Antiretroviral Treatment Failure Research Articles

Characteristics and early outcomes of children and adolescents treated with darunavir/ritonavir-, raltegravir- or etravirine-containing antiretroviral therapy in the Western Cape Province of South Africa

Background. There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. Objective. To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens. Methods. This was a retrospective review of treatment-experienced children receiving a DRV/r-, RAL- or ETR-containing regimen as recommended by a paediatric expert review committee, based on HIV drug resistance testing. Results. Thirty-five children of median age 8.8 years (interquartile range (IQR) 5.5 - 11) who had received ART for a median of 6.9 years (IQR 5 - 9.9) and started a DRV/r-, RAL- or ETR-containing regimen were included. Before starting such a regimen, the median CD4+ lymphocyte count and HIV-1 RNA level were 405.5 cells/μL (IQR 251.5 - 541) and 28 314 copies/mL (IQR 5 595.5 – 120 186.5) (log 4.5 (IQR 3.7 - 5)), respectively, in 24 subjects with available results. After a median of 2 years (IQR 1.3 - 4) on treatment, 29/30 (96.7%) and 23/30 (76.7%) subjects with available results had HIV-1 RNA levels of <400 and <50 copies/mL, respectively. Conclusions. This study found DRV/r-, RAL- and ETR-containing regimens to be effective in a group of treatment-experienced children and adolescents with multidrug-resistant HIV. Although the treatment regimens in this study were individualised based on HIV genotyping results, further research evaluating the safety and efficacy of standardised third-line treatment regimens in children of all ages is needed.

Estimation of Clinical, Immunological and Virological Failure of First Line Antiretroviral Treatment in Kinshasa, Democratic Republic of Congo

Background: The prevalence of Human Immunodeficiency Virus (HIV) infection was 1.2% in the Democratic Republic of Congo, according to the Demographic Health Study report in 2014. In 2012, the severe failure rate to first-line ART in Kinshasa was estimated at more than 16%. Objective: The objective of this study is to determine the rate of clinical, immunological and virological failure in first-line treatment in Kinshasa. Methodology: At the 6th month of Antiretroviral Treatment (ART), 138 patients from a follow-up cohort of 8 centers in Kinshasa were received for paraclinical evaluations and analyses. The clinical and paraclinical parameters were recorded on the individual patient sheets as well as the survey forms. Clinical parameters, viral load and CD4 were evaluated at the 6th month of ART. Results: One hundred and thirty-eight (138) patients had returned for follow-up treatment, 81 women and 57 men. The average age of patients is 37 ± 12 years. The dominant age groups are those of 26 to 35 years and 36 to 45 years with 39 patients (28.3%) each, followed by those of 18 to 25 years (21.7%). One hundred and twenty-five (125) patients (90.5%) were in clinical stage 3 and 13 (9.5%) in clinical stage 4 according to the WHO classification. CD4 levels ranged from 98 to 1050 cells/mm3 and a median value of 560 cells/mm3. The median value of the patients’ VLs was 0.90 log10copies of RNA/ml with respective minimum and maximum values of 0 and 4.82 log10 copies of RNA/ml. The virological failure rate was 24.6%. Conclusions: The rate of virological failure of first-line antiretroviral treatment of patients under treatment in Kinshasa is 24.6% for the year 2015.

Poor Adherence Predictors and Factors Associated with Antiretroviral Treatment Failure among HIV Seropositive Patients in Western Nigeria

Poor Adherence Predictors and Factors Associated with Antiretroviral Treatment Failure among HIV Seropositive Patients in Western Nigeria

Predictors of first-line antiretroviral therapy failure amongst HIV-infected adult clients at Woldia Hospital, Northeast Ethiopia.

