control strategies. Methods: Data pertaining to the conventional surveillance, sentinel surveillance and epidemiological survey in Fujian Province during the period from 1987 to 2015 were collected. The epidemiological trends were described, and the subtypes of HIV strain were genotyped. In addition, the response to antiretroviral therapy was evaluated, and HIV genotypic resistance was assayed. Results: There was an increasing trend observed in the reported cases of HIV/AIDS in Fujian Province. From 1987 to the end of 2015, a total of 8651 HIV/AIDS cases were reported across the province, with totally 1557 deaths found. Among the total cases, the ratio of male/female cases was 3.7:1, which appeared to be an increasing trend; 77.1% cases were detected in young and middle-aged populations aged 19 to 50 years, however, the new HIV infections recently tended to occur in young people aged 15 to 18 years and in populations aged 50 years and older. Among all infected individuals, 49.3% were married, however, the percentage of unmarried cases increased from 6.67% before 1994 to 40.1% in 2015; 64.8% had junior high school education or lower, however, the proportion of HIV/AIDS cases with junior college education or above gradually increased from 6.5% in 2009 to 21.4% in 2015. The reported HIV/AIDS cases were predominantly found in coastal regions; however, a rapidly increasing trend was seen in the number of HIV/AIDS cases in inland regions, and the geographical variation of the cases gradually reduced. There were multiple routes of HIV transmission found in Fujian Province, and 94.2% infections were sexually transmitted, with a large increase in the percentage of male homosexual transmission. A variety of HIV-1 subtypes were genotyped in the province during the study period, and CRF01-AE and CRF07-BC intersubtype recombinant forms were predominant; however, a declining trend in the proportion of HIV-1 CRF01-AE recombinant virus and a significant rise in the proportion of HIV-1 CRF07-BC recombinant virus were observed. Over 90% HIV inhibition was found in all cases receiving antiretroviral therapy during the period from 2011 to 2015, indicating a low prevalence of HIV drug resistance. Conclusions: An increasing trend is still observed in the HIV/AIDS epidemics in Fujian Province, southeastern China. However, the epidemiological pattern of HIV/AIDS has recently changed in the province, and effective control interventions targeting the shift in the epidemiological features of HIV/AIDS should therefore be implemented to control the spread of the epidemic.

Prevalencia de la resistencia genotípica a los fármacos antirretrovirales en pacientes VIH positivos de Tegucigalpa

El objetivo de la investigación fue determinar la prevalencia de resistencia del VIH a las drogas antirretrovirales en pacientes tratados y no tratados. Para tal efecto, se analizaron 100 muestras de pacientes VIH positivos, 50 previos a iniciar tratamiento y 50 bajo tratamiento con evidencia de falla terapéutica, de Tegucigalpa.Secuencias del gen pol del VIH-1 fueron generadas para determinar la presencia de mutaciones asociadas a resistencia, utilizando la herramienta calibrada para la vigilancia de la resistencia propuesta por la OMS para pacientes pretratados y la lista de mutaciones de la base de datos de Stanford para pacientes bajo tratamiento.Los resultados muestran que la prevalencia de farmacorresistencia en pacientes previos a iniciar tratamiento fue del 19 % [IC 95 %: 9-33 %], el 8.3 % presentaron mutaciones contra los NRTI, el 12.5 % contra los NNRTI y el 6.25 % contra los PI. Las mutaciones con mayor frecuencia fueron: M184V, K103N, M46I. La prevalencia de mutaciones asociadas a resistencia en los pacientes en falla terapéutica fue del 82 % [IC 95 %:60-90 %], el 58 % contra los NRTI, 74 % contra los NNRTI y el 22 % contra los PI.En conclusión, se observó un marcado aumento en la prevalencia de mutaciones asociadas a resistencia en pacientes no tratados, comparada con estudios anteriores, lo cual es de mucha preocupación, ya que limita la eficacia del tratamiento de primera línea. Aunque la prevalencia de resistencia adquirida en pacientes con falla terapéutica se mantiene ligeramente constante, sigue siendo alta, requiriendo de cambios de tratamiento a segunda o tercera línea en estos pacientes, ocasionando un impacto económico en la salud pública.Revista Ciencia y Tecnología, N° 15, diciembre 2014: 147-160

Antiretroviral Treatment and Resistance Patterns in HIV-Infected Children.

