Failure In HIV-infected Patients Research Articles

Human Immunodeficiency Virus-1 Drug Resistance Mutations in Iranian Treatment-experienced Individuals.

Human immunodeficiency virus-1 infection still remains a global health threat. While antiretroviral therapy is the primary treatment option, concerns about the emergence of drug-resistance mutations and treatment failure in HIV-infected patients persist. In this study, we investigated the development of drug resistance in HIV-1-infected individuals receiving antiretroviral therapy for 6-10 years. In this cross-sectional study, we evaluated 144 people living with HIV-1 who had received antiretroviral therapy for at least 6 years. Plasma specimens were collected, and the HIV-1 viral load and drug-resistance mutations were assessed using molecular techniques. The demographic and epidemiological characteristics of the participants were also analyzed: Twelve [8.3%) of the studied patients showed a viral load over 1000 copies per/mL, which indicates the suboptimal response to antiretroviral therapy. Significant correlations were found between viral load and CD4 count, as well as epidemiological factors, such as vertical transmission, history of imprisonment, and needle stick injuries. Drug resistance mutations were detected in 10 (83.3%) of patients who failed on antiretroviral therapy, with the most common mutations observed against nucleoside reverse transcriptase inhibitors (5 (41.7%)) and non-nucleoside reverse transcriptase inhibitors (9 (75%)). Phylogenetic analysis revealed that 12 patients who failed treatment were infected with CRF35_AD. Our study provides important insights into the characteristics and development of drug resistance in HIV-1-infected individuals receiving long-term antiretroviral therapy in Iran. The findings underline the need for regular viral load monitoring, individualized treatment selection, and targeted interventions to optimize treatment outcomes and prevent the further spread of drug-resistant strains.

Performances of Dried Blood Spots and Point-of-Care Devices to Identify Virological Failure in HIV-Infected Patients: A Systematic Review and Meta-Analysis

To broaden access to HIV viral load monitoring (VLM), the use of blood samples from dried blood spots (DBS) or point-of-care (POC) devices, could be of great help in settings where plasma is not easily accessible. The variety of assays available makes the choice complex. This systematic review and meta-analysis aims to estimate the sensitivity and specificity of DBS and POC devices to identify patients in virological failure using World Health Organization (WHO) recommendations (viral load ≥1000 copies/mL), compared with plasma, for the assays currently available. Four databases were searched for articles, and two reviewers independently identified articles reporting sensitivity and specificity of DBS and/or POC to identify patients in virological failure. We excluded articles that used other thresholds as well as articles with a total number of participants below 50 to avoid reporting bias. Heterogeneity and factors associated with assays' performances were assessed by I2 statistics and metaregression. The protocol of this review follows the PRISMA guidelines. Out of 941 articles, 47 were included: 32 DBS evaluations and 16 POC evaluations. Overall, when using DBS, the Abbott RT HIV-1, Roche CAP-CTM, NucliSENS BioMerieux and Aptima assays presented sensitivity and specificity exceeding 85%, but reported results were highly heterogeneous. Factors associated with better performances were high volume of blood and the use of the same assay for DBS and plasma VLM. Regarding the POC devices, SAMBA I, SAMBA II, and GeneXpert devices presented high sensitivity and specificity exceeding 90%, with less heterogeneity. DBS is suitable VLM, but performances can vary greatly depending on the protocols, and should be performed in trained centers. POC is suitable for VLM with less risk of heterogeneity but is more intensive in costs and logistics.

Higher Risk of Mortality and Virologic Failure in HIV-Infected Patients With High Viral Load at Antiretroviral Therapy Initiation: An Observational Cohort Study in Chongqing, China.

