Surveillance Of Transmitted HIV Drug Resistance Research Articles

Low prevalence of the transmitted HIV-1 drug resistance among newly diagnosed HIV-1 individuals in Jiangsu Province, China during 2009-2011.

BackgroundPrevalence of The transmitted HIV drug resistance (THDR) has been reported in many countries. In China, the low level THDR was found in only a few provinces. To know the transmitted HIV drug resistance in east of China, we investigated THDR during 2009–2011 in Jiangsu province of China.MethodsBetween January and August of 2009, 2010, and 2011, we consecutively collected 50, 54, 53 blood specimens respectively from qualified individuals at surveillance sentinel sites in Jiangsu province according to protocol of HIV Drug Resistance Threshold Survey (HIVDR-TS) recommended by WHO. The region of pol gene including protease and partial retro-transcriptase was amplified, sequenced and edited. Then the sequences were submitted to HIV drug resistance database to analysis transmitted HIV drug resistance mutations using Calibrated Population Resistance tool. The reference sequences of different HIV-1 subtypes were downloaded from HIV database and Genebank. The phylogenetic trees were inferred using the neighbor-joining method.ResultsOur results show that THDR has been at low level from 2009 to 2011, only K101E and V179D mutation was detected which did not belong to the major HIV-1 drug resistance mutations. Phylogenetic analysis showed that CRF01_AE is the predominant subtype, and followed by CRF07_BC and B subtype. Subtype B consists of the two distinct clusters.ConclusionsThe low level of THDR suggests that anti-retroviral treatment was implemented more effectively and THDR surveillance should be conducted two years later in Jiangsu province of China. CRF01_AE has become the predominant subtype and dual infection of HIV may be common in Jiangsu province.

Different trends of transmitted HIV-1 drug resistance in Madrid, Spain, among risk groups in the last decade

The presence of transmitted HIV drug resistance (TDR) threatens the efficacy of antiretroviral treatment. We aimed to assess the changes in TDR prevalence over the last decade in Madrid, Spain, to verify the role of the patients' risk groups in these changes. We analysed the trends of TDR between 2000 and 2011 in a cohort of 1,022 naïve HIV-infected patients in Madrid, Spain, whose pol sequences were available. They included, among others, 369 heterosexuals, 340 men who have sex with men (MSM), and 90 injection drug users (IDUs). TDR was reported following the WHO mutation list. The TDR rate in the whole cohort was 8.3 %, being the highest in MSM (9.1 %) and the lowest in IDUs (4.4 %). Over time, this rate decreased significantly (to 5.4 % in 2009-2011) since the period 2004-2006, when it peaked (10.7 %). Heterosexuals and IDUs showed similar trends, but in the 2009-2011 period, the TDR rate among MSM rebounded to 9.0 % (being absent among IDUs). TDR stabilized in the last years (2007-2011) for nucleoside reverse transcriptase inhibitors. The risk group also determined differences in the mutational profile, sex distribution, proportion of immigrants, and viral variants. In conclusion, the risk group caused different HIV sub-epidemics, determined by the patients' profiles. Despite the general decreasing trend in TDR, we observed a non-significant increase in TDR rate among MSM, a tendency that needs confirmation. Periodic TDR surveillance is important to prevent the widespread distribution of resistance, especially in MSM, given the growing HIV/AIDS epidemic in this high-risk population.

Surveillance of Transmitted HIV Drug Resistance in Antiretroviral-Naive Patients Aged less than 25 Years, in Bangkok, Thailand

Emergence of transmitted HIV drug resistance (TDR) is a concern after global scale-up of antiretroviral therapy (ART). World Health Organization had developed threshold survey method for surveillance of TDR in resource-limited countries. ART in Thailand has been scaling up for >10 years. To evaluate the current TDR in Thailand, a cross-sectional study was conducted among antiretroviral-naive HIV-infected patients aged <25 years who newly visited infectious disease clinic in a university hospital, in 2011. HIV genotypic-resistance test was performed. World Health Organization 2009 surveillance drug-resistance mutations were used to define TDR. Of 50 patients, the prevalence of TDR was 4%. Of 2 patients with TDR, 1 had K103N and the other had Y181C mutations. Transmitted HIV drug resistance is emerging in Thailand after a decade of rapid scale-up of ART. Interventions to prevent TDR at the population level are essentially needed in Thailand. Surveillance for TDR in Thailand has to be regularly performed.