Paediatric HIV-infected patients have higher risk of developing resistance to antiretroviral drugs, and from public health perspective, drug resistance remains a limiting factor for effective management of HIV infection in children. We reviewed the current evidences available on the antiretroviral treatment and resistance patterns in HIV-infected children. Prevalence of HIV drug resistance varied among the three main classes of antiretroviral drugs, namely nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors in both treatment naïve and treatment-experienced children in different countries. Most of the patients with extensive triple-class drug-resistant mutations were found to be considerably exposed to the three main classes of antiretroviral agents. Identification of genetic factors linked with susceptibility to perinatal transmission of HIV may be key in understanding the development of resistance due to waning antiviral effectiveness. Children who were less likely to achieve viral re-suppression were more likely to have resistance mutations. Newer drugs such as etravirine can be used as alternatives in case of resistance to efavirenz while newly developed diagnostic method such as next-generation sequencing is a platform for improving quality of detections especially minor variant drug resistance mutations.

Genetic Diversity and Drug Resistance Among Antiretroviral Treatment-Failed Individuals from 2010 to 2012 in Honghe, China.

The most common antiretroviral treatment (ART) received by individuals infected with HIV-1 in China is the combination therapy, comprised of nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs). To assess the prevalence of HIV-1 drug resistance and subtypes in Honghe of Yunnan, China, patient plasmas from ART-failed individuals were collected from January 2010 to December 2012. Genotyping was conducted using an in-house assay on patient plasmas. A total of 254 pol sequences were obtained. The prevalence of drug resistance was 47.2% in ART-failed individuals. Of these drug-resistant individuals, 51.7% harbored HIV strains dually resistant to NRTIs and NNRTIs or protease inhibitors (PIs) (34.2% for NNRTIs and 14.2% for NRTIs). Mutations such as M184V, A62V, T69Ins, K103N, Y181C, and G190A were common among the ART-failed individuals. The frequencies of M184V, A62V, and K103N were 20.5%, 11.0%, and 23.6%, respectively. The most common subtypes in Honghe were CRF08_BC (68.50%) and CRF07_BC (12.20%). The subtypes were almost consistent in different time points for one individual. When receiving ART for 6-12 months, the frequency of HIV-1 drug-resistant variants ranked first. This study shows that the high prevalence of HIV drug resistance observed among the ART-failed individuals should be of increasing concern (monitoring of resistance mutations) in ART regions and facilitate developing novel strategies for prevention and control of HIV infection in China.

Trends in Prevalence of HIV-1 Drug Resistance in a Public Clinic in Maputo, Mozambique.

BackgroundAn observational study was conducted in Maputo, Mozambique, to investigate trends in prevalence of HIV drug resistance (HIVDR) in antiretroviral (ART) naïve subjects initiating highly active antiretroviral treatment (HAART).Methodology/Principal FindingsTo evaluate the pattern of drug resistance mutations (DRMs) found in adults on ART failing first-line HAART [patients with detectable viral load (VL)]. Untreated subjects [Group 1 (G1; n=99)] and 274 treated subjects with variable length of exposure to ARV´s [6–12 months, Group 2 (G2;n=93); 12-24 months, Group 3 (G3;n=81); >24 months (G4;n=100)] were enrolled. Virological and immunological failure (VF and IF) were measured based on viral load (VL) and T lymphocyte CD4+ cells (TCD4+) count and genotypic resistance was also performed. Major subtype found was C (untreated: n=66, 97,06%; treated: n=36, 91.7%). Maximum virological suppression was observed in G3, and significant differences intragroup were observed between VF and IF in G4 (p=0.022). Intergroup differences were observed between G3 and G4 for VF (p=0.023) and IF between G2 and G4 (p=0.0018). Viral suppression (<50 copies/ml) ranged from 84.9% to 90.1%, and concordant VL and DRM ranged from 25% to 57%. WHO cut-off for determining VF as given by 2010 guidelines (>5000 copies/ml) identified 50% of subjects carrying DRM compared to 100% when lower VL cut-off was used (<50 copies/ml). Length of exposure to ARVs was directly proportional to the complexity of DRM patterns. In Mozambique, VL suppression was achieved in 76% of individuals after 24 months on HAART. This is in agreement with WHO target for HIVDR prevention target (70%).ConclusionsWe demonstrated that the best way to determine therapeutic failure is VL compared to CD4 counts. The rationalized use of VL testing is needed to ensure timely detection of treatment failures preventing the occurrence of TDR and new infections.

HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission.

The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs.

HIV-1 subtypes and drug resistance profiles in a cohort of heterosexual patients in Istanbul, Turkey.

Turkey is seeing a steady rise in rates of HIV infection in the country. The number of individuals with HIV/AIDS was greater than 7000 in 2014 according to data released by the Ministry of Health, and heterosexual contacts were reported to be the main transmission routes. Istanbul has the highest number of reported cases of HIV infection. The aim of the study was to determine the prevalence of HIV-1 drug resistance in 50 heterosexual patients from Istanbul. The most prevalent subtype was found to be subtype B (56.2 %). Resistance-associated mutations were found in 14 patients with 6/14 patients being therapy-experienced and 8/14 therapy naive at the time point of analysis. With increasing number of patients who require treatment and the rapid up-scaling of the antiretroviral therapy in Turkey, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.

Prevalence of HIV-1 drug resistance among patients failing first-line ART in Monrovia, Liberia: a cross-sectional study.

To assess the prevalence of acquired drug resistance in HIV-1-infected patients living in Monrovia, Liberia, who had clinical and/or immunological failure of first-line ART according to WHO criteria. Patients receiving ART for >1 year with clinical and/or immunological failure were included. Sequencing of protease and reverse transcriptase regions was performed using Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS) procedures and sequences were interpreted using the ANRS resistance algorithm. Ninety patients were enrolled. They had been receiving ART for a median time of 42 months and half were receiving zidovudine/lamivudine/nevirapine. Seventy-five per cent of patients were infected with CRF02_AG. Twenty-seven per cent of patients displayed a plasma viral load <50 copies/mL. Among the 66 patients with detectable viraemia, the median viral load was 4.7 log10 copies/mL (IQR = 3.0-5.6). The prevalence of NRTI and NNRTI resistance-associated mutations (RAMs) was 63% and 71%, respectively; and the median number of NRTI and NNRTI RAMs was 2 and 3, respectively. Two patients (4%) displayed viruses with PI RAMs. Regarding NRTI drug resistance, 29%, 38%, 63%, 29% and 25% of patients had viruses resistant to zidovudine, stavudine, lamivudine/emtricitabine, abacavir and tenofovir, respectively. Regarding the NNRTI drug class, 56%, 65%, 33% and 42% of patients had viruses resistant to efavirenz, nevirapine, etravirine and rilpivirine, respectively. The high prevalence of acquired drug resistance in patients followed in two centres of the Liberian capital city, documented after a median of 3 years on a first-line ART regimen, jeopardizes the activity of second-line regimens and highlights the need for virological monitoring in these settings.