BackgroundDue to the limited availability of viral load testing for treatment outcome monitoring in resource limited settings, identifying predictive factors of antiretroviral treatment failure will help in selecting clients who will benefit most from the targeted use of viral load monitoring. Little is known about the predictors of treatment failure in the study area. This study was conducted to determine factors that predict first-line antiretroviral therapy failure among HIV-infected adult clients at Woldia Hospital, Northeast Ethiopia. For this study, antiretroviral therapy treatment failure was defined as the fulfillment of clinical and/or immunological criteria set by WHO.MethodsCase-control study was carried out from November to December 2014. Cases were adult clients who were on failing first line regimen and on active follow up while controls were those adult clients on a non-failing first-line regimen for 36 months and above and on active follow up. Data was entered in to Epi Info version 7 and was exported to SPSS version 20 for analysis. Binary logistic regression model was used to identify predictors of ART failure.ResultsA total of 59 cases and 245 controls were included in the analysis. Sixty three percent of the participants were females and the median age at ART enrollment was 33 years (IQR; 28, 40). The median baseline CD4count was not significantly different among cases and controls (105 (IQR = 60–174)vs.131 (IQR = 72.5–189.0); p = 0.301). The median peak CD4 count in the failure group (230 (IQR = 123–387)) was significantly low compared to the non-failure group (463 (IQR = 348.5–577)) [p < 0.001]. High peak CD4count (AOR = 0.993; 95% CI 0.990, 0.996) and longer duration on ART (AOR = 0.923; 95% CI 0.893, 0.954) were protective of treatment failure. In addition stavudine based regimen (AOR = 3.47; 95% CI 1.343, 10.555), low baseline BMI (AOR = 2.75; 95% CI 1.012, 7.457), unemployment (AOR = 4.93; 95% CI 1.493, 16.305) and formal educational level (AOR = 5.15; 95% CI 1.534, 17.276) were independently significant predictors of treatment failure.ConclusionsIn this setting low peak CD4count, shorter duration on first line ART, d4T based regimen, low baseline BMI, unemployment and formal educational level were significantly associated with increased treatment failure. Retaining patients on their initial first line regimen with appropriate follow up and improving their socioeconomic status through various livelihood initiatives should be strengthened.

Electronic health, telemedicine, and new paradigms for training and care.

HIV prevention and care is changing rapidly; guideline revisions and programmatic scale-up require innovative approaches to in-service training and care extension to improve provider practice and care access. We assessed recent (≤12 months) peer-reviewed publications on electronic health (eHealth), telemedicine, and other innovative provider-targeted interventions for HIV-related care. Key developments included systems merging electronic medical records (EMR) with provider clinical decision aids to prompt action, demonstration eHealth, and telemedicine projects, reviews or descriptions of technology to improve connectivity in lower resource settings, and a few trials on provider-centered interventions. Most publications were program reports and few data were available regarding efficacy of eHealth interventions for providers on patient HIV-related outcomes, notably identification and management of antiretroviral treatment failure in Kenya. Better evidence is needed for strategies to train providers and care extenders with the goal to improve impact of HIV prevention and care interventions. Rapid technology introduction and expansion may change the paradigm for improving provider knowledge and practice. Although new, the developments are promising for HIV provider-targeted eHealth and innovations for traditional training. More rigorous testing with randomized trials is needed to demonstrate impact on services for people living with HIV.

Effect of therapy switch on time to second-line antiretroviral treatment failure in HIV-infected patients.

BackgroundSwitch from first line antiretroviral therapy (ART) to second-line ART is common in clinical practice. However, there is limited knowledge of to which extent different reason for therapy switch are associated with differences in long-term consequences and sustainability of the second line ART.Material and methodsData from 869 patients with 14601 clinical visits between 1999–2014 were derived from the national cohort database. Reason for therapy switch and viral load (VL) levels at first-line ART failure were compared with regard to outcome of second line ART. Using the Laplace regression model we analyzed the median, 10th, 20th, 30th and 40th percentile of time to viral failure (VF).ResultsMost patients (n = 495; 57.0%) switched from first-line to second-line ART without VF. Patients switching due to detectable VL with (n = 124; 14.2%) or without drug resistance mutations (DRM) (n = 250; 28.8%) experienced VF to their second line regimen sooner (median time, years: 3.43 (95% CI 2.90–3.96) and 3.20 (95% 2.65–3.75), respectively) compared with those who switched without VF (4.53 years). Furthermore level of VL at first-line ART failure had a significant impact on failure of second-line ART starting after 2.5 years of second-line ART.ConclusionsIn the context of life-long therapy, a median time on second line ART of 4.53 years for these patients is short. To prolong time on second-line ART, further studies are needed on the reasons for therapy changes. Additionally patients with a high VL at first-line VF should be more frequently monitored the period after the therapy switch.