BackgroundViral load (VL) is a strong predictor of human immunodeficiency virus (HIV) disease progression. The aim of this study was to evaluate the effect of high baseline VL on antiretroviral therapy (ART) outcomes among HIV-infected patients.MethodsThis retrospective study observed HIV-infected patients who had baseline VL test at ART initiation between 2015 and 2019 in Chongqing, China. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on Acquired immunodeficiency syndrome (AIDS)-related mortality and virologic failure, respectively.ResultsThe cohort included 7,176 HIV-infected patients, of whom 38.7% had a baseline VL ≥ 100,000 copies/mL. Of the patients who died during follow-up, 58.9% had a baseline VL ≥ 100,000 copies/mL. Compared with a baseline VL < 10,000 copies/mL, ART initiation at VL ≥ 100,000 copies/mL was significantly associated with the AIDS-related death (adjusted hazard ratio, AHR = 1.4) and virologic failure (adjusted odds ratio, AOR = 2.4). Compared with patients with a baseline VL < 10,000 copies/mL, patients on the recommended first-line regimen with a VL ≥ 100,000 copies/mL at ART initiaition had higher mortality rate (5.1 vs. 1.7 per 100 person-years), but there was no significant difference in the mortality accoding to the initial VL level among patients on second-line ART (2.8 vs. 2.7 per 100 person-years). ART initiation ≤ 30 days after HIV diagnosis was associated with a lower risk of AIDS-related death (AHR = 0.6).ConclusionsART initiation with VL ≥ 100,000 copies/mL was associated with a significantly greater risk of mortality and virologic failure. Optimizing the ART regimen and initiating ART early may help to reduce mortality effectively among patients with a high baseline VL. VL testing for all HIV patients is recommended at HIV diagnosis or on ART initiation.

Consequences of HIV/Syphilis Co-Infection on HIV Viral Load and Immune Response to Antiretroviral Therapy.

IntroductionAlthough syphilis is a frequent co-infection in patients with human immunodeficiency virus (HIV) infection, the influence of syphilis on immune response and virologic failure in HIV-infected patients following initiation of antiretroviral therapy (ART) is not well-defined.MethodsA retrospective study was conducted at Tianjin Second People’s Hospital to evaluate the prevalence of syphilis and immune status in 4171 ART-naïve patients. The study included patients who initiated ART between August 2009 and June 2019.ResultsThe prevalence of syphilis was 40.1% in all ART-naïve patients and 42.5% in ART-naïve men who have sex with men. HIV/syphilis co-infection was associated with higher virologic failure (odds ratio (95% confidence interval): 1.30 (1.04, 1.63)). Patients with HIV/syphilis co-infection had lower median CD4+ T cell counts and CD4/CD8 ratios at baseline. After initiation of ART, patients co-infected with HIV/syphilis had smaller increases in CD4+ T cell counts and CD4/CD8 ratios than patients infected only with HIV. The rate of recurrence of syphilis or reinfection was 9% (n = 128) during seven years of ART.ConclusionHIV/syphilis co-infection had a negative impact on immune recovery and antiretroviral effectiveness. RPR titer and HIV viral load should be monitored in patients co-infected with HIV/syphilis, especially in patients with high RPR titers.

High failure rates of protease inhibitor-based antiretroviral treatment in rural Tanzania - A prospective cohort study.

BackgroundPoor adherence to antiretroviral drugs and viral resistance are the main drivers of treatment failure in HIV-infected patients. In sub-Saharan Africa, avoidance of treatment failure on second-line protease inhibitor therapy is critical as treatment options are limited.MethodsIn the prospective observational study of the Kilombero & Ulanga Antiretroviral Cohort in rural Tanzania, we assessed virologic failure (viral load ≥1,000 copies/mL) and drug resistance mutations in bio-banked plasma samples 6–12 months after initiation of a protease inhibitor-based treatment regimen. Additionally, viral load was measured before start of protease inhibitor, a second time between 1–5 years after start, and at suspected treatment failure in patients with available bio-banked samples. We performed resistance testing if viral load was ≥1000 copies/ml. Risk factors for virologic failure were analyzed using logistic regression.ResultsIn total, 252 patients were included; of those 56% were female and 21% children. Virologic failure occurred 6–12 months after the start of a protease inhibitor in 26/199 (13.1%) of adults and 7/53 of children (13.2%). The prevalence of virologic failure did not change over time. Nucleoside reverse transcriptase inhibitors drug resistance mutation testing performed at 6–12 months showed a positive signal in only 9/16 adults. No cases of resistance mutations for protease inhibitors were seen at this time. In samples taken between 1–5 years protease inhibitor resistance was demonstrated in 2/7 adults. In adult samples before protease inhibitor start, resistance to nucleoside reverse transcriptase inhibitors was detected in 30/41, and to non-nucleoside reverse-transcriptase inhibitors in 35/41 patients. In 15/16 pediatric samples, resistance to both drug classes but not for protease inhibitors was present.ConclusionOur study confirms high early failure rates in adults and children treated with protease inhibitors, even in the absence of protease inhibitors resistance mutations, suggesting an urgent need for adherence support in this setting.

