Prevalence Of HIV Drug Resistance Research Articles

High level of pre-treatment and acquired HIV drug resistance in Honduras: a nationally representative survey, 2016-17.

Pre-treatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in low-/middle-income countries during the last decade. To estimate the prevalence of pre-treatment HIVDR and acquired HIVDR among persons living with HIV (PLHIV) on ART for 12 ± 3 months (ADR12) and ≥48 months (ADR48) in Honduras. A nationwide cross-sectional survey with a two-stage cluster sampling was conducted from October 2016 to November 2017. Twenty-two of 54 total ART clinics representing >90% of the national cohort of adults on ART were included. HIVDR was assessed for protease and reverse transcriptase Sanger sequences using the Stanford HIVdb tool. A total of 729 PLHIV were enrolled; 26.3% (95% CI 20.1%-33.5%) ART initiators reported prior exposure to antiretrovirals. Pre-treatment HIVDR prevalence was 26.9% (95% CI 20.2%-34.9%) to any antiretroviral and 25.9% (19.2%-33.9%) to NNRTIs. NNRTI pre-treatment HIVDR was higher in ART initiators with prior exposure to antiretrovirals (P = 0.001). Viral load (VL) suppression rate was 89.7% (85.1%-93.0%) in ADR12 and 67.9% (61.7%-73.6%) in ADR48. ADR12 to any drug among PLHIV with VL ≥1000 copies/mL was 86.1% (48.9%-97.6%); 67.1% (37.4%-87.5%) had HIVDR to both NNRTIs and NRTIs, and 3.8% (0.5%-25.2%) to PIs. ADR48 was 92.0% (86.8%-95.3%) to any drug; 78.1% (66.6%-86.5%) to both NNRTIs and NRTIs, and 7.3% (1.8%-25.1%) to PIs. The high prevalence of NNRTI pre-treatment HIVDR observed in Honduras warrants consideration of non-NNRTI-based first-line regimens for ART initiation. Programmatic improvements in HIVDR monitoring and adherence support may also be considered.

HIV-1 Drug Resistance, Distribution of Subtypes, and Drug Resistance-Associated Mutations in Virologic Failure Individuals in Chengdu, Southwest China, 2014-2016.

The National Free Antiretroviral Therapy (ART) Program in China has initiated to provide ART to HIV-1 patients, which has acted as an efficient method to suppress viral replication and helps prevent onward transmissions. But the problems of HIV drug resistance (HIVDR) may also come along. There is little data on the prevalence of HIVDR in Chengdu, where the number of HIV/AIDS patients ranks first among provincial capitals. Therefore, epidemiological surveillance was conducted in this area. From 2014 to 2016, HIV/AIDS patients (15 years and older) who had received first-line ART for at least six months were enrolled. Demographic, behavioral information and medical history were recorded, and blood samples were collected for viral loads and immune cell count analyses. HIV-1 pol was obtained for HIV-1 subtypes and drug resistance-associated mutations (DRMs) among virologic failure patients. A total of 13,782 individuals were enrolled, and 481 samples were sequenced for subtypes and drug resistance analysis. Six subtypes were identified, among which CRF01_AE (54.3%) and CRF07_BC (41.6%) were the dominant subtypes, and CRF55_01B (0.4%) was detected in Chengdu for the first time. The prevalence of HIVDR in treatment-experienced patients was 1.8%, with 1.2% to nucleoside reverse transcriptase inhibitors (NRTIs), 1.7% to non-NRTIs (NNRTIs), and 0.14% to protease inhibitors (PIs). The leading DRMs observed in the study were M184I/V (59.59%) against NRTIs and K103N (37.55%) against NNRTIs. This study focused on the HIVDR surveillance among patients receiving treatment in Chengdu. The overall prevalence of HIVDR was relatively low among treated patients. These findings were believed to be contributed to an understanding of HIV-1 subtypes, HIVDR prevalence, and DRMs in Chengdu and thereby optimizing clinical management, prevention, and control of HIV.

OLA-Simple: A software-guided HIV-1 drug resistance test for low-resource laboratories.

BackgroundHIV drug resistance (HIVDR) testing can assist clinicians in selecting treatments. However, high complexity and cost of genotyping assays limit routine testing in settings where HIVDR prevalence has reached high levels.MethodsThe oligonucleotide ligation assay (OLA)-Simple kit was developed for detection of HIVDR against first-line non-nucleoside/nucleoside reverse transcriptase inhibitors and validated on 672 codons (168 specimens) from subtypes A, B, C, D, and AE. The kit uses dry reagents to facilitate assay setup, lateral flow devices for visual HIVDR detections, and in-house software with an interface for guiding users and analyzing results.FindingsHIVDR analysis of specimens by OLA-Simple compared to Sanger sequencing revealed 99.6 ± 0.3% specificity and 98.2 ± 0.9% sensitivity, and compared to high-sensitivity assays, 99.6 ± 0.6% specificity and 86.2 ± 2.5% sensitivity, with 2.6 ± 0.9% indeterminate results. OLA-Simple was performed more rapidly compared to Sanger sequencing (<4 h vs. 35–72 h). Forty-one untrained volunteers blindly tested two specimens each with 96.8 ± 0.8% accuracy.InterpretationOLA-Simple compares favorably with HIVDR genotyping by Sanger and sensitive comparators. Instructional software enabled inexperienced, first-time users to perform the assay with high accuracy. The reduced complexity, cost, and training requirements of OLA-Simple could improve access to HIVDR testing in low-resource settings and potentially allow same-day selection of appropriate antiretroviral therapy.FundUSA National Institutes of Health R01; the Clinical and Retrovirology Research Core and the Molecular Profiling and Computational Biology Core of the UW CFAR; Seattle Children's Research Institute; UW Holloman Innovation Challenge Award; Pilcher Faculty Fellowship.

HIV Drug Resistance among Patients Failing Therapy at a Tertiary Center in Oman: A Case Record Review.

ObjectivesWe sought to estimate the prevalence of HIV drug resistance and describe the common HIV genetic mutations in patients failing antiretroviral therapy (ART). We also investigated the impact of HIV resistance tests results on patients’ management.MethodsWe conducted a retrospective record review for all HIV genotypic resistance tests requested at the HIV clinic of a tertiary HIV center in Muscat, Oman, from April 2011 to May 2017.ResultsA total of 98 genotypic resistance tests for 84 patients failing ART were analyzed; 82 tests for 69 patients (83.7%, 95% confidence interval: 76.4–91.0) showed resistance to at least one ART drug. M184V/I, K103N/S, and G190A/S/E were the most common mutations detected. Among the tests with a resistant virus, 78.0% were followed by switching ART based on the resistance test profile resulting in virus load suppression after six months in 60.9% of the cases.ConclusionsHIV drug resistance is very common among HIV patients failing ART in Oman, and should be considered in those patients. Switching ART treatment based on the resistance test result leads to a good virological response in adherent patients.

Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4\u20138\u2009weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011\u201312 and 2012\u201313

BackgroundSouth Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts.MethodsThree nationally representative surveys were conducted in 2010, 2011–12 and 2012–13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4–8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3.ResultsOverall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45–58%]) of HIV PCR positive infants, 37% (95% CI [28–47%]) in 2010, 64% (95% CI [53–74%]) in 2011 and 63% (95% CI [47–77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance.ConclusionsThese data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

PREVALENCE AND STRUCTURE OF HIV-1 DRUG RESISTANCE AMONG TREATMENT NAÏVE PATIENTS SINCE THE INTRODUCTION OF ANTIRETROVIRAL THERAPY IN THE RUSSIAN FEDERATION

Aim:to analyze the prevalence, structure of drug resistance and drug resistance mutations in the protease and reverse transcriptase genes of HIV-1 among treatment naïve patients.Materials and methods.We analyzed protease and reverse transcriptase sequences from 1560 treatment naïve HIV-infected patients from all Federal Districts of the Russian Federation with the first positive immune blot during 1998–2017. Sequences were analyzed for the presence of drug resistance mutations and predicted drug resistance to antiretroviral drugs using two algorithms — Stanford HIVDR Database (HIVdb) and the 2009 SDRM list (CPR).Results.The prevalence of drug resistance mutations was 11,1%. More often the prevalence of drug resistance was found for non-nucleoside reverse transcriptase inhibitor drugs (rilpivirine, nevirapine, efavirenz). The prevalence of transmitted drug resistance associated with mutations from the SDRM list was 5,3%, which is classified by the WHO as a moderate level. However, it should be noted that since the large-scale use of antiretroviral drugs in the Russian Federation, there has been a trend towards a gradual increase in the level of the transmitted drug resistance, and in 2016 it has already reached 6,1%.Conclusion.The results demonstrate the need for regular surveillance of the prevalence of HIV drug resistance to antiretroviral drugs among treatment naïve patients in the Russian Federation.

Prevalence of drug resistance mutations among ART-naive and -experienced HIV-infected patients in Sierra Leone.

ObjectivesThe aim of this study was to assess the prevalence of HIV drug resistance (HIVDR) in HIV-infected ART-naive and -experienced patients in Sierra Leone.Patients and methodsWe conducted a cross-sectional study of HIV-positive adults aged ≥18 years at Connaught Hospital in Freetown, Sierra Leone in November 2017. Sequencing was performed in the reverse transcriptase, protease and integrase regions, and interpreted using the Stanford HIVDR database and WHO 2009 mutation list.ResultsTwo hundred and fifteen HIV-infected patients were included (64 ART naive and 151 ART experienced). The majority (66%) were female, the median age was 36 years and the median ART exposure was 48 months. The majority (83%) were infected with HIV-1 subtype CRF02_AG. In the ART-naive group, the pretreatment drug resistance (PDR) prevalence was 36.7% (14.2% to NRTIs and 22.4% to NNRTIs). The most prevalent PDR mutations were K103N (14.3%), M184V (8.2%) and Y181C (4.1%). In the ART-experienced group, 64.4% harboured resistance-associated mutations (RAMs) and the overall prevalence of RAMs to NRTIs and NNRTIs was 85.2% (52/61) and 96.7% (59/61), respectively. The most prevalent RAMs were K103N (40.7%), M184V (28.8%), D67N (15.3%) and T215I/F/Y (15.3%). Based on the genotypic susceptibility score estimates, 22.4% of ART-naive patients and 56% of ART-experienced patients were not susceptible to first-line ART used in Sierra Leone.ConclusionsA high prevalence of circulating NRTI- and NNRTI-resistant variants was observed in ART-naive and -experienced HIV-1-infected patients in Sierra Leone. This necessitates the implementation of HIVDR surveillance programmes to inform national ART guidelines for the treatment and monitoring of HIV-infected patients in Sierra Leone.

Prevalence of HIV-1 Drug Resistance among Patients with Antiretroviral Therapy Failure in Sichuan, China, 2010-2016.

Antiretroviral therapy (ART) has been introduced recently and has significantly impacted morbidity and mortality, but can also engender drug resistance. To identify the prevalence of HIV-1 drug resistance (HIVDR) among patients with antiretroviral therapy failure in Sichuan during the period from 2010 to 2016, we carried out a longitudinal study in Sichuan, a province with the highest HIV/AIDS prevalence in China. The data and blood samples were collected from HIV/AIDS patients who received ART for more than half a year. Overall 5,512 sequences were completed from 7,059 ART-failure patients, and 2,499 individuals were identified as drug resistant. Among those with HIVDR mutations identified, 25.37% were against non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.60% was against nucleoside reverse transcriptase inhibitors (NRTIs). NRTI-resistant drugs were mainly lamivudine (3TC) (57.77%) and emtricitabine (FTC), while NNRTI-resistant drugs were mainly nevirapine (NVP) (91.13%) and efavirenz (EFV) (72.81%). The most common recombination subtypes of HIV-1 in sequenced samples were CRF07_BC (circulating recombinant form, CRF) (41.42%), followed by CRF01_AE (40.77%). Moreover, drug resistance rate increased with the prolongation of treatment time (χ2 = 14.758, P < 0.05). The overall prevalence of acquired drug resistance in HIV-1 infected patients in Sichuan was 5.47%, which has remained relatively stable from 2010 to 2016. HIV-1 CRF01_AE and CRF07_BC subtypes were the main epidemic strains, and the possibility of resistance was higher in CRF01_AE subtypes. The current study highlights the importance of acquired drug resistance surveillance over a long period.

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance. Prospective clinical cohort of HIV-infected patients at the University of North Carolina. Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016. A total of 3682 patients contributed 23 169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes. Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently.

Viral load suppression and acquired HIV drug resistance in adults receiving antiretroviral therapy in Viet Nam: results from a nationally representative survey.

ObjectiveThe purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method.MethodsThe survey was conducted between May and August 2014 using a two-stage cluster design. Sixteen ART clinics were selected using probability proportional to proxy size sampling, and patients receiving ART for at least 36 months were consecutively enrolled. Epidemiological information and blood specimens were collected for HIV-1 VL and HIVDR testing; HIVDR was defined by the Stanford University HIVDR algorithm.ResultsOverall, 365 eligible individuals were recruited with a mean age of 38.2 years; 68.4% were men. The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0–81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. Of the 365 individuals, 345 (95.1%, 95% CI: 92.3–96.9%) had VL below 1000 copies/mL and 19 (4.6%, 95% CI: 2.8-–7.5) had HIVDR mutations.DiscussionOur nationally representative survey found a high level of VL suppression and a low prevalence of HIVDR among individuals who received ART for at least 36 months in Viet Nam. Continued surveillance for HIVDR is important for evaluating and improving HIV programs.

Genotypic Characterization of Human Immunodeficiency Virus Type 1 Prevalent in Kepulauan Riau, Indonesia.

Kepulauan Riau is a famous tourist destination in Indonesia. The epidemic of human immunodeficiency virus type 1 (HIV-1) infection is gradually increasing in this region. We collected peripheral blood samples from 62 antiretroviral therapy-experienced individuals. The amplification of viral genomic fragments, HIV-1 subtyping, and the detection of HIV drug resistance (HIVDR) were performed. Viral subtyping revealed that the most prevalent HIV-1 subtype/circulating recombinant form (CRF) was CRF01_AE (55.6%), followed by recombinants between CRF01_AE and subtype B (17.8%) and then subtype B (15.6%). Recombinants containing CRF02_AG gene fragments were also detected (11.1%). Regarding HIVDR, no drug resistance-associated major mutations were found in pol genes encoding protease, although minor mutations were frequently detected. Furthermore, major mutations, including M184V (2.2%) and Y188L (2.2%), were identified in the viral pol gene encoding reverse transcriptase derived from a study participant, suggesting that the prevalence of HIVDR is low in the region.

Antiretroviral Resistance in HIV/AIDS Patients

The higher prevalence of HIV drug resistance was observed in areas with greater ART coverage. The HIV resistance-associated mutations occur when people have inadequate levels of antiretroviral drugs as well as inadequate potency, inadequate adherence, and preexisting resistance. The degree to drug cross-resistance is observed depends on the specific mutations and number of mutation accumulation. In the Southeast Asia region, the challenging of people with treatment failure is the availability and accessibility to subsequent new antiretroviral drugs to construct he second and salvage regimen. Genotypic resistance testing is a useful tool because it can identify the existing drug resistance-associated mutations under the selective drug pressure. Thus, understanding the basic interpretation of HIV drug resistance- associated mutation is useful in guiding clinical decisions for treatment-experienced people living with HIV.

High Prevalence of HIV Drug Resistance Among Newly Diagnosed Infants Aged

WHO recommends protease-inhibitor-based first-line regimen in infants because of risk of drug resistance from failed prophylaxis used in prevention of mother-to-child transmission (PMTCT). However, cost and logistics impede implementation in sub-Saharan Africa, and >75% of children still receive nonnucleoside reverse transcriptase inhibitor-based regimen (NNRTI) used in PMTCT. We assessed the national pretreatment drug resistance prevalence of HIV-infected children aged <18 months in Nigeria, using WHO-recommended HIV drug resistance surveillance protocol. We used remnant dried blood spots collected between June 2014 and July 2015 from 15 early infant diagnosis facilities spread across all the 6 geopolitical regions of Nigeria. Sampling was through a probability proportional-to-size approach. HIV drug resistance was determined by population-based sequencing. Overall, in 48% of infants (205 of 430) drug resistance mutations (DRM) were detected, conferring resistance to predominantly NNRTIs (45%). NRTI and multiclass NRTI/NNRTI resistance were present at 22% and 20%, respectively, while resistance to protease inhibitors was at 2%. Among 204 infants with exposure to drugs for PMTCT, 57% had DRMs, conferring NNRTI resistance in 54% and multiclass NRTI/NNRTI resistance in 29%. DRMs were also detected in 34% of 132 PMTCT unexposed infants. A high frequency of PDR, mainly NNRTI-associated, was observed in a nationwide surveillance among newly diagnosed HIV-infected children in Nigeria. PDR prevalence was equally high in PMTCT-unexposed infants. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected young children regardless of PMTCT history and underscore the need to accelerate implementation of the newly disseminated guideline in Nigeria.

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations

New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations

HIV-1 viraemia and drug resistance amongst female sex workers in Soweto, South Africa: A cross sectional study.

BackgroundHIV drug resistance (HIVDR) poses a threat to future antiretroviral therapy success. Monitoring HIVDR patterns is of particular importance in populations such as sex workers (SWs), where documented HIV prevalence is between 34–89%, and in countries with limited therapeutic options. Currently in South Africa, there is a dearth in evidence and no ongoing surveillance of HIVDR amongst sex work populations. This study aims to describe the prevalence of HIVDR amongst a sample of female sex workers (FSWs) from Soweto, South Africa.MethodologyA cross-sectional, respondent driven sampling (RDS) recruitment methodology was used to enrol FSWs based in Soweto. Participants were tested for HIV and undertook a survey that included HIV knowledge and treatment status. Whole blood specimens were collected from HIV positive FSWs to measure for CD4 counts, viral load (VL) and perform HIVDR genotyping. Frequencies were determined for categorical variables and medians and interquartile ranges (IQR) for the continuous.ResultsOf the 508 enrolled participants, 55% (n = 280) were HIV positive and of median age 32 (IQR: 20–51) years. Among the HIV positive, 51.8% (132/269) were defined as virologically suppressed (VL < 400 copies/ml). Of the 119 individuals with unsuppressed viral loads who were successfully genotyped for resistance testing 37.8% (45/119) had detectable drug resistance. In this group, HIVDR mutations were found amongst 73.7% (14/19) of individuals on treatment, 27.4% (26/95) of individuals who were treatment naïve, and 100% (5/5) of defaulters. One phylogenetic cluster was found amongst treatment naïve FSWs. The K103N mutation was detected most commonly in 68.9% (31/45) individuals with HIVDR mutations, with 20/26 (76.9%) of treatment naïve FSW with detectable resistance having this mutation. The M184V mutation was found in both FSWs on treatment (12/14, 85.7%) and those defaulting (1/5, 20.0%).DiscussionMore than one third (45/119) of the genotyped sample had HIVDR, with resistance to the NNRTI class being the most common. Almost half of HIV positive FSWs had unsuppressed viral loads, increasing the likelihood for onward transmission of HIV. Disturbingly, more than 1:4 treatment naïve women with unsuppressed viral loads had HIVDR suggesting that possible sexual transmission of drug resistance is occurring in this high-risk population. Given the high burden of HIVDR in a population with a high background prevalence of HIV, it is imperative that routine monitoring of HIVDR be implemented. Understanding transmission dynamics of HIVDR in FSW and its impact on treatment success should be urgently elucidated.

Cost-effectiveness of public-health policy options in the presence of pretreatment NNRTI drug resistance in sub-Saharan Africa: a modelling study

SummaryBackgroundThere is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high.MethodsThe HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year.FindingsA transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost.InterpretationA future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance.FundingBill & Melinda Gates Foundation, World Health Organization.

Moderate Levels of Pretreatment HIV Drug Resistance — Zimbabwe, April–July 2015

BackgroundThe World Health Organization (WHO) HIV Drug Resistance (HIVDR) report 2012 demonstrated that the levels of HIVDR to first-line antiretroviral therapy (ART) are increasing. This finding threatens to reverse a decade of gains in HIV/AIDS epidemic control. The WHO Global Action Plan for HIVDR emphasizes strengthening surveillance of drug resistance through the implementation of national cross-sectional surveys. We conducted such survey to determine the prevalence of HIVDR among ART-naive patients in Zimbabwe and to describe the profile of the surveillance drug resistance mutations (SDRM) encountered in the country.MethodsA prospective, nationally representative, cross-sectional survey was conducted in 35 clinical sites selected using two stage probability proportional to size sampling. Patients were enrolled during April–July 2015. Specimens were sent for genotyping to CDC Atlanta. SDRM were interpreted using Stanford HIV Drug Resistance Database classification.ResultsA total of 361 subjects were surveyed. Most participants were female (60.3%) and the median age was 35.8 years. Thirty-four out of 361subjects presented with ≥1 SDRM (9.4%, 95% confidence interval: 6.8–12.8%) prior to initiation antiretroviral therapy (ART). Non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations were the most commonly detected mutation (n = 30). Only two patients presented with a nucleoside reverse transcriptase inhibitor mutation and one patient presented with a protease inhibitor mutation. In two patients, ≥3 SDRMs were detected, which may suggest they were not truly ART-naïve.ConclusionThis study provides national estimates of HIVDR in a high burden country with broad access to ART and provides valuable inisight on the state of HIVDR in such setting. Zimbabwe has reached moderate levels of HIVDR in ART-naive patients, as specified by the WHO classification. These levels may impact the ability to achieve viral suppression in a significant number of patients initiating standard ART regimens in Zimbabwe, where NNRTI-based regimens are used as the first line. The use of drugs with high resistance barrier, such as dolutegravir, may improve the care of patients in the developing world, where individualized pretreatment genotype is not feasible.Disclosures All authors: No reported disclosures.

Survey of HIV-1 drug resistance threshold in Shandong Province in 2013-2015

Objective: To survey the prevalence of drug resistant HIV-1 in Shandong province in 2013-2015. Methods: WHO truncated sequential sampling technique was adopted by using 77 and 53 samples of newly diagnosed as HIV-1 positive and aged 16-25 years in Shandong province in 2013 and 2015. RNA was prepared and HIV-1 pol region was amplified by RT-PCR and nested PCR. Pol genetic mutation associated with drug resistance was analyzed. Results: The success rates for sequence acquisition of the survey were 100% (77/77) and 94% (50/53) in 2013 and 2015, and the main subtype was CRF01_AE. A total of 2 surveillance drug-resistance mutation(SDRMs) and 3 SDRMs were found by analyzing the 47 sequences each year, sampled in 2013 and 2015, indicating that the prevalence of drug resistant HIV-1 stains was low in 2013, and moderate in 2015. A total of 5 individuals with drug resistant HIV-1 stains found in this study were mainly infected by homosexual transmission (3 cases), and the other two samples were different: one was infected by heterosexual transmission, the other was infected by IDU. The subtype was CRF01_AE (2 cases) , CRF07_BC (2 cases) and B (1 case) . SDRMs for protease inhibitor (PIs), nucleotide HIV-reverse transcriptase inhibitor (NRTIs) and non-NRTI (NNRTIs) were all found in the individuals with drug resistant HIV-1 stains. Conclusion: CRF01_AE were the main HIV-1 subtypes of recently reported HIV-infected individuals in Shandong province, and the HIV-1 drug resistant strains transmission was catalogued as at low and moderate prevalence level in 2013 and 2015.

Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003–2015: Transmitted drug resistance is due to onward transmissions

BackgroundThe prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. MethodsHIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003–30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. ResultsThe proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. ConclusionsThe TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

Prevalence of HIV-1 drug resistance in treated patients with viral load >50copies/mL: a 2014 French nationwide study.

Surveillance of HIV-1 resistance in treated patients with a detectable viral load (VL) is important to monitor, in order to assess the risk of spread of resistant viruses and to determine the proportion of patients who need new antiretroviral drugs with minimal cross-resistance. The HIV-1 protease and reverse transcriptase (RT) and integrase genes were sequenced in plasma samples from 782 consecutive patients on failing antiretroviral regimens, seen in 37 specialized centres in 2014. The genotyping results were interpreted using the ANRS v24 algorithm. Prevalence rates were compared with those obtained during a similar survey conducted in 2009. The protease and RT sequences were obtained in 566 patients, and the integrase sequence in 382 patients. Sequencing was successful in 60%, 78%, 78% and 87% of patients with VLs of 51-200, 201-500, 501-1000 and >1000 copies/mL, respectively. Resistance to at least one antiretroviral drug was detected in 56.3% of samples. Respectively, 3.9%, 8.7%, 1.5% and 3.4% of patients harboured viruses that were resistant to any NRTI, NNRTI, PI and integrase inhibitor (INI). Resistance rates were lower in 2014 than in 2009. Resistance was detected in 48.5% of samples from patients with a VL between 51 and 200 copies/mL. In France in 2014, 90.0% of patients in AIDS care centres were receiving antiretroviral drugs and 12.0% of them had VLs >50copies/mL. Therefore, this study suggests that 6.7% of treated patients in France might transmit resistant strains. Resistance testing may be warranted in all treated patients with VL > 50 copies/mL.