Prevalence Of Transmitted HIV Drug Resistance Research Articles

Transmitted HIV drug resistance among individuals with newly diagnosed HIV infection: a multicenter observational study

Fifteen years after the roll-out of antiretroviral treatment (ART) in China, there is limited information available on transmitted HIV drug resistance (TDR). This study aimed to characterize the epidemiology of TDR in China. We conducted a prospective cross-sectional observational study. We analyzed the demographic, clinical, and virological data of individuals with newly diagnosed HIV infection using data from the Beijing HIV laboratory network collected between 2001 and 2017. We did population-based sequencing of the pol gene on plasma specimens and identified TDR mutations using the WHO list for surveillance of TDR mutations. Data on TDR were available for 91% of the 10 115 individuals with newly diagnosed HIV infection tested, of whom 19.2% were from rural areas. The overall prevalence of TDR was 4.1% [95% confidence interval (CI): 3.7-4.5%], with a declining trend over the period 2001-2017. In the multivariable analysis, the risk of TDR differed significantly according to sex [odds ratio (OR) for women vs. men: 0.41, 95% CI: 0.22-0.69, P = 0.002]; infection type (OR for CRF07_BC vs. CRF01_AE: 0.24, 95% CI: 0.16-0.36, P < 0.001); and sampling period (OR for 2009-2012 vs. 2001-2008: 0.57, 95% CI: 0.41-0.79; P = 0.01), and was significantly higher among individuals from Hebei province than in those from Beijing (OR: 1.43, 95% CI: 1.05-1.96; P = 0.02). In China, the prevalence of TDR among individuals with newly diagnosed HIV infection is relatively low. Trends in TDR should be assessed in other countries with a high TDR burden.

Prevalence of pretreatment HIV drug resistance in Mwanza, Tanzania.

In a 2008-10 study, we found a pretreatment HIV drug resistance (PDR) prevalence of 18.2% in patients at Bugando Medical Centre (BMC) in Mwanza, Tanzania. To determine the prevalence of PDR and transmitted HIV drug resistance (TDR) in patients visiting the BMC from 2013 to 2015. Adult outpatients were sequentially enrolled into two groups, separated by whether they were initiating ART. Previous exposure to antiretroviral drugs, except for prevention of mother-to-child transmission, was an exclusion criterion. HIV pol sequences were analysed according to WHO guidelines for surveillance of PDR and TDR. Two hundred and thirty-five sequences were analysed (138 ART initiators, 97 non-initiators). The prevalence of PDR was 4.7% (95% CI 2.6%-8.2%) overall, 3.1% (95% CI 1.1%-8.7%) for non-initiators and 5.8% (95% CI 3.0%-11.0%) for ART initiators. PDR to NNRTIs and nucleoside or nucelotide reverse transcriptase inhibitors was found in 3.0% (95% CI 1.5%-6.0%) and 1.7% (95% CI 0.7%-4.3%) of patients, respectively. Resistance to PIs was not observed. The prevalence of TDR was 6.0% (95% CI 3.6%-9.8%). Prevalence of PDR significantly decreased compared with 2008-10 and was below the WHO-defined threshold for triggering a public health response. National and systematic surveillance is needed to inform Tanzania's public health strategy.

Evolution of transmitted HIV‐1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169-521 cells/μL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P=0.003): TDR to NRTIs from 9.9 to 2.9% (P=0.003) and TDR to NNRTIs from 5.1 to 3.7% (P=0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P<0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P<0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P=0.04) but not in non-B subtypes (from 6.1 to 5.8%; P=0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P<0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P=0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P=0.01), and earlier calendar year (per 1year more recent: AOR 0.95; 95% CI 0.91-0.99; P=0.02). The prevalence of HIV-1 TDR has declined during the last 10years in Italy.

Provincial and national prevalence estimates of transmitted HIV-1 drug resistance in South Africa measured using two WHO-recommended methods.