Immunological recovery failure in cART-treated HIV-positive patients is associated with reduced thymic output and RTE CD4+ Tcell death by pyroptosis.

Despite more than three decades of studies and advances in combination antiretroviral therapy (cART) against human immunodeficiency virus (HIV), the mechanisms that precisely determine immune reconstitution failure have not been completely elucidated yet. Thus, this study aimed to investigate the thymic function, immune activation, and cell death by pyroptosis and apoptosis in virologically suppressed HIV-positive patients receiving cART. Immunophenotyping analyses were performed in 57 cART-treated HIV-infected patients with undetectable plasma viral load, who were classified as immunological nonresponders (INR=29) and immunologic responders (IR=28). Sociodemographic and clinical data were also assessed from medical records. Twelve healthy volunteers were also included in this study. The INR showed lower pretreatment CD4+ Tcell count that remained low even after 1 yr of treatment, lower CD4/CD8 ratio, lower percentage of recent thymic emigrant (RTE) CD4+ Tcell (CD45RA+CD31+) and naïve CD4+ Tcell (CD45RA+CD62L+), higher levels of effector memory CD4+ Tcells (CD45RA-CD62L-), and higher pyroptosis levels of RTE CD4+ Tcells (CD31+FLICA-Caspase1+) when compared with IR. Our findings indicate that reduced thymic function and RTE CD4+ Tcell death by pyroptosis are the major mechanisms of immunological recovery failure in HIV-infected patients receiving cART.

Coinfection between human immunodeficiency virus and tuberculosis: A consideration on ritonavir-related heme Oxygenase-1 pathway

Background: Human immunodeficiency virus (HIV) infection is an important infection seen worldwide. HIV-infected patients usually have impaired immune function and get infected with other concurrent infections. Tuberculosis is a common concurrent infection in HIV-infected cases. The effect of coinfection and the response to the standard antiretroviral therapy in HIV-infected patients with concurrent tuberculosis infection is interesting. Methods: The aim of this study is to assess the effect of pharmacological pathway of ritonavir on tuberculosis treatment in HIV-infected patients with concurrent tuberculosis infection. The standard network pharmacology analysis is performed. Results: According to the network pharmacology analysis, the identified linkage is heme oxygenase-1. The ritonavir can result in increased expression of heme oxygenase-1 that further possible induces tuberculosis treatment failure in HIV-infected patients with concurrent tuberculosis infection. Conclusion: Ritonavir-related heme oxygenase-1 pathway is an important pathway that might affect the treatment of tuberculosis. Ritonavir dosage adjustment for tuberculosis treatment in HIV-infected patients with concurrent tuberculosis infection is necessary.

Prevalence and risk factors of mild chronic renal failure in HIV-infected patients: influence of female gender and antiretroviral therapy

BackgroundIn people living with HIV, much is known about chronic kidney disease, defined as a glomerular filtration rate under 60mL/min. However, there is scarce data about prevalence and risk factors for milder impairment (60–89mL/min). ObjectiveThe present study aims to assess the influence of sex, antiretroviral therapy, and classical risk factors on the occurrence of mild decreased renal function in a large Spanish cohort of HIV-infected patients. MethodsCross-sectional, single center study, including all adult HIV-1-infected patients under antiretroviral treatment with at least two serum creatinine measures during 2014, describing the occurrence of and the risk factors for mildly decreased renal function (eGFR by CKD-EPI creatinine equation of 60–89mL/min). ResultsAmong the 4337 patients included, the prevalence rate of mildly reduced renal function was 25%. Independent risk factors for this outcome were age older than 50 years (OR 3.03, 95% CI 2.58–3.55), female sex (OR 1.23, 95% CI 1.02–1.48), baseline hypertension (OR 1.57, 95% CI 1.25–1.97) or dyslipidemia (OR 1.48, 95% CI 1.17–1.87), virologic suppression (OR 1.88, 95% CI 1.39–2.53), and exposure to tenofovir disoproxil-fumarate (OR 1.67, 95% CI 1.33–2.08) or ritonavir-boosted protease-inhibitors (OR 1.19, 95% CI 1.03–1.39). ConclusionsFemales and patients over 50 seem to be more vulnerable to renal impairment. Potentially modifiable risk factors and exposure to tenofovir disoproxil-fumarate or ritonavir-boosted protease-inhibitors are present even in earlier stages of chronic kidney dysfunction. It remains to be determined whether early interventions including antiretroviral therapy changes (tenofovir alafenamide, cobicistat) or improving comorbidities management will improve the course of chronic kidney disease.