Epidemiological and molecular characteristics of HIV infection among money boys and general men who have sex with men in Shanghai, China

To examine and compare the epidemiological and molecular characteristics of HIV infection between money boys (MBs) and general men who have sex with men (MSM) in Shanghai, China. Using a venue-based sampling strategy, a total of 535 MSM including 226 MBs and 309 general MSM were recruited to participate in a cross-sectional survey including a face-to-face questionnaire interview and HIV testing. Genotyping of HIV-1 pol gene was performed for HIV-positive participants. Compared with general MSM, MBs reported more sexual partners, more alcohol and drug use and more sex after alcohol or drug use. HIV prevalence was 10.7% overall, 14.6% for MBs and 7.8% for general MSM (p=0.011). Two independent multiple logistic regression analyses indicated that HIV infection was positively associated with non-Han ethnicity (Odds Ratio [OR]=4.79, 95% Confidence Interval [CI]: 1.08–21.28) and sex after drug use in the past 6months (OR=3.59, 95% CI: 1.50–8.61) among MBs, and with sex after drug use in the past 6months (OR=3.38, 95% CI: 1.10–10.34) among general MSM as well. HIV-1 pol gene was successfully amplified and sequenced for 52 (91.2%) of HIV-positive participants. Of them, 53.8% were genotyped as CRF01_AE, 36.5% as CRF07_BC and 9.6% as subtype B. Two CRF01_AE subtype-infected participants (3.8%), a 50years old MB and a 24years old general MSM, harbored viruses with a M46L mutation conferring resistance to protease inhibitors (PI). MSM particularly MBs in Shanghai, China were at high risk of HIV infection, underscoring an urgent need for joint intervention efforts for drug use and sexual behaviors. HIV drug resistance surveillance is also warranted although the relatively low prevalence of HIV drug resistance implies the effectiveness of current antiretroviral treatment regimen.

The Prevalence of HIV Drug Resistance among Treatment-failure Individuals and Treatment-naïve Individuals in China: A Meta-analysis

ObjectiveTo understand drug resistance prevalence among treatment-failure and treatment-naïve HIV-positive individuals in China. MethodsWe searched five electronic databases (Wanfang, CNKI, CQVIP, SinoMed, and Pubmed) for studies of HIV drug resistance. Random-effects models were carried out to estimate the prevalence of drug resistance among treatment-failure and treatment-naïve individuals, respectively. ResultsThe estimated nationwide rates of HIV drug resistance to any-class drugs among treatment-failure and treatment-naïve individuals were 57% (95% CI: 49%-65%) and 3.23% (95% CI: 2.47%-4.07%), respectively. Among the drug classes, the prevalence of resistance to PIs was low (1.45%; 95% CI: 0.73%-2.33%) in treatment-failure individuals, although high rates of resistance to NNRTIs (54%; 95% CI: 45%-63%) and NRTIs (40%; 95% CI: 32%-49%) were found. Resistance to any-class drugs, NNRTIs and NRTIs manifested regional differences, but resistance to PIs did not. Positive correlations were observed between resistance to NNRTIs and NRTIs among treatment-failure and treatment-naïve individuals, respectively. ConclusionThe prevalence of HIV drug resistance to NNRTIs and NRTIs among treatment-failure individuals was high. In contrast, the prevalence of drug resistance among treatment-naïve individuals was low. The epidemics of drug resistance matched current treatment strategies and interventions in China. Surveillance for HIV drug resistance is necessary to assess the sustainability and durability of current treatment regimens.

The prevalence of HIV-1 drug resistance among antiretroviral treatment naïve individuals in mainland China: a meta-analysis.