Low abundance drug resistance variants in transmitted HIV drug resistance surveillance specimens identified using tagged pooled pyrosequencing

HIV drug resistance (DR) testing using Sanger sequencing (SS) is limited by the inability of the method to identify low abundance drug resistance variants. The application of tagged pooled pyrosequencing (TPP) for HIV DR surveillance is described and the results compared with SS. HIV(+) serum specimens were genotyped using both SS and TPP. Surveillance drug resistance mutations were identified using SS and TPP consensus reads at multiple mixed base identification thresholds (MBITs). Drug resistance patterns were highly concordant between SS and TPP when the MBIT was set at 20%. DR mutations were detected in 7.1% of the subjects, with 1.6% of individuals harboring resistance to NRTI, 3.3% NNRTI and 2.7% PI. Analyzing the TPP reads for each subject confirmed that drug resistance mutations with frequencies <20% were inconsistently detected by SS. Conversely, low abundance drug resistant variants were easily identified using TPP with mixed base identification threshold set at low value. In conclusion, at considerable savings when compared to commercial assays, TPP produces HIV DR profiles that are concordant with those from SS, furthermore, these same data can be used to identify low abundance drug resistant variants.

Increase in transmitted HIV drug resistance among persons undergoing genotypic resistance testing in Ontario, Canada, 2002-09

To characterize persons undergoing HIV genotypic resistance testing (GRT) while treatment naive and to estimate the prevalence of transmitted HIV drug resistance (TDR) among HIV-positive outpatients in Ontario, Canada. We analysed data from a multi-site cohort of persons receiving HIV care. Data were obtained from medical chart abstractions, interviews and record linkage with the Public Health Laboratories, Public Health Ontario. The analysis was restricted to 626 treatment-naive persons diagnosed in 2002-09. TDR mutations were identified using the calibrated population resistance tool. We used descriptive statistics and regression methods to characterize treatment-naive GRT test uptake and patterns of TDR. Overall, 53.2% (333/626) of participants had baseline GRT. The proportion increased with year of HIV diagnosis from 30.0% in 2002 to 82.6% in 2009 (P < 0.0001). Among those tested, 13.6% (CI 9.9-17.3%) had one or more drug resistance mutations, and 8.8% (CI 5.7-11.8%), 4.8% (CI 2.5-7.2%) and 2.7% (CI 1.0-4.5%) had mutations conferring resistance to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), respectively. TDR prevalence increased from 2002-07 to 2008-09 (adjusted OR 3.7, 95% CI 1.7-8.2), driven by a higher proportion with NRTI (18.2% versus 5.9%, P = 0.0009) and NNRTI mutations (11.7% versus 2.8%, P = 0.004) in the later time period. PI TDR remained unchanged. Baseline GRT increased dramatically since 2002, but remains below 100%. The prevalence of overall TDR tripled due to increases in NRTI and NNRTI mutations. These findings highlight the value of routine baseline GRT for TDR surveillance and patient care.

Short Communication: High Prevalence of Transmitted Antiretroviral Drug Resistance Among Newly HIV Type 1 Diagnosed Adults in Mombasa, Kenya

Abstract In view of the recent antiretroviral therapy (ART) scale-up in Kenya, surveillance of transmitted HIV drug resistance (TDR) is important. A cross-sectional survey was conducted among newly HIV-1 diagnosed, antiretroviral-naive adults in Mombasa, Kenya. Surveillance drug resistance mutations (SDRMs) were identified according to the 2009 WHO list. HIV-1 subtypes were determined using REGA and SCUEAL subtyping tools. Genotypic test results were obtained for 68 of 81 participants, and SDRMs were identified in 9 samples. Resistance to nonnucleoside reverse transcriptase inhibitors (K103N) occurred in five participants, yielding a TDR prevalence of 7.4% (95% confidence interval 2.4-16.3%). Frequencies of HIV-1 subtypes were A (70.6%), C (5.9%), D (2.9%), and unique recombinant forms (20.6%). The TDR prevalence found in this survey is higher than previously reported in different regions in Kenya. These findings justify increased vigilance with respect to TDR surveillance in African regions where ART programs are scaled-up in order to inform treatment guidelines.