Sentinel surveillance of transmitted HIV drug resistance (TDR) among recently infected populations within a country was recommended by the World Health Organization from 2004 to 2015. Serum specimens collected as part of the 2010, 2011 and 2012 National Antenatal Sentinel HIV Prevalence Surveys were used to estimate provincial and national TDR prevalence in South Africa. Moderate (5-15%) levels of transmitted non-nucleoside reverse transcriptase inhibitor (NNRTI) drug class resistance were detected in three of five provinces surveyed in 2010 and 2011 (Eastern Cape, Free State and KwaZulu-Natal). Inclusion of all nine of South Africa's provinces in the 2012 survey enabled calculation of a national TDR point prevalence estimate: TDR to the NNRTI drug class was 5.4% (95% CI 3.7, 7.8%), with K103N and V106M being the most frequently detected mutations. TDR estimates for the nucleoside reverse transcriptase inhibitor (NRTI) drug class were 1.1% (95% CI 0.5, 2.4%) and 0.6% (95% CI 0.1, 1.6%) for protease inhibitors (PI). These data provide national TDR estimates for South Africa in 2012 and indicate that levels of TDR were low to moderate for the NNRTI drug class and low for NRTIs and PIs in the population surveyed.

Prevalence of HIV-1 transmitted drug resistance in recently infected, treatment-naïve persons in the Southwest of Iran, 2014-2015.

The emergence and transmission of drug resistant HIV mutants is a major concern, especially in resource-limited countries with expanding antiretroviral therapy. Studies have recently reported the prevalence of HIV-1 transmitted drug resistance (TDR) mutations in certain Iranian cities; however, no information is currently available about the level of TDR, as well as the nature of the circulating HIV-1 subtypes, in the Southwestern bordering province of Iran, Khuzestan. Herein, we used a WHO-recommended TDR survey method to classify the prevalence of TDR in indigenous people of Khuzestan province. For this purpose, between March 2014 and February 2015, blood samples were collected from 52 newly diagnosed, antiretroviral treatment-naïve, HIV-1 infected persons aged from 18 to 30 years. TDR mutations were determined by sequencing the protease (PR) and reverse transcriptase (RT) genes and interpreted using the WHO drug resistance mutations surveillance list. HIV-1 subtypes were characterized by sequencing the PR-RT, C2-V5, and p17 regions of the pol, env and gag genes, respectively. Two participants had non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, specifically K103N in one individual and K101EK/K103KN/G190AG in the other. No nucleoside reverse transcriptase inhibitor (NRTI) or major protease inhibitor (PI) mutations were identified. HIV-1 subtyping revealed that all participants were infected with HIV-1 CRF35_AD. According to the WHO sequential sampling method, the prevalence of HIV-1 TDR in the sampling area (Khuzestan province) was classified as moderate for NNRTIs and low for NRTIs and PIs. This is the first HIV-1 drug resistance threshold survey in the Khuzestan province of Iran and shows a predominance of NNRTI TDR mutations in this area.

Sensitive sentinel mutation screening reveals differential underestimation of transmitted HIV drug resistance among demographic groups.

To examine the association of majority and minority-level transmitted HIV drug resistance (TDR) among diverse demographic populations in the United States and assess what different mutations may infer about TDR risk and engagement in care. Used sensitive assays to screen 1070 deidentified convenience plasma specimens from United States national HIV surveillance conducted in 2009-2011 on newly diagnosed persons with no evidence of antiretroviral drug use. We applied validated allele-specific PCR for five HIV reverse transcriptase mutations as sentinel markers of TDR. The total and minority-level prevalence of TDR by demographic characteristics was compared. Sensitive screening identified 72% more TDR than conventional sequencing for the five mutations assessed (13.6 vs. 7.9%, P < 0.0001), with K65R having the greatest increase (0-1.7%). One-third of K65R was in persons who also had at least one of the other mutations screened. The total TDR prevalence among whites (16.4%) and blacks (14.9%) was significantly higher than that among Hispanics/Latinos (6.4%) (P = 0.005 and 0.013, respectively). TDR prevalence was highest (23.1%) in those 13-19 years (85% black). TDR prevalence among women (72% black) was nearly as high as among MSM (47% black) (14.3 vs. 15.1%, respectively). A significant proportion of TDR, primarily in older, white MSM, was undetected by conventional testing. The greatest underestimation was for rapid-decaying mutations typically associated with the source virus having recent exposure to antiretroviral therapy. However, total TDR prevalence was highest in the less than 20-year age group who were predominantly black, underscoring the importance of prevention efforts for at-risk youth.

Projecting the epidemiological effect, cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies.

The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from <5% to 5%-15% in the past decade. Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV-related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds.

Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis.

Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries. We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups. A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM. TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.

Prevalence and circulation patterns of variant, atypical and resistant HIV in Los Angeles County (2007-2009).

The prevalence of transmitted HIV drug resistance (TDR) in Los Angeles County remains unknown, due in part to the absence of reliable genotypic data. The specific objectives of this study are to estimate the prevalence of TDR, to describe the demographic characteristics associated with TDR and to investigate the distribution of HIV-1 subtypes among persons newly diagnosed with HIV in Los Angeles County. From 2007 through 2009, 1,414 sequences were obtained from 7,100 persons newly diagnosed with HIV through HIV resistance surveillance. Overall, 257 (18%) sequences had some genetic evidence of drug resistance. Of these, 122 (9%) exhibited evidence of resistance to non-nucleoside reverse transcriptase inhibitors, 121 (9%) to nucleoside reverse transcriptase inhibitors and 76 (5%) to protease inhibitors. Subtype B was dominant (97%), followed by subtypes C (1.2%), CRF01_AE (0.8%), CRF02_AG (0.4%), A (0.3%), and F (0.1%). With a TDR prevalence of 18%, Los Angeles County ranks high compared with other jurisdictions across the nation. The prevalence of TDR in recent (19%) and long-standing (17%) HIV cases were similar, thus providing additional support for the notion that TDR-associated mutations may persist well beyond the period of recent infection. HIV-1 CRF01_AE, observed historically in central Africa and Asia, was observed to be circulating among men who have sex with men and heterosexuals in Los Angeles County. These findings underscore the need for continued and expanded HIV resistance surveillance to inform healthcare providers, policy makers and at-risk populations of emerging trends in HIV drug resistance.

Prevalence of Transmitted HIV-1 Drug Resistance (TDR) Associated Mutations and Predicted Drug Sensitivity in Newly Diagnosed HIV-1 Patient Cohort in a Western New York, 2005-2011

HIV-1 drug resistance associated mutations can be transmitted to persons who are antiretroviral-naive, called Transmitted Drug Resistance (TDR). TDR has the potential to compromise first-line anti-retroviral therapy (ART) in HIV patients and limit the antiretroviral regimens options, which has become an important public health problem. TDR surveillance is an important strategy to monitor the emergence of genetic. TDR has been reported in the United States for many years. Current antiretroviral treatment guidelines recommend drug resistance testing after diagnosis. We did a retrospective analysis of the genotype database of ART-naive patients from our immunodeficiency clinics at the Erie County Medical Center (ECMC) in Buffalo, New York, United States from 2005 to 2011. The prevalence of TDR in the ECMC-US cohort is still high 13.3%. The drug susceptibility is significantly reduced in 10.9% patients. The mutations were mostly “old” drug (such as AZT, D4T, EFV, NVP, SQV/r) related, while most of the “new” drugs (such as TDF, RPV, DRV/r) maintained sensitivity. The introduction of new second, third generation drugs in recent years has not brought down the prevalence of TDR significantly. The TDR prevalence rates in the United States are indicative of the fact that drug resistant mutations were generated before or at the beginning of ART and transmitted down from one generation to the other in ART naive patients, emphasizing that additional management strategies are needed to diagnose HIV infected patients earlier and to effectively treat them timely to further reduce TDR.

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.

Transmitted HIV drug resistance in treatment‐naive Romanian patients

Transmitted HIV drug resistance (TDR) remains an important concern for individuals unexposed to antiretroviral treatment. Data on the prevalence of TDR, available mainly for HIV-1 subtype B, are now also emerging for other subtypes. In Romania, a steady predominance of subtype F was reported among both long-term survivor children and newly infected adults. The pol gene of 61 drug-naïve patients infected with HIV, diagnosed between 1997 and 2011 was sequenced in order to analyze the prevalence of primary resistance mutations and to correlate these with the infecting genotype. Only 5/61 specimens were classified as infected recently using the BED-Capture Enzyme Immunoassay. Subtype F1 was prevalent (80.3%), however, other HIV-1 clades are increasingly identified, especially in the group of subjects infected recently. An HIV transmission cluster, associated to injecting drug use was identified by phylogenetic analysis. The overall prevalence of TDR was 14.75%, mainly associated with NRTI resistance (13.11%), TAMs and M184V being the most common mutations. A declining trend of TDR was recorded from 26.08% in 1997-2004 to 7.89% in 2005-2011. No primary resistance was identified among recent seroconvertors. All HIV-1 strains had minor mutations in the protease and RT genes, often detected at polymorphic positions. The declining rates of TDR might be related to the high efficacy of HAART and to the increasing number of treated patients with virological success who have a low risk of transmission. The recent increase of HIV-1 infections which involve other subtypes impose a continuous surveillance of the genetic composition of the epidemic.