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.

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.

Association of Tenofovir Use With Risk of Incident Heart Failure in HIV-Infected Patients.

BackgroundThe antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus–infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.Methods and ResultsWe identified 21 435 human immunodeficiency virus–infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus–related, and cardiovascular risk factors. During follow‐up, 438 incident HF events occurred. Unadjusted 5‐year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7‐1.1), 1.7 (1.4‐2.2), and 4.5 (3.9‐5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53‐0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68‐0.92). When limited to antiretroviral‐naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36‐0.78) compared to never users.ConclusionsAmong a large national cohort of human immunodeficiency virus–infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate.

Impact of peer support on virologic failure in HIV-infected patients on antiretroviral therapy - a cluster randomized controlled trial in Vietnam.

BackgroundThe effect of peer support on virologic and immunologic treatment outcomes among HIVinfected patients receiving antiretroviral therapy (ART) was assessed in a cluster randomized controlled trial in Vietnam.MethodsSeventy-one clusters (communes) were randomized in intervention or control, and a total of 640 patients initiating ART were enrolled. The intervention group received peer support with weekly home-visits. Both groups received first-line ART regimens according to the National Treatment Guidelines. Viral load (VL) (ExaVir™ Load) and CD4 counts were analyzed every 6 months. The primary endpoint was virologic failure (VL >1000 copies/ml). Patients were followed up for 24 months. Intention-to-treat analysis was used. Cluster longitudinal and survival analyses were used to study time to virologic failure and CD4 trends.ResultsOf 640 patients, 71% were males, mean age 32 years, 83% started with stavudine/lamivudine/nevirapine regimen. After a mean of 20.8 months, 78% completed the study, and the median CD4 increase was 286 cells/μl. Cumulative virologic failure risk was 7.2%. There was no significant difference between intervention and control groups in risk for and time to virologic failure and in CD4 trends. Risk factors for virologic failure were ART-non-naïve status [aHR 6.9;(95% CI 3.2–14.6); p < 0.01]; baseline VL ≥100,000 copies/ml [aHR 2.3;(95% CI 1.2–4.3); p < 0.05] and incomplete adherence (self-reported missing more than one dose during 24 months) [aHR 3.1;(95% CI 1.1–8.9); p < 0.05]. Risk factors associated with slower increase of CD4 counts were: baseline VL ≥100,000 copies/ml [adj.sq.Coeff (95% CI): −0.9 (−1.5;−0.3); p < 0.01] and baseline CD4 count <100 cells/μl [adj.sq.Coeff (95% CI): −5.7 (−6.3;−5.4); p < 0.01]. Having an HIV-infected family member was also significantly associated with gain in CD4 counts [adj.sq.Coeff (95% CI): 1.3 (0.8;1.9); p < 0.01].ConclusionThere was a low virologic failure risk during the first 2 years of ART follow-up in a rural low-income setting in Vietnam. Peer support did not show any impact on virologic and immunologic outcomes after 2 years of follow up.Trial registration NCT01433601.

Identifying Causes of Antiretroviral Treatment Failure in HIV-Infected Patients

Identifying Causes of Antiretroviral Treatment Failure in HIV-Infected Patients

Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14–1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.

High efficacy of first-line ART in a West African cohort, assessed by dried blood spot virological and pharmacological measurements.