BackgroundSurveillance of drug resistance in antiretroviral treatment-naïve patients in China is needed to ensure optimal treatment outcomes and control of the human immunodeficiency virus (HIV) epidemic.MethodsA systematic literature search was conducted in English and Chinese through PubMed (English), China National Knowledge Infrastructure (Chinese), Chinese Biomedical Literature Database (Chinese), and Wanfang (Chinese). Random effects models were used to calculate the pooled prevalence of transmitted drug resistance and subgroup analyses examined prevalence estimates across time periods, study locations, and study populations.ResultsAnalysis of data from 71 studies (47 in Chinese and 24 in English) yielded a pooled prevalence of transmitted HIV drug resistance to any antiretroviral drug class of 3.64% (95% confidence interval [CI]: 3.00%–4.32%). Rates were significantly high at initial stage of free ART program from 2003 to 2005 (5.18%, 95%CI: 3.13%–7.63%), and were much lower among studies conducted in 2006–2008 (3.02%, 95%CI: 2.03%–4.16%). A slight increase was observed again in the most recent study period from 2009 to 2012 (3.68%, 95%CI: 2.78%–4.69%). Subgroup analysis revealed highest prevalence levels of transmitted drug resistance in Beijing city, and Henan and Hubei provinces (above 5%), and although differences in prevalence rates among risk groups were negligible, men who have sex with men were unique in their relatively large portion of protease inhibitor resistance, a second-line drug of limited availability in China.ConclusionsOverall prevalence of transmitted HIV drug resistance in China is classified as “low” by the World Health Organization. However regional and temporal variability suggest a more complex epidemic for which closer HIV drug resistance surveillance is needed. A nationwide HIV drug resistance surveillance system to monitor both treatment-experienced and treatment-naïve patients will be a cornerstone to ensure the effectiveness of treatment scale-up, particularly as China seeks to expand a national policy of antiretroviral treatment as prevention.

HIV virological failure and drug resistance among injecting drug users receiving first-line ART in China

ObjectiveTo explore HIV virological failure and drug resistance among injecting drug users (IDUs) receiving first-line antiretroviral treatment (ART) in China.DesignA series of cross-sectional surveys from 2003 to 2012 from the...

Burden of nonnucleoside reverse transcriptase inhibitor resistance in HIV-1-infected patients: a systematic review and meta-analysis.

The prevalence of HIV drug resistance varies with geographic location, year, and treatment exposure. This study generated yearly estimates of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in treatment-naive (TN) and treatment-experienced (TE) patients in the United States (US), Europe (EU), and Canada. Studies reporting NNRTI resistance identified in electronic databases and 11 conferences were analyzed in three groups: (1) TN patients in one of four geographic regions [US, Canada, EU countries with larger surveillance networks ("EU1"), and EU countries with fewer data ("EU2")]; (2) TE patients from any region; and (3) TN patients failing NNRTI-based treatments in clinical trials. Analysis data included 158 unique studies from 22 countries representing 84 cohorts of TN patients, 21 cohorts of TE patients, and 8 trials reporting resistance at failure. From 1995 to 2000, resistance prevalence in TN patients increased in US and EU1 from 3.1% to 7.5% and 0.8% to 3.6%, respectively. Resistance in both regions stabilized in 2006 onward. Little resistance was identified in EU2 before 2000, and increased from 2006 (5.0%) to 2010 (13.7%). One TN Canadian study was identified and reported resistance of 8.1% in 2006. Half of TN clinical trial patients had resistance after treatment failure at weeks 48-144. Resistance in TE patients increased from 1998 (10.1%) to 2001 (44.0%), then decreased after 2004. Trends in NNRTI resistance among TN patients show an increased burden in the US and some EU countries compared to others. These findings signify a need for alternate first-line treatments in some regions.

HIV drug resistance in newly diagnosed adults in a rural prefecture of eastern China.

Little is known about HIV drug resistance (HIVDR) in newly diagnosed HIV-infected adults in eastern China where the HIV epidemic is spreading predominantly through sexual contact. During 2008-2011, newly HIV-diagnosed adults in Taizhou prefecture, Zhejiang province in eastern China were examined for HIVDR by amplifying and sequencing the HIV-1 pol gene. Of 447 genotyped participants, 53·7% were infected with CRF01_AE, 20·1% with CRF07_BC, 12·5% with subtype B, and 11·6% with CRF08_BC. Most of the participants had one or more minor genetic mutations in the pol gene that are associated with HIVDR. Twelve (2·7%) participants met the standard guidelines of having low to high HIVDR, suggesting that the prevalence of HIVDR in newly HIV-diagnosed adults was low in the study area and current antiretroviral therapy (ART) regimens are likely to remain effective. However, given high frequency of minor HIVDR in HIV patients and the scaling up of ART programmes in China, larger HIVDR surveillance programmes are needed.