HIV drug resistance surveillance in low‐ and middle‐income countries: 2004 to 2010

BackgroundAt the end of 2011, over 8 million people were receiving antiretroviral therapy (ART) in low- and middle-income countries (LMIC), a 26-fold increase from 2003. Some degree of HIV drug resistance (HIVDR) will emerge among populations on combination ART even when high levels of adherence are achieved. In 2004, the World Health Organization (WHO) initiated global HIVDR surveillance to monitor emergence and transmission of HIVDR in countries scaling-up ART.MethodsWHO HIVDR surveillance strategy was designed to inform public health decision-making regarding choice of ART and to identify ART programme factors which could be adjusted to minimize HIVDR emergence. The strategy includes (1) surveillance of transmitted HIVDR (TDR) in recently infected populations, (2) surveillance of acquired HIVDR (ADR) in populations on ART and (3) monitoring of early warning indicators (EWI) of HIVDR which are ART programme factors favouring HIVDR emergence. Surveys used standardized protocols. Epidemiological and sequence data were quality assured.Results TDR: Eighty-two surveys were conducted in 30 countries in 2004 to 2010, assessing 3588 recently infected individuals. Pooled analysis indicates an overall prevalence of 3.1% TDR to at least one drug class, 1.6% to non-nucleoside reverse transcriptase inhibitor (NNRTI), 1.3% to nucleoside reverse transcriptase inhibitor (NRTI) and 0.7% to protease inhibitor (PI). Levels of NNRTI resistance, particularly in the areas surveyed in Africa, increased over time, reaching 3.4% (95% CI=1.8 to 5.2%) in 2009. Greater ART coverage was associated, though modestly, with increased prevalence of TDR to NNRTI (P-value adjusted for region=0.039). ADR: Thirty-six ADR surveys assessing 6370 people in 12 LMIC were conducted in 2007 to 2010. HIVDR prevalence to any drug among those initiating ART ranged from 4.8% (95% CI=3.8 to 6.0%) in 2007 to 6.8% (95% CI=4.8 to 9.0%) in 2010. Ninety per cent of patients alive and on therapy at 12 months achieved viral load <1000 c/mL. Among people with virological failure, 72% had HIVDR to at least one drug. EWI: EWIs were monitored at 2017 clinics in 50 countries assessing 131,686 people since 2004. Overall, 75% of clinics met the target of 100% of patients receiving appropriate ART; 69% of clinics met the <20% target for lost to follow-up at 12 months; and only 65% of clinics provided a continuous supply of ART during a 12-month period.ConclusionExpansion of ART in LMIC has resulted in an overall increase in HIVDR, particularly to NNRTI in Africa. EWIs reveal important gaps in service delivery and programme performance. While these data call for continued and improved scale up of surveillance, they also suggest that resistance is under control in the areas surveyed, and the majority of patients initiating or switching therapy are likely to respond to currently available first- and second-line therapy.

Low Prevalence of Transmitted HIV Type 1 Drug Resistance Among Antiretroviral-Naive Adults in a Rural HIV Clinic in Kenya

Low levels of HIV-1 transmitted drug resistance (TDR) have previously been reported from many parts of sub-Saharan Africa (sSA). However, recent data, mostly from urban settings, suggest an increase in the prevalence of HIV-1 TDR. Our objective was to determine the prevalence of TDR mutations among HIV-1-infected, antiretroviral (ARV)-naive adults enrolling for care in a rural HIV clinic in Kenya. Two cross-sectional studies were carried out between July 2008 and June 2010. Plasma samples from ARV-naive adults (>15 years old) at the time of registering for care after HIV diagnosis and before starting ARVs were used. A portion of the pol subgenomic region of the virus containing the protease and part of the reverse transcriptase genes was amplified and sequenced. TDR mutations were identified and interpreted using the Stanford HIV drug resistance database and the WHO list for surveillance of drug resistance strains. Overall, samples from 182 ARV-naive adults [mean age (95% CI): 34.9 (33.3-36.4) years] were successfully amplified and sequenced. Two TDR mutations to nucleoside reverse transcriptase inhibitors [n=1 (T215D)] and protease inhibitors [n=1 (M46L)] were identified, giving an overall TDR prevalence of 1.1% (95% CI: 0.1-3.9). Despite reports of an increase in the prevalence of HIV-1 TDR in some urban settings in sSA, we report a prevalence of HIV-1 TDR of less than 5% at a rural HIV clinic in coastal Kenya. Continued broader surveillance is needed to monitor the extent of TDR in sSA.

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.

Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance

BackgroundEstimates of the prevalence of transmitted HIV drug resistance (TDR) in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART). Much of the debate over reliability of estimates of the prevalence of TDR has focused on whether the sample population is representative. However estimates of the prevalence of TDR will also be distorted if some ART-experienced patients are misclassified as ART-naïve.MethodsThe impact of misclassification bias on the rate of TDR was examined. We developed methods to obtain adjusted estimates of the prevalence of TDR for different misclassification rates, and conducted sensitivity analyses of trends in the prevalence of TDR over time using data from the UK HIV Drug Resistance Database. Logistic regression was used to examine trends in the prevalence of TDR over time.ResultsThe observed rate of TDR was higher than true TDR when misclassification was present and increased as the proportion of misclassification increased. As the number of naïve patients with a resistance test relative to the number of experienced patients with a test increased, the difference between true and observed TDR decreased. The observed prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR increased by 1.10 (95% CI 1.02, 1.19, p(linear trend) = 0.02) per year 1997-2002) before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87, 0.94, p(linear trend) < 0.001) per year 2002-2007. Trends in adjusted TDR were altered as the misclassification rate increased; the significant downward trend between 2002-2007 was lost when the misclassification increased to over 4%.ConclusionThe effect of misclassification of ART on estimates of the prevalence of TDR may be appreciable, and depends on the number of naïve tests relative to the number of experienced tests. Researchers can examine the effect of ART misclassification on their estimates of the prevalence of TDR if such a bias is suspected.

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.

Transmitted antiretroviral drug resistance among newly HIV-1 diagnosed young individuals in Kampala

To assess the emergence of transmitted HIV-1 drug resistance (TDR) in Kampala, Uganda, 10 years after the scale-up of antiretroviral treatment (ART) and to compare with a previous survey among antenatal clinic attendees in 2007 (reporting 0% TDR). A cross-sectional survey was conducted among newly HIV-1 diagnosed, antiretroviral-naive young adults attending two large voluntary counseling and testing centers within the geographic area of Kampala. Proxy criteria for recent HIV-1 infection were used as defined by the WHO. Population sequencing of the pol gene was performed on plasma samples with HIV-1 RNA at least 1000 copies/ml. Surveillance drug resistance mutations (SDRMs) were identified according to the 2009 WHO list for surveillance of TDR. HIV-1 subtypes were designated using maximum likelihood phylogenetic reconstruction. : Genotypic test results were obtained for 70 of 77 (90.9%) participants. SDRMs were identified in six samples yielding a prevalence of TDR of 8.6% (95% confidence interval 3.2-17.7%). Two had SDRMs to nucleoside reverse-transcriptase inhibitors (D67G and L210W), three had SDRMs to nonnucleoside reverse transcriptase inhibitors (G190A, G190S, and K101E), and one had SDRMs to protease inhibitors (N88D). Frequencies of HIV-1 subtypes were A (36/70, 51.4%), C ( two of 70; 2.9%), D (23/70, 32.9%), and unique recombinant forms (nine of 70, 12.9%). This repeated survey suggests an increase in TDR in Kampala, compared with a previous survey. This finding justifies increased vigilance with respect to surveillance of TDR in areas in Africa where ART programs are rolled-out.