The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples. Resistance genotype was assessed for all detectable VLs (limit of detection >100 copies/mL); antiretroviral concentrations were interpreted using standard plasma cut-offs after extrapolation of blood to plasma results. Median (IQR) results are presented. Two hundred and eighteen patients (61% women), aged 41 (34-46) years, with 138 (56-235) CD4 cells/mm3 at baseline were included. After 4 (2-6) years of follow-up under therapy, CD4 gain was +197 (98-372) cells/mm3; 81% had VL <800 copies/mL. Antiretroviral concentrations were adequate in 87% of patients and nevirapine/efavirenz concentrations were related to viral success (P < 0.001). DBS genotypic resistance amplification succeeded in 71% of failing patients: NRTI drug resistance mutations were identified in 73% including resistance to lamivudine/emtricitabine (67%), abacavir (30%) and tenofovir (21%); and NNRTI drug resistance mutations were identified in 82% including resistance to rilpivirine (39%) and etravirine (15%). This study demonstrated a good response after 4 years of first-line ART in Niger. Adherence was high, according to antiretroviral concentrations, and the majority of failures were explained by selection of drug resistance mutations detected in the DBS genotype. Using DBS might improve the assessment of ART failure in HIV-infected patients in low-income countries.

Epidemic Trend of HIV-1 Drug-Resistant Mutations Isolated From HIV-Infected Patients in Hebei, China from 2008 to 2013

Background: Widespread use of anti-HIV therapies has led to the global development of drug-resistant HIV strains. In China, our current knowledge of HIV- 1 strain variation, emerging epidemiological trends and viral genetics underlying drug resistance is limited. Method: Between 2008 and 2013, HIV-1 strains from 569 HIV-seropositive and AIDS patients undergoing antiviral treatment in Hebei province (China) were genotyped. ART-virological failure (viral load ≥ 1000 copies/ml) and HIV-1 mutations for these strains were analyzed, as were variations in mutation trends during this period. Results: ART-virological failure in HIV-infected patients decreased significantly between 2008 and 2013 (60.9% vs. 35.0%, p<0.05), and showed a significant decreasing trend (p<0.05). When all HIV-seropositive patients undergoing antiviral treatment were included in this analysis, however, differences or trends observed were not significant. Six mutations were detected in the HIV-1 protease coding region. Only one (A71V/T) showed a significant difference in prevalence during this period (p<0.05). Sixty-one mutations were found in the HIV-1 reverse transcriptase coding region, including 34 related to nucleoside reverse transcriptase inhibitor treatment and 27 related to non-nucleoside reverse transcriptase inhibitor treatment. Thirteen mutations (V75I, T215Y, M41L, L210W, T69D, D67DG, V118I, V75I/T, F77L, T215F, Q151M; NNRTI-related: V108I, M230L) exhibited significant decreasing trends between 2010 and 2013, and two mutations (K238T, V90I) showed significant increasing trends (p<0.05). Conclusion: Continuous monitoring of drug resistance is essential for the design of optimal regimens and improvement of therapeutic outcomes.

Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in HIV-Infected Patients in Mozambique.

In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available because of high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods with standard viral load testing. Blood was collected prospectively from 461 patients receiving first-line ART in Mozambique who had not been evaluated previously with viral load testing. Screening for virologic failure of ART was performed quantitatively (ie, standard viral loads) and qualitatively [one and 2 rounds of polymerase chain reaction (PCR)]. Individual samples and minipools of 5 samples were then analyzed using both methods. The relative efficiency, accuracy, and costs of each method were calculated based on viral load thresholds for ART failure. Standard viral load testing of individual samples revealed a high rate of ART failure (19%-23%) across all virologic failure thresholds, and the majority of the patients (93%) with viral loads >1500 copies per milliliter had genotypic resistance to drugs in their ART regimen. Pooled quantitative screening and deconvolution testing had positive and negative predictive values exceeding 95% with cost savings of $11,250 compared with quantitative testing of each sample individually. Pooled qualitative screening and deconvolution testing had a higher cost savings of $30,147 for 1 PCR round and $25,535 for 2 PCR rounds compared with quantitative testing each sample individually. Both pooled qualitative PCR methods had positive and negative predictive values ≥90%, but the pooled 1-round PCR method had a sensitivity of 64%. Given the high rate of undiagnosed ART failure and drug resistance in this cohort, it is clear that virologic monitoring is urgently needed in this population. Here, we compared alternative methods of virologic monitoring with standard viral load testing of individual samples and found these methods to be cost saving and accurate. The test characteristics of each method will likely need to be considered for each local population before it is adopted.