Increase of Transmitted Drug Resistance among HIV-Infected Sub-Saharan Africans Residing in Spain in Contrast to the Native Population

BackgroundThe prevalence of transmitted HIV drug resistance (TDR) is stabilizing or decreasing in developed countries. However, this trend is not specifically evaluated among immigrants from regions without well-implemented antiretroviral strategies.MethodsTDR trends during 1996–2010 were analyzed among naïve HIV-infected patients in Spain, considering their origin and other factors. TDR mutations were defined according to the World Health Organization list.Results Pol sequence was available for 732 HIV-infected patients: 292 native Spanish, 226 sub-Saharan Africans (SSA), 114 Central-South Americans (CSA) and 100 from other regions. Global TDR prevalence was 9.7% (10.6% for Spanish, 8.4% for SSA and 7.9% for CSA). The highest prevalences were found for protease inhibitors (PI) in Spanish (3.1%), for non-nucleoside reverse transcriptase inhibitors (NNRTI) in SSA (6.5%) and for nucleoside reverse transcriptase inhibitors (NRTI) in both Spanish and SSA (6.5%). The global TDR rate decreased from 11.3% in 2004–2006 to 8.4% in 2007–2010. Characteristics related to a decreasing TDR trend in 2007-10 were Spanish and CSA origin, NRTI- and NNRTI-resistance, HIV-1 subtype B, male sex and infection through injection drug use. TDR remained stable for PI-resistance, in patients infected through sexual intercourse and in those carrying non-B variants. However, TDR increased among SSA and females. K103N was the predominant mutation in all groups and periods.ConclusionTDR prevalence tended to decrease among HIV-infected native Spanish and Central-South Americans, but it increased up to 13% in sub-Saharan immigrants in 2007–2010. These results highlight the importance of a specific TDR surveillance among immigrants to prevent future therapeutic failures, especially when administering NNRTIs.

Documented Prevalence of HIV Type 1 Antiretroviral Transmitted Drug Resistance in Ireland from 2004 to 2008

HIV-1-infected individuals with transmitted HIV drug resistance (TDR) begin antiretroviral therapy (ART) with a lower genetic barrier to resistance and a higher risk of both virological failure and of developing further resistance. TDR surveillance informs HIV-1 public health strategies and first line ART. TDR has not been studied nationally in an Irish population. This study includes all new HIV diagnoses from January 2004 to September 2008 from the National Virus Reference Laboratory, University College Dublin. HIV-1 protease and reverse transcriptase sequences were generated, and resistance mutations identified using the Siemens TRUGENE HIV-1 Genotyping System. Subtypes were determined using web-based genotyping tools. The study comprised 1579 patients. There were 305 new diagnoses in 2004 (173 male; 132 female), 298 in 2005 (175M; 123F), 321 in 2006 (197M; 124F), 297 in 2007 (184M; 113F), and 358 (235M; 123F) in 2008. HIV-1 RNA was sequenced from 158/305 patients in 2004, 199/298 in 2005, 225/321 in 2006, 203/297 in 2007, and 275/358 in 2008. The overall TDR rate was 6.3%, peaking in 2006 at 10.4% and declining to 5.3% in 2008. The majority of TDR was seen in Irish born individuals with HIV-1 subtype B infection. The TDR rate in Ireland is comparatively low. Thus, a health technology assessment is required to ascertain the most cost effective use of genotypic antiretroviral resistance testing (GART) in the future: the current approach of performing baseline GART on all new diagnoses, or perhaps a more targeted approach that focuses on patients commencing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART.