Genotypic Antiretroviral Resistance Testing Research Articles

Evolution of HIV-1 Surveillance Drug Resistance Mutations Over 10 Years in New South Wales, Australia.

New South Wales has the greatest burden of HIV in Australia, with 2012 and 2013 recording the highest rates of new diagnoses in 20 years. Concurrently, there has been significant changes in antiretroviral treatments and testing paradigms. We compiled a statewide resistance database to characterize changes in HIV-1 resistance mutations over time. Genotypic antiretroviral resistance testing (GART) was performed on request at three reference laboratories using commercial and in-house methods. In total, 7629 HIV-1 polymerase sequences obtained from GART from 2004 to 2013 were retrospectively collated, reformatted, de-identified, and analyzed using Stanford HIVdb program 7.0 and the 2009 World Health Organization (WHO) surveillance drug resistance mutations (SDRMs). Analyses were performed on subgroups of known treatment naives, treatment experienced, and seroconverters. There has been a decrease in overall rates of prevalent drug resistance mutations from 57.8% in 2004 to 21% in 2013. Dual and triple class resistance mutations have decreased from 32.7% in 2004 to 5.8% in 2013 and 16.4% to 1.2%, respectively. In treatment-naive individuals (n = 450), the frequency of protease inhibitor (PI) mutations remains low at 2.7%. In seroconverters, rates of transmitted drug resistance (TDR) are 6.6%, 3%, 3%, and 1.5% for overall, PI, non-nucleoside reverse transcription inhibitor (NNRTI), and NRTI, respectively. In treatment experienced, rates remain stable with 36.0%, 18.9%, 29.1%, and 6.4% for overall, NNRTI, NRTI, and PI mutations. The most common mutations in treatment experienced occurred at position M184, T215 (NRTI); K103 (NNRTI); I54 (PI). Apparent decreases in prevalent SDRMs can be attributed to changes in GART testing indications over time. In treatment-naive and -experienced subgroups, rates have been stable with low rates of TDR in seroconverters.

Comparative analyses of published cost effectiveness models highlight critical considerations which are useful to inform development of new models

Background: Comparative analyses of published cost effectiveness models provide useful insights into critical issues to inform the development of new cost effectiveness models in the same disease area.Objective: The purpose of this study was to describe a comparative analysis of cost-effectiveness models and highlight the importance of such work in informing development of new models. This research uses genotypic antiretroviral resistance testing after first line treatment failure for Human Immunodeficiency Virus (HIV) as an example.Method: A literature search was performed, and published cost effectiveness models were selected according to predetermined eligibility criteria. A comprehensive comparative analysis was undertaken for all aspects of the models.Results: Five published models were compared, and several critical issues were identified for consideration when developing a new model. These include the comparator, time horizon and scope of the model. In addition, the composite effect of drug resistance prevalence, antiretroviral therapy efficacy, test performance and the proportion of patients switching to second-line ART potentially have a measurable effect on model results. When considering CD4 count and viral load, dichotomizing patients according to higher cost and lower quality of life (AIDS) versus lower cost and higher quality of life (non-AIDS) status will potentially capture differences between resistance testing and other strategies, which could be confirmed by cross-validation/convergent validation. A quality adjusted life year is an essential outcome which should be explicitly explored in probabilistic sensitivity analysis, where possible.Conclusions: Using an example of GART for HIV, this study demonstrates comparative analysis of previously published cost effectiveness models yields critical information which can be used to inform the structure and specifications of new models.

Prospective Evaluation of the Vela Diagnostics Next-Generation Sequencing Platform for HIV-1 Genotypic Resistance Testing

Genotypic antiretroviral drug resistance testing is a critical component of the global efforts to control the HIV-1 epidemic. This study investigates the semiautomated, next-generation sequencing (NGS)-based Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay in a prospective cohort of HIV-1-infected patients. Two-hundred sixty-nine samples were successfully sequenced by both NGS and Sanger sequencing. Among the 261 protease/reverse transcriptase (PR/RT) sequences, a mean of 0.37 drug resistance mutations were identified by both Sanger and NGS, 0.08 by NGS alone, and 0.03 by Sanger alone. Among the 50 integrase sequences, a mean of 0.3 drug resistance mutations were detected by both Sanger and NGS, and 0.08 by NGS alone. NGS estimated higher levels of drug resistance to one or more antiretroviral drugs for 6.5% of PR/RT sequences and 4.0% of integrase sequences, whereas Sanger estimated higher levels of drug resistance for 3.8% of PR/RT sequences. Although the samples successfully sequenced by the Sentosa SQ HIV Genotyping Assay demonstrated similar predicted resistance compared with Sanger, 44% of Sentosa runs failed quality control requiring 17 additional runs. This semi-automated NGS-based assay may aid in HIV-1 genotypic drug resistance testing, though numerous quality control issues were observed when this platform was used in a clinical laboratory setting. With additional refinement, the Sentosa SQ HIV-1 Genotyping Assay may contribute to the global efforts to control HIV-1.

A Clinical Prediction Rule for Protease Inhibitor Resistance in Patients Failing Second-Line Antiretroviral Therapy.

Background:Most adults with virological failure on second-line antiretroviral therapy (ART) in resource-limited settings have no major protease inhibitor (PI) resistance mutations. Therefore, empiric switches to third-line ART would waste resources. Genotypic antiretroviral resistance testing (GART) is expensive and has limited availability. A clinical prediction rule (CPR) for PI resistance could rationalize access to GART.Setting:A private sector ART cohort, South Africa.Methods:We identified adults with virologic failure on ritonavirboosted lopinavir/atazanavir-based ART and GART. We constructed a multivariate logistic regression model including age, sex, PI duration, short-term adherence (using pharmacy claims), concomitant CYP3A4-inducing drugs, and viral load at time of GART. We selected variables for the CPR using a stepwise approach and internally validated the model by bootstrapping.Results:148/339 (44%) patients had PI resistance (defined as ≥ 1 major resistance mutation to current PI). The median age was 42 years (interquartile range 36–48), 212 (63%) were females, 308 (91%) were on lopinavir/ritonavir, and median PI duration was 2.6 years (interquartile range 1.6–4.7). Variables associated with PI resistance and included in the CPR were age {adjusted odds ratio (aOR) 1.96 (95% confidence interval [CI]: 1.42 to 2.70) for 10-year increase}, PI duration (aOR 1.14 [95% CI: 1.03 to 1.26] per year), and adherence (aOR 1.22 [95% CI: 1.12 to 1.33] per 10% increase). The CPR model had a c-statistic of 0.738 (95% CI: 0.686 to 0.791).Conclusions:Older patients with high adherence and prolonged PI exposure are most likely to benefit from GART to guide selection of a third-line ART regimen. Our CPR to select patients for GART requires external validation before implementation.

Reporting on the prevalence of antiretroviral drug resistance in a regional HIV population over 20 years: a word of caution.

Failure to achieve complete viral suppression with antiretroviral drugs (ARV) may lead to uncontrolled HIV replication, ARV resistance and negative outcomes. Monitoring and reporting of HIV resistance trends is important but problematic. We examined prevalent resistance rates in an HIV population over 20 years and document how rates may appear to vary greatly based solely on which parameters are utilized. We determined the annual use of genotypic antiretroviral resistance testing (GART) from 1995 to 2014 for all patients receiving HIV care in southern Alberta, Canada, and the presence of resistance mutations in those tested. The impact on prevalent resistance rates of using cumulative or latest GART was also determined. Between 1995 and 2014, the number of patients with GART increased from <1% to 71%. Prevalent resistance in patients with GART decreased from a high of 52% in 2003 to 25.8% in 2014. However, if prevalence rates were reported using all active patients as denominator, including those without GART, prevalence increased from 0.7% to 18.5%. Prevalence rates were 7% to 9% higher in any given year if cumulative GART rather than latest GART results were used. While prevalence resistance rates are decreasing, the precise rates being reported may vary due to increasing number of patients tested annually, using either the entire population as denominator or only patients with GART, and using either last or cumulative GART. Defining these parameters is critical if prevalence is to be compared over time or between HIV populations.

Maintaining the continuity of HIV-care records for patients transferring care between centers: challenges, workloads, needs and risks

ABSTRACTWith improved life expectancy, the medical records of HIV-infected patients are likely to be transferred repeatedly between HIV caregivers. The challenges, and risk for introducing medical error from incomplete record transfers are poorly understood. We measured number of requests for record transfer, the workload incurred, and explore, using genotypic antiretroviral resistance testing results (GART), the potential risk of incomplete records. Using retrospective database and chart review, we examined all patients followed at the Southern Alberta Clinic between 1 January 2004 and 1 January 2015, and determined how many patients transferred care into and out our program, the associated requests and the workload for record transfer. Using a complete record of all GART tests, the potential importance of absent historic records in current treatment decisions was analyzed. The annual churn rate was 22 ± 3.4%. We received requests for only 70% of patient records who had left our care. Median time for receipt of incoming medical records was 28 days; average clerical time for processing data was 2 hours/record. Of all GART results, 25% exhibited resistance. Of 111 patients with potentially misleading GART results (i.e., documented historical resistance not visible on more recent GART), 34 (30.6%) had moved in from elsewhere. Rigorous maintenance of the continuity of the HIV record is not universally practiced. Resources, costs and logistic challenges as well as a lack of appreciation of risks clearly shown by GART testing, may be relevant barriers. Addressing such issues is pressing as aging and transfers of care are increasingly common.

An observational study of antiretroviral drug resistance in treatment-naïve patients with HIV infection in New Zealand, from 2007 to 2011.

Background Genotypic testing for antiretroviral drug resistance is recommended for all patients newly diagnosed with HIV infection. This study sought to quantify the prevalence of antiretroviral drug resistance in treatment-naïve patients with HIV infection in New Zealand. All genotypic antiretroviral drug resistance testing in New Zealand is performed at LabPLUS, Auckland City Hospital. The clinicians who requested antiretroviral drug resistance testing during the period 2007-2011 were contacted and were asked to identify which patients with HIV infection were treatment-naïve at the time of testing. Results of the antiretroviral drug resistance tests for treatment-naïve patients with HIV infection were reviewed and the prevalence of resistance determined. Two hundred and 10 treatment-naïve patients with HIV infection who had antiretroviral drug resistance testing performed were included; 20 (10%) were found to have a significant resistance mutation. Nine patients had virus resistant to one or more nucleoside reverse transcriptase inhibitors, 13 to non-nucleoside reverse transcriptase inhibitors and one to protease inhibitors. The prevalence of antiretroviral drug resistance in treatment-naïve patients with HIV infection identified in this study is comparable to rates identified in studies from North America, the UK and Europe. This prevalence demonstrates the need for antiretroviral drug resistance testing for all treatment-naïve patients with HIV infection in New Zealand.

Emerging antiretroviral drug resistance in sub-Saharan Africa: novel affordable technologies are needed to provide resistance testing for individual and public health benefits.

In industrialized countries, viral load monitoring and genotypic antiretroviral drug resistance testing (GART) play an important role in the selection of initial and subsequent combination antiretroviral therapy (cART) regimens. In contrast, resource constraints in Africa limit access to assays that could detect virologic failure, transmitted drug resistance (TDR) and acquired drug resistance to cART. This has adverse consequences for both individual and public health. Although the further roll-out of antiretrovirals for prevention, including preexposure prophylaxis (PrEP) and universal test and treat (UTT) strategies, could reduce HIV-1 incidence, these strategies may increase TDR [1,2]. Here, we present arguments that the scale up of antiretrovirals use should be accompanied by cost-effective assays for early detection of virologic failure, surveillance of TDR and GART for individual patient management.

A qualitative PCR minipool strategy to screen for virologic failure and antiretroviral drug resistance in South African patients on first-line antiretroviral therapy

BackgroundThe high cost of commercial HIV-1 viral load tests for monitoring of patients on antiretroviral treatment limits their use in resource-constrained settings. Commercial genotypic antiretroviral resistance testing is even more costly, yet it provides important benefits. ObjectivesWe sought to determine the sensitivity and negative predictive value of a qualitative PCR targeting partial reverse transcriptase for detection of virologic failure when 5 patient specimens are pooled. Study designA total of 300 South African routine patient samples were included and tested in 60 pools of 5 samples each. A qualitative nested PCR was optimised for testing pools and individual samples from positive pools. All positive samples were sequenced to detect drug resistance-associated mutations. Results were compared to those of conventional viral load monitoring. ResultsTwenty-two of 60 pools tested positive. Individual testing yielded 29 positive individual samples. Twenty-six patients had viral loads of above 1000 copies/ml. The pooling algorithm detected 24 of those 26 patients, resulting in a negative predictive value of 99.3%, and a positive predictive value of 89.7%. The sensitivity for detecting patients failing therapy was 92%, with a specificity of 98.9%. Of the patients failing first-line ART, 83.3% had NRTI and 91.7% NNRTI resistance mutations. ConclusionsThe pooled testing algorithm presented here required 43% fewer assays than conventional viral load testing. In addition to offering a potential cost saving over individual viral load testing, it also provided drug resistance information which is not available routinely in resourced-limited settings.

The Cost of Antiretroviral Drug Resistance in HIV-Positive Patients

Antiretroviral (ARV) drug resistance limits treatment choices, often necessitating the selection of drugs with less desirable pill burdens, toxicity profiles, drug interactions and dosing schedules, and may increase cost. We examine the impact of resistance on the cost of HIV care. All adult HIV-positive individuals newly referred for HIV care from 1 January 2007 to 1 January 2011 and followed until 31 December 2011 at the Southern Alberta Clinic, Calgary, AB, Canada, were included. We determined the cost of all ARV drugs, and HIV-related outpatient and inpatient care, reported as mean per patient per month (PPPM) costs in 2011 Canadian dollars (CDN). Overall, 78% of patients received genotypic antiretroviral resistance testing (GART); 57% among ARV-naive patients, 21% after suspected viral failure, and 20% during a treatment interruption. Resistance was detected in 6%, 49% and 21% of all tests respectively. The total mean PPPM cost for patients with GART was CDN 1,179. Patients with primary resistance had mean total PPPM costs of CDN 956. Patients with no resistance had mean PPPM costs of CDN 1,058, by contrast with the CDN 1,291 costs of patients with secondary/acquired resistance. Mean costs for one, two or three ARV class resistance was CDN 1,278, 1,337 and 1,801, respectively. Mean PPPM costs increased by 31% from CDN 1,068 to 1,396, respectively, before and after a positive resistance test. Transmission of resistant virus as well as emergence of resistance during ARV therapy leads to increased costs. Mean costs increased by number of resistant classes. Routine GART and optimizing ARV regimens to avoid resistance might minimize the long-term costs of HIV care.

Deep Sequencing Reveals Minor Protease Resistance Mutations in Patients Failing a Protease Inhibitor Regimen

Standard genotypic antiretroviral resistance testing, performed by bulk sequencing, does not readily detect variants that comprise <20% of the circulating HIV-1 RNA population. Nevertheless, it is valuable in selecting an antiretroviral regimen after antiretroviral failure. In patients with poor adherence, resistant variants may not reach this threshold. Therefore, deep sequencing would be potentially valuable for detecting minority resistant variants. We compared bulk sequencing and deep sequencing to detect HIV-1 drug resistance at the time of a second-line protease inhibitor (PI)-based antiretroviral regimen failure. Eligibility criteria were virologic failure (HIV-1 RNA load of >500 copies/ml) of a first-line nonnucleoside reverse transcriptase inhibitor-based regimen, with at least the M184V mutation (lamivudine resistance), and second-line failure of a lopinavir/ritonavir (LPV/r)-based regimen. An amplicon-sequencing approach on the Roche 454 system was used. Six patients with viral loads of >90,000 copies/ml and one patient with a viral load of 520 copies/ml were included. Mutations not detectable by bulk sequencing during first- and second-line failure were detected by deep sequencing during second-line failure. Low-frequency variants (>0.5% of the sequence population) harboring major protease inhibitor resistance mutations were found in 5 of 7 patients despite poor adherence to the LPV/r-based regimen. In patients with intermittent adherence to a boosted PI regimen, deep sequencing may detect minority PI-resistant variants, which likely represent early events in resistance selection. In patients with poor or intermittent adherence, there may be low evolutionary impetus for such variants to reach fixation, explaining the low prevalence of PI resistance.

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.

Impact of Remote versus Local Sampling on Sensitivity of Genotypic Antiretroviral Resistance Testing

Genotypic tests are commonly used in clinical practice to infer human immunodeficiency virus type 1 (HIV-1) susceptibility to licensed antiretroviral drugs ([3][1]). Viral RNA extracted from patient plasma by standardized methods is used as the source material for reverse transcription (RT)-PCR

Genotypic Antiretroviral Resistance Testing for Human Immunodeficiency Virus Type 1 Integrase Inhibitors by Use of the TruGene Sequencing System

A sequencing assay for detection of mutations conferring resistance to human immunodeficiency virus type 1 (HIV-1) integrase inhibitors raltegravir and elvitegravir was developed using the automated TruGene sequencing system. The assay returned clear sequencing results for samples with >or=500 RNA copies/ml for mutation detection and HIV-1 subtyping across a spectrum of HIV-1 subtypes.

Genotypic antiretroviral drug resistance testing at low viral loads in the UK

Antiretroviral drug resistance testing is recommended in HIV-1 infected patients failing therapy in order to inform treatment selection. Although guidelines and test manufacturers recommend a viral load of at least 500-1000 HIV-1 RNA copies/mL for genotypic resistance testing to be performed, prompt management of virological failure could benefit from testing at lower viral load levels. Laboratories undertaking genotypic resistance testing were asked to provide figures for the number of resistance tests undertaken at viral loads <2000 copies/mL, the success rates of such tests and the extent of resistance detected, all stratified for viral load levels. Of the replies received, most laboratories were attempting resistance testing at viral loads below the recommended guidelines, with variable success and outcomes. This audit of current practice in the UK for undertaking genotypic resistance tests at viral loads <1000 copies/mL highlights the widespread use of such testing outside the British HIV Association guidelines.

Cost-Effectiveness of Genotypic Antiretroviral Resistance Testing in HIV-Infected Patients with Treatment Failure

BackgroundGenotypic antiretroviral resistance testing (GRT) in HIV infection with drug resistant virus is recommended to optimize antiretroviral therapy, in particular in patients with virological failure. We estimated the clinical effect, cost and cost-effectiveness of using GRT as compared to expert opinion in patients with antiretroviral treatment failure.MethodsWe developed a mathematical model of HIV disease to describe disease progression in HIV-infected patients with treatment failure and compared the incremental impact of GRT versus expert opinion to guide antiretroviral therapy. The analysis was conducted from the health care (discount rate 4%) and societal (discount rate 2%) perspective. Outcome measures included life-expectancy, quality-adjusted life-expectancy, health care costs, productivity costs and cost-effectiveness in US Dollars per quality-adjusted life-year (QALY) gained. Clinical and economic data were extracted from the large Swiss HIV Cohort Study and clinical trials.ResultsPatients whose treatment was optimized with GRT versus expert opinion had an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and two weeks, respectively. Health care costs with and without GRT were $US 421,000 and $US 419,000, leading to an incremental cost-effectiveness ratio of $US 35,000 per QALY gained. In the analysis from the societal perspective, GRT versus expert opinion led to an increase in discounted life-expectancy and quality-adjusted life-expectancy of three and four weeks, respectively. Health care costs with and without GRT were $US 551,000 and $US 549,000, respectively. When productivity changes were included in the analysis, GRT was cost-saving.ConclusionsGRT for treatment optimization in HIV-infected patients with treatment failure is a cost-effective use of scarce health care resources and beneficial to the society at large.

Performance of the TruGene Human Immunodeficiency Virus Type 1 Genotyping Kit and OpenGene DNA Sequencing System on Clinical Samples Diluted to Approximately 100 Copies per Milliliter

The TruGene human immunodeficiency virus type 1 (HIV-1) genotyping kit/OpenGene DNA sequencing system (Bayer HealthCare, Tarrytown, NY) reliably produced clinically acceptable resistance profiles for reverse transcriptase and protease inhibitors on patient samples diluted to approximately 100 copies/ml following extraction with the QIAamp viral RNA minikit (QIAGEN Inc., Valencia, CA). One modification of the standard protocol was made to guarantee PCR amplification: a centrifugation step to concentrate virus was added before RNA extraction. For genotypic antiretroviral resistance testing, no significant differences in the identification and sensitivity of detection for codon mutations, base mutations, and multibase sites were found between the original and diluted samples.

High-Risk Sexual Behavior in Adults With Genotypically Proven Antiretroviral-Resistant HIV Infection

The substantial frequency of drug resistance in persons recently infected with HIV implies exposure among HIV-uninfected individuals to HIV-infected persons with drug-resistant virus. Although there is an increasing emphasis on understanding high-risk behavior among HIV-infected patients, little work has focused on those with drug-resistant virus. We examined antiretroviral-treated patients with drug resistance in the Study of the Consequences of the Protease Inhibitor Era, a clinic-based cohort of HIV-infected adults. Sexual behavior was ascertained by self-administered questionnaire. Genotypic antiretroviral resistance testing was performed on isolates from participants with a plasma HIV RNA level > or =100 copies/mL. Among 279 participants on antiretroviral therapy, 168 (60%) had genotypic resistance to at least 1 drug. In those with drug resistance, 27% of men who have sex with men (MSM) and 11% of heterosexual men and women reported at least 1 episode of unprotected penile-anal or penile-vaginal intercourse in the previous 4 months; 17% of MSM and 6% of heterosexual participants reported unprotected intercourse with an HIV-uninfected or status unknown partner. In a multivariable model of predictors of unprotected anal or vaginal intercourse with an HIV-uninfected or status unknown partner, there was strong evidence for an effect of younger age, depression, and sildenafil use and moderate evidence for frequent alcohol use. Among HIV-infected patients with drug-resistant viremia, there is a substantial prevalence of high-risk sex with HIV-uninfected partners. The presence of definable risk factors for unsafe sex suggests a role for targeted rather than broad intervention, particularly when resources are limited.

Antiretroviral Drug Resistance Among Patients With Human Immunodeficiency Virus Who Act as Sources or Potential Sources in Occupational Accidents Involving Healthcare Workers

To determine human immunodeficiency virus (HIV) type 1 genotypic antiretroviral drug resistance profiles of patients presenting a risk or potential risk for occupational exposure of healthcare workers. Observational survey involving HIV-infected patients. Blood samples collected from source-patients and potential source-patients underwent HIV-1 genotypic antiretroviral resistance testing and determination of CD4 counts and viral load. Affected healthcare workers were monitored for 6 months after exposure. The survey was conducted in a tertiary-care hospital located in Sao Paulo, Brazil. Sao Paulo is considered the epicenter of the HIV-acquired immunodeficiency (AIDS) virus epidemic in Brazil. Source-patients, potential source-patients, and affected healthcare workers. A total of 371 occupational exposures to biological materials were reported, 46 (12.3%) of which were from HIV-seropositive source-patients. Samples from 18 source-patients and 26 patients considered "potential sources for accidents" were analyzed. Of these 44 samples, 18 (41%) presented resistance-related mutations in reverse transcriptase, protease, or both. Of these 18 samples, 16 (89%) had resistance to drugs included in the prophylactic schedule recommended by the Brazilian Ministry of Health. Use of the Centers for Disease Control and Prevention-Brazilian post-exposure prophylaxis regimen will result in the administration of antiretroviral agents to which the source HIV-1 isolate will often be resistant. Therefore, it would be advisable to carefully investigate the history of use of antiretroviral agents by source-patients and adjust the prophylactic therapy based on those data and, subsequently, the results of resistance testing.

A Longitudinal Analysis of Healthcare Costs after Treatment Optimization following Genotypic Antiretroviral Resistance Testing: Does Resistance Testing pay off?

To assess the impact of antiretroviral therapy optimized by genotypic antiretroviral resistance testing (GRT) on healthcare costs over a 2-year period in patients after antiretroviral treatment failure. Non-randomized, prospective, tertiary care, clinic-based study. One-hundred and forty-two HIV patients enrolled in the 'ZIEL' study and the Swiss HIV Cohort Study who experienced virological treatment failure. For all patients GRT was used to optimize the antiretroviral treatment regimen. All healthcare costs during 2 years following GRT were assessed using microcosting. Costs were separated into ART medication costs and healthcare costs other than ART medication (that is, non-ART medication costs, in-patient costs and ambulatory [out-patient] costs). These cost estimates were then split into four consecutive 6-month periods (period 1-4) and the accumulated cost for each period was calculated. Univariate and multivariate regression modelling techniques for repeated measurements were applied to assess the changes of healthcare costs over time and factors associated with healthcare costs following GRT. Overall healthcare costs after GRT decreased over time and were significantly higher in period 1 (32%; 95% confidence interval [Cl]: 18-47) compared with period 4. ART medication costs significantly increased by 1,017 (95% Cl: 22-2,014) Swiss francs (CHF) from period 1-4, whereas healthcare costs other than ART medication costs decreased substantially by a factor of 3.1 (95% Cl: 2.6-3.7) from period 1 to period 4. Factors mostly influencing healthcare costs following GRT were AIDS status, costs being 15% (95% Cl: 6-24) higher in patients with AIDS compared with patients without AIDS, and baseline viral load, costs being 12% (95% Cl: 6-17) higher in patients with each log increase in plasma RNA. Optimized antiretroviral treatment regimens following GRT lead to a reduction of healthcare costs in patients with treatment failure over 2 years. Patients in a worse health state (that is, a positive AIDS status and high baseline viral load) will experience higher overall costs.