Drug resistance in the HIV-1-infected paediatric population worldwide: a systematic review.

Drug resistance monitoring of the paediatric HIV-1-infected population is required to optimize treatment success and preserve future treatment options. To explore the current knowledge of HIV drug resistance (HIVDR) in naive and pretreated HIV-1-infected paediatric populations across diverse settings and sampling time periods. PubMed database screened until May 2013. We selected publications including data on transmitted (TDR) and acquired drug resistance mutation (DRM) rates and/or pol sequences for HIVDR testing in paediatric patients. We recorded the children's country, age, study period, number of children with pol sequences, presence or absence of antiretroviral treatment (ART) at sampling time, viral region sequenced, HIVDR rate to the three main drug classes (single, doubleor triple), the considered resistance mutation list and performed assay, specimen type, HIV-1 variants and subtyping methodology when available. Forty-one selected studies showed HIVDR data from 2538 paediatric HIV-1-infected patients (558 naiveand 1980 pretreated) from 30 countries in Africa (11), Asia (6), America (10) and Europe (3). Both TDR and DRM prevalence were reported in 9 studies, only TDR in 6 and only DRM in 26. HIVDR prevalence varied across countries and periods. Most studies used in-house resistance assays using plasma or infected cells. HIV-1 non-B variants were prevalent in 18 paediatric cohorts of the 24 countries with reported subtypes. Only five countries (Uganda, Spain, the UK, Brazil and Thailand) presented resistance data in ≥200 patients. Systematic and periodic studies among infected children are crucial to design a more suitable first- or second-line therapy.

Correction: Prevalence of HIV-1 Drug Resistance among Women Screening for HIV Prevention Trials in KwaZulu-Natal, South Africa (MTN-009)

Correction: Prevalence of HIV-1 Drug Resistance among Women Screening for HIV Prevention Trials in KwaZulu-Natal, South Africa (MTN-009)

Long-term Effectiveness of Combination Antiretroviral Therapy and Prevalence of HIV Drug Resistance in HIV-1–infected Children and Adolescents in Rwanda

To determine the long-term outcomes of treatment and prevalence of genotypic drug resistance in children and adolescents on combination antiretroviral therapy. A cross-sectional study (September 2009 to October 2010) in which clinical, immunologic and virologic outcomes were assessed at a single-study visit and through patient records in a cohort of HIV-infected children and adolescents. Risk factors for clinical and immunologic responses and virologic outcome were evaluated using logistic regression, and the accuracy of clinical and immunologic criteria in identifying virologic failure was assessed. Four hundred twenty-four patients were enrolled with a median age of 10.8 years (range: 1.7-18.8) and a median duration on combination antiretroviral therapy of 3.4 years (range: 1.0-8.1). Thirty-three percent were stunted and 17% underweight. Eighty-four percent (95% confidence interval: 79-87) of children >5 years had CD4 ≥350 cells/mm and in 74% (95% confidence interval: 62-84) of younger children CD4% was ≥25. CD4 values and age at combination antiretroviral therapy initiation were independently associated with CD4 outcomes; 124 (29%) had HIV-1 RNA ≥1000 copies/mL, with no significant predictors. Sensitivity for weight-for-age and height-for-age and CD4 cells (<350/mm) remained under 50% (15-42%); CD4 cells showed the best specificity, ranging from 91% to 97%. Of 52 samples tested, ≥1 mutations were observed in 91% (nucleoside reverse transcriptase inhibitors) and 95% (non-nucleoside reverse transcriptase inhibitors); 1 to 2 thymidine analogue-associated mutations were detected in 16 (31%) and ≥3 thymidine analogue-associated mutations in 7 (13%). Nearly 1 in 3 children showed virologic failure, and >10% of the subgroup of children with treatment failure in whom genotyping was performed demonstrated multiple HIV drug resistance mutations. Neither clinical condition nor CD4 cells were good indicators for treatment failure.