Antiretroviral Treatment Failure and Its Types Among Patients on Follow up at Zewditu Memorial Hospital, ART Clinic, Ethiopia: A Retrospective Study

Free antiretroviral therapy (ART) began in Ethiopia in March 2005 at Zewditu Memorial Hospital (ZMH) with technical assistance from Johns Hopkins University. Currently ZMH is the largest HIV clinic in the country providing HIV/AIDS treatment and care to more than 14,000 patients; of these 10,000 patients have started ART treatment. Though a significant number of the patients are responding to treatment, few patients have experienced treatment failure on first-line regimen and subsequently switched to second-line regimen. The objective of this study was to investigate the prevalence and the types of antiretroviral treatment failure among patients receiving antiretroviral therapy at ZMH. Using data abstraction format, demographic data, the type of treatment failure and the WHO staging of the disease were recorded for patients who were under treatment in different years starting from 01 January 2006 to 31 December 2011. The data were entered and analyzed using SPSS. The results indicated that the proportion of treatment failure to first-line ART in 2006, 2007, 2008, 2009, 2010 and 2011 were 2.12%, 1.40%, 1.10%, 0.73% , 0.88% and 0.16%, respectively. The major cause of ART failure was immunological (66%) followed by virologic (28.6%) and clinical failure (5.5%). In conclusion ART failure at ZMH is more prevalent in children than adults and the main type of treatment failure was found to be immunological. Keywords : antiretroviral treatment failure, prevalence and type, antiretroviral therapy clinic, Zewditu Memorial Hospital, Ethiopia,

Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy.

IntroductionAntiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered. If failure on first-line ART occurs, a combination of two nucleoside reverse transcriptase inhibitors (NRTIs) and boosted lopinavir or atazanavir is recommended.Materials and methodsPlasma was obtained from subjects with first (n = 174) or second-line (n = 99) treatment failure, as defined by clinical or immunological criteria, as well as from a control group of ART naïve subjects (n = 17) in Dar es Salaam, Tanzania. Amplification of the pol region was performed locally and the amplified DNA fragment was sent to Sweden for sequencing (split genotyping procedure). The therapeutic options after failure were assessed by the genotypic sensitivity score and the EuResist predictive engine. Viral load was quantified in a subset of subjects with second-line failure (n = 52).ResultsThe HIV-1 pol region was successfully amplified from 55/174 (32%) and 28/99 (28%) subjects with first- or second-line failure, respectively, and 14/17 (82%) ART-naïve individuals. HIV-1 pol sequence was obtained in 82 of these 97 cases (84.5%). Undetectable or very low (<2.6 log10 copies/10−3 L) viral load explained 19 out of 25 (76%) amplification failures in subjects at second-line ART failure. At first and second line failure, extensive accumulation of NRTI (88% and 73%, respectively) and NNRTI (93% and 73%, respectively) DRMs but a limited number of PI DRMs (11% at second line failure) was observed. First line failure subjects displayed a high degree of cross-resistance to second-generation NNRTIs etravirine (ETR; 51% intermediate and 9% resistant) and rilpivirine (RPV; 12% intermediate and 58% resistant), and to abacavir (ABC; 49% resistant) which is reserved for second line therapy in Tanzania. The predicted probability of success with the best salvage regimen at second-line failure decreased from 93.9% to 78.7% when restricting access to the NRTIs, NNRTIs and PIs currently available in Tanzania compared to when including all approved drugs.DiscussionThe split genotyping procedure is potential tool to analyse drug resistance in Tanzania but the sensitivity should be evaluated further. The lack of viral load monitoring likely results in a high false positive rate of treatment failures, unnecessary therapy switches and massive accumulation of NRTI and NNRTI mutations. The introduction of regular virological monitoring should be prioritized and integrated with drug resistance studies in resource limited settings.

Association of HIV/AIDS Clinician Warm Line Utilization with Diagnosis and Management of Antiretroviral Treatment Failure in Mozambique: A Retrospective Analysis of Program Data

In accordance with global HIV/AIDS goals, Mozambique is attempting to improve management of antiretroviral treatment failure (TF). We sought to determine whether the utilization of a national HIV/AIDS clinician telephone consultation service increased recognition and reporting of TF. In a retrospective analysis of routinely collected program data from telephone consultation logs and Mozambique’s national registry of second-line antiretroviral requests, we used linear mixed methods to describe the association between TF-related telephone consultations and submission of second-line requests, which required documentation of the TF diagnosis. The unit of analysis was the health facility. Available data included 1417 consultations (390 [27.5%] TF related) and 2662 second-line requests from 1011 health units (2015-2016 data). In multivariable analyses, each TF-related consultation was associated with an increase of 0.61 (95% confidence interval 0.15 to 1.06) second-line requests. In this setting, TF-related telephone consultation was positively and significantly associated with diagnosis and reporting of antiretroviral TF.

Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350–550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

Acceptability of a mobile health intervention to enhance HIV care coordination for patients with substance use disorders

BackgroundPersons living with HIV and substance use disorders face barriers to sustained engagement in medical care, leading to suboptimal antiretroviral treatment outcomes. Innovative mobile technology tools such as customizable smartphone applications have the potential to enhance existing care coordination programs, but have not been rigorously studied.MethodsWe developed and implemented a two-component intervention consisting of peer health navigation supported by a smartphone application conducting ecologic momentary assessment (EMA) of barriers to care and medication adherence. Patients with a history of antiretroviral treatment failure and substance use were recruited to participate in the 9-month pilot intervention. Three peer health navigators were trained to provide social and logistical support while participants re-engaged in HIV care. We assessed the acceptability of the intervention components using qualitative analysis of in-depth interviews conducted with study participants and peer navigators.ResultsOf 19 patients enrolled in the study, 17 participated for at least 2 months and 15 completed the entire 9-month study protocol. The acceptability of the peer navigation intervention was rated favorably by all participants interviewed, who felt that peer support was instrumental in helping them re-engage in HIV care. Participants also responded favorably to the smartphone application, but described its usefulness mostly as providing reminders to take medications and attend appointments, rather than as a facilitator of patient navigation.ConclusionsPeer health navigation and smartphone-based EMA are acceptable approaches to facilitating engagement in HIV care for drug using populations. Future studies to evaluate the efficacy of this approach for improving long-term retention in care and antiretroviral treatment outcomes are warranted.ClinicalTrials.gov Identifier NCT01941108; registered on September 4, 2013

Prevalence and Predictors of Clinical and Immunological Failure among Adults HIV Patients on HAART in Southern Benin

Objective: The purpose of this study was to determine the prevalence of antiretroviral therapy failure and to identify factors associated with failure in HIV infected patients on antiretroviral therapy. Methods: A six years retrospective cohort study was conducted. All HIV- infected patients on antiretroviral therapy for at least 12 months and followed in the outpatient treatment center at the CNHU-HKM in Cotonou were systematically included. The evaluation of the failure was clinical and immunological using the WHO 2010 criteria adapted by the Beninese national HIV/AIDS program. Data was extracted from ESOPE database and analyzed by SPSS 10.0. Multivariable linear regression was performed to identify predictors of antiretroviral treatment failure and p < 0.05 was considered to declare a statistical significance. Results: A total of 268 HIV infected patients were enrolled in the study. The overall prevalence of antiretroviral treatment failure was 35.4% (n=95), including thirty-one cases of clinical failure (11.6%), ten cases of immunological failure (6.3%) and forty-seven cases of clinico-immunological failure (17.5%). The mean age was 37 ± 22 years and the sex ratio was 0.71. Non-adherence to treatment was found to be the main cause of HARRT failure in 71.6% of cases (n=68). High levels of education, polygamy, advanced clinical stage (WHO stage IV) and a history of documented adverse effects were predictors of antiretroviral therapy failure. Difficulties in accessing routine viral loads and second-line molecules did not allow for early diagnosis and good management of HAART failure in Benin. Conclusion: The prevalence of clinical and immunological failure is high in this cohort. It is necessary to facilitate access to routine viral load as the main means of HAART monitoring and to make second-line molecules available.

Magnitude and predictors of antiretroviral treatment failure among HIV-infected children in Fiche and Kuyu hospitals, Oromia region, Ethiopia: a retrospective cohort study.

The objective of the study was to assess the magnitude and predictors of first‐line antiretroviral treatment failure among HIV‐infected children. A retrospective cohort study was conducted between January 2006 and December 2015. All pediatric patients of <15 years old and who took at least 6 months of ART in Fiche and Kuyu hospitals of Oromia region, Ethiopia were included in the study. Collected data were entered and analyzed using SPSS version 20. Multivariable logistic regression was employed to identify predictors of treatment failure. Data of 269 children were analyzed and majority (53.9%) of the children were males with a mean age of 9.8 ± 3.64 years. Based on the two WHO criteria, overall ART failure was found to be 51 (18.8%), of which 33 (12.26%) had clinical and 18 (6.69%) had immunologic failures. The mean time to the detection of treatment failure was 41 ± 24.96 months. Children's age between 6 and 9 years (AOR = 0.26, 95% CI: 0.09, 0.72) was protective toward treatment failure, while lost to follow‐up (AOR = 7.54, 95% CI: 2.35, 24.16), died (AOR = 22.22, 95% CI: 3.75, 131.54), transferred out (AOR = 3.34, 95% CI: 1.41, 7.87), suboptimal adherence to ART (AOR = 4.85, 95% CI: 1.82, 12.93), baseline CD4 count of <50 cells/mm3 (AOR = 4.28, 95% CI: 3.49, 5.9), and WHO advanced clinical stage (AOR = 2.46, 95% CI: 1.14, 5.31) were found to be predictors of treatment failure. The study revealed that the treatment failure is high and the mean time to develop treatment failure is short. The predictors for treatment failure were suboptimal adherence, lost to follow‐up, transferred out, initial CD4 count <50 cells/mm3, initial WHO stages 3 and 4. On the other hand, being in the age of 6–9 years is protective from developing treatment failure as compared to the other age category.

Incidence and Predictors of Anti-Retroviral Treatment (ART) Failure among Adults Receiving HIV Care at Zewditu Memorial Hospital, Addis Ababa, Ethiopia

Background: Despite availability of antiretroviral therapy, HIV is responsible for 2.7 million new infections and 2.0 million deaths from worldwide. Anti-Retroviral treatment failure is not a commonly diagnosis in healthcare facilities in Ethiopia and there is dearth of information on the extent and predictors of treatment failure among adults receiving HIV care in the study setting. The aim of the current study is to assess the incidence and predictors of Anti-Retroviral Treatment (ART) failure among adults receiving HIV care at Zewditu Memorial Hospital, Addis Ababa, Ethiopia. Methods: Facility based retrospective cohort study design was employed on archived data from 2011 to 2016. Data compilation checklist was developed from intake card and ART follow-up card. The collected data were coded and entered using Epi Info 7 and analysed using Statistical Packages for Social Science (SPSS) version 20 software. Results: The overall incidence rate of ART treatment failure were 4.91 cases per person months follow up with 2.1, 0.24 and 0.13 immunological, clinical and virological treatment failure cases per 100 person years of follow-up respectively. Conclusion: The incidence of Anti-Retroviral Treatment failure was considerable among the study participants. The predictors for ART failure were WHO stage 3 at start, CD4 count at base line, disclosure and opportunistic infections. Comprehensive interventions have to be in place to tackle treatment failure among adults on ART through rendering optimum care focusing on adults with advanced WHO stage, lower CD4 count at baseline, opportunistic infections and people who did not disclose their HIV status.

English

As the use of highly active antiretroviral therapy (HAART) increases, the issue of drug resistance and subsequent anti-retroviral treatment (ART) failure appears as a challenge. The study aim to assess prevalence of ART treatment failure and associated factors amongst children on ART at Gondar University Hospital, North WEST Ethiopia, 2014. A retrospective cross-sectional study was conducted on children taking ART at Gondar University Hospital by using a systematic random sampling technique to include 225 under 15 Children on ART who took the drugs for at least six months. Data was collected from the patients’ medical records and analyzed by SPSS version 16.0. Binary logistic regression with multivariate analysis was used. Data from 225 children was analyzed, where the mean age was 10.8 years. The majority of children (77.4%) were in advanced clinical stage before initiation of HAART. About 60% of children were started with regimen of AZT-3TC-NVP. The original first line regimen was substituted in 44.9% of patients. About 101 patients who took ART for a mean of 60.3 months had poor adherence. There were 41 patients (18.2%) who had evidence of first line ART treatment failure of which the most common type is both clinical and immunological. Out of all children with first line ART treatment failure, only 14 patients (34%) were detected and started on second line regimens. ARV prophylaxis for PMTCT (p=0.041), advanced clinical stage 3(p=0.046) and stage 4(p=0.035), base line CD4 less than 200 cells or 10% (p<0.001), tuberculosis co-infection (p=0.045), substitution of original regimen (p=0.001), poor adherence during follow up (p= 0.002) and duration of ART above 60 months (p=0.033) were independent risk factors for ART treatment failure. Key words: HIV/AIDS, clinical and immunological treatment failure, risk factors, Ethiopia.

Identifying Causes of Antiretroviral Treatment Failure in HIV-Infected Patients

Identifying Causes of Antiretroviral Treatment Failure in HIV-Infected Patients

First-line antiretroviral treatment failure and associated factors in HIV patients at the University of Gondar Teaching Hospital, Gondar, Northwest Ethiopia.

BackgroundAntiretroviral therapy (ART) restores immune function and reduces HIV-related adverse outcomes. But treatment failure erodes this advantage and leads to an increased morbidity and compromised quality of life in HIV patients. The aim of this study was to determine the prevalence and factors associated with first-line ART failure in HIV patients at the University of Gondar Teaching Hospital.Patients and methodsA retrospective study was conducted on 340 adults who had started ART during the period of September 2011 to May 2015. Data regarding patients’ sociodemographics, baseline characteristics, and treatment-related information were collected through review of their medical charts. Data were analyzed using SPSS version 21. Descriptive statistics, cross-tabs, and binary and multiple logistic regressions were utilized. P<0.05 was used to declare association.ResultsAmong the 340 patients enrolled, 205 were females (60.3%). The mean age at ART initiation was 34.4 years. A total of 14 (4.1%) patients were found to have treatment failure. The median duration of treatment failure from initiation of treatment was 17.5 months (8–36 months). Poor adherence to treatment and low baseline CD4 cell count were found to be significant predictors of treatment failure.ConclusionThe prevalence of first-line ART failure was 4.1%. Treatment failure was most likely to occur for the patients who had poor drug adherence and those who were delayed to start ART till their CD4 cell count became very low (<100 cells/mm3).

Brief Report: HIV-1 Tropism During Primary Infections in France: 1996-2014.

HIV-1 was mainly CCR5 tropic in recent seroconverters. We analyzed the coreceptor use in 239 primary HIV-1 infections (PHIs) between 1996 and 2014 using a validated recombinant virus phenotypic entry assay. CXCR4-using viruses were detected in 8.3%, 3.8%, and 6.1% of PHIs from 1996 to 2004, 2005 to 2009, and 2010 to 2014, respectively. The presence of CXCR4-using viruses was associated with the virological failure of antiretroviral treatment initiated during PHI (odds ratio, 7.9; 95% confidence interval, 1.1 to 56.5). The phenotypic tropism assay data show that the prevalence of X4 tropic transmitted viruses was stable in this French cohort of PHIs between 1996 and 2014.

Misclassification of Antiretroviral Treatment Failure Using WHO 2006 and 2010/2013 Immunologic Criteria in HIV-Infected Children and Adolescents in Western Kenya.

We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds.

Exploiting HIV-1 protease and reverse transcriptase cross-resistance information for improved drug resistance prediction by means of multi-label classification

BackgroundAntiretroviral therapy is essential for human immunodeficiency virus (HIV) infected patients to inhibit viral replication and therewith to slow progression of disease and prolong a patient’s life. However, the high mutation rate of HIV can lead to a fast adaptation of the virus under drug pressure and thereby to the evolution of resistant variants. In turn, these variants will lead to the failure of antiretroviral treatment. Moreover, these mutations cannot only lead to resistance against single drugs, but also to cross-resistance, i.e., resistance against drugs that have not yet been applied.Methods662 protease sequences and 715 reverse transcriptase sequences with complete resistance profiles were analyzed using machine learning techniques, namely binary relevance classifiers, classifier chains, and ensembles of classifier chains.ResultsIn our study, we applied multi-label classification models incorporating cross-resistance information to predict drug resistance for two of the major drug classes used in antiretroviral therapy for HIV-1, namely protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). By means of multi-label learning, namely classifier chains (CCs) and ensembles of classifier chains (ECCs), we were able to improve overall prediction accuracy for all drugs compared to hitherto applied binary classification models.ConclusionsThe development of fast and precise models to predict drug resistance in HIV-1 is highly important to enable a highly effective personalized therapy. Cross-resistance information can be exploited to improve prediction accuracy of computational drug resistance models.Electronic supplementary materialThe online version of this article (doi:10.1186/s13040-016-0089-1) contains supplementary material, which is available to authorized users.