Low level viraemia and the risk of virological failure in HIV infected patients

Objective: to estimate the rate and the significance of low level viraemia in HIV positive patients registered in the National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, Romania. We retrospectively analysed the rate of HIV viral loads (VL) 200 and >1000 copies/mL) over a 12 months period. A low level VL was detected in 16.2% of the 3,916 evaluated patients, the rate of HIV RNA of 51-200 copies/mL being two times higher than the rate of a VL <50 copies/mL. A number of 84 patients had a VL<200 copies/mL after being HIV RNA undetectable. In these patients the risk of virological failure over a 12 months period was not correlated with the HIV VL group or the used antiretroviral treatment (protease inhibitors PI vs. non-PI containing regimen). A low level viraemia is a rather common event in the studied HIV patients. In previously undetectable patients a HIV RNA <200 copies/mL is not associated with an increased risk of virological failure in the next year.

Rate of and Predicting Factors for Virologic Failure in HIV-Infected Patients with Persistent Low-Level Viremia under Antiretroviral Therapy

To determine the rate of and predicting factors for virologic failure among HIV-infected patients with persistent low-level viremia (PLV) under antiretroviral therapy (ART), a retrospective cohort study was conducted among HIV-infected patients who experienced PLV under ART. Persistent low-level viremia was defined as HIV RNA level at 50 to 1000 copies/mL for at least 2 consecutive visits. Of 68 patients, mean ± standard deviation age was 35.2 ± 9.0 years and 64.7% were males. Median (interquartile range [IQR]) CD4 count was 94 (26-264) cells/mm(3) and baseline HIV RNA was 112 000 (1 090-461 500) copies/mL. During the median (IQR) follow-up period of 5.7 (3.4-10.3) years of ART, the rate of virologic failure was 38.2%. In multivariate analyses, only maximum amplitude of HIV RNA >400 copies/mL during PLV (hazard ratio = 5.668; 95% confidence interval, 1.888-17.014; P = .002) significantly predicted virologic failure. Patients with PLV >400 copies/mL are more likely to develop virologic failure and should be closely monitored. Interventional studies to prevent virologic failure in these patients are needed.

Predicting treatment failure in adults and children on antiretroviral therapy: a systematic review of the performance characteristics of the 2010 WHO immunologic and clinical criteria for virologic failure.

We systematically reviewed the performance of 2010 WHO immunologic and clinical criteria for predicting virologic failure in HIV-infected patients on antiretroviral therapy (ART). Systematic review. We used Cochrane Collaboration methods. We calculated unweighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of immunologic and clinical criteria for predicting virologic failure. We identified 18 studies. Sixteen assessed immunologic criteria in adults; 12 defined virologic failure as a plasma viral load of more than 50 to more than 1000 copies/ml in adults, three as viral load at least 5000 copies/ml, and two as viral load more than 10,000 copies/ml; the sensitivity ranged from 16.8 to 54.9%, specificity from 82.9 to 95.5%, PPV from 15.0 to 38.8%, and NPV from 90.9 to 98.6%. Seven studies assessed clinical criteria to predict viral load of more than 50 to more than 1000 copies/ml; the sensitivity was 11.0%, specificity 90.5%, PPV 44.9%, and NPV 90.2%. Seven studies assessed clinical or immunologic criteria defining virologic failure as viral load of more than 50 to more than 1000 copies/ml; their sensitivity was 26.6%, specificity 85.9%, PPV 49.4%, and NPV 91.1%. Four studies assessed immunologic criteria in children; three defined virologic failure as viral load at least 5000 copies/ml and one as viral load at least 400 copies/ml. The sensitivity ranged from 4.5 to 6.3%, specificity from 97.7 to 99.3%, PPV from 20.0 to 54.9%, and NPV from 85.5 to 91.8%. The 2010 WHO clinical and immunologic criteria are insensitive and have low PPV for predicting virologic failure. These data support the strong recommendation 2013 treatment guidelines that viral load testing be used to monitor for, diagnose, and confirm ART failure.