Rate Of Virological Failure Research Articles

Long-term virological suppression on first-line efavirenz + tenofovir + emtricitabine/lamivudine for HIV-1.

Objectives:Evaluate long-term rates of virological failure and treatment interruption for people living with HIV (PLWHIV) with viral suppression on first-line efavirenz + tenofovir disoproxil fumarate + emtricitabine/lamivudine (EFV + TDF + FTC/3TC), and compare these according to patient characteristics.Methods:PLWHIV enrolled in the Collaboration of Observational HIV Epidemiological Research Europe cohort collaboration, who started first-line EFV + TDF + FTC/3TC at age at least 16 years and had viral suppression (<200 copies/ml) within 9 months were included. Rates of virological failure (≥200 copies/ml) and (complete) treatment interruption were estimated according to years since initial suppression. We used Poisson regression to examine associations of baseline characteristics with rates of virological failure or treatment interruption.Results:Among 19 527 eligible PLWHIV with median (interquartile range) follow-up 3.7 (2.0–5.6) years after initial viral suppression, the estimated rate of the combined incidence of virological failure or treatment interruption fell from 9.0/100 person-years in the first year to less than 4/100 person-years beyond 3 years from suppression; considering only those remaining on EFV + TDF + FTC/3TC, the combined rate dropped from 8.2/100 person-years in the first year to less than 3.5/100 person-years beyond 3 years. PLWHIV with injecting drug-related or heterosexual transmission were at higher risk of virological failure or treatment interruption, as were those of Black ethnicity. PLWHIV aged less than 35 years were at higher risk of virological failure and treatment interruption.Conclusion:PLWHIV starting first-line EFV + TDF + FTC/3TC had low rates of virological failure and treatment interruption up to 10 years from initial suppression. Demographic characteristics can be used to identify subpopulations with higher risks of these outcomes.

Antiretroviral Therapy-associated Adverse Drug Reactions and their Effects on Virologic Failure- A Retrospective Cohort Study in Nigeria.

Background: Adverse drug reactions (ADRs) associated with antiretroviral therapy (ART) can rapidly reverse the gains of ART resulting in poor health outcomes. We need an improved under-standing of specific ART-related ADRs that influence virologic outcomes.Objective: To investigate the frequency of clinical ADRs and assess their effect on virologic failure in patients on ART.Method: We described the prevalence of major clinical ADRs, and the association between specific ADRs and virologic failure in a clinic cohort of HIV-1 infected Nigerians aged ≥18 years, on first-line ART between June 2004 and February 2012. Multivariable logistic regression was run to identify predictors of virologic failure at 24 and 72 weeks of ART.Results: Data of 12,115 patients with a median age of 34 (interquartile range: 29-41) years, and pre-dominantly females (67%) were evaluated. Overall, 957 (7.9%) patients experienced at least one ADR during a median follow-up period of 4 years (interquartile range: 1-7). The three most prevalent ADRs were lipodystrophy (2.6%), anemia (1.9%), and skin rash (0.7%). Virologic failure rate was 36% and 34% at 24 and 72 weeks of ART, respectively. Anemia independently predicted the odds of virologic failure at 72 weeks of ART (adjusted odds ratio, 1.74; 95% CI: 1.2-2.51); adjusted for sex, age, pre-treatment CD4+ cell count, antiretroviral regimen, and medication refill adherence.Conclusion: Antiretroviral therapy-associated anemia increases the likelihood of late virologic failure. We recommend routine monitoring of hemoglobin levels and prompt management of anemia in all pa-tients on ART as a strategy to improve virologic success rates.

Glecaprevir/pibrentasvir in patients with chronic HCV and recent drug use: An integrated analysis of 7 phase III studies

Background: Injection drug use is the primary mode of transmission for hepatitis C virus (HCV), and treatment guidelines recommend treating HCV-infected people who use drugs; however, concerns about adherence, effectiveness, and reinfection have impeded treatment uptake.Methods: Data were pooled from seven phase III trials that evaluated the efficacy and safety of 8 or 12 weeks of glecaprevir/pibrentasvir (G/P) in patients chronically infected with HCV genotypes 1–6. Patients had compensated liver disease, with or without cirrhosis, and were HCV treatment-naïve or -experienced with interferon or pegylated interferon ± ribavirin, or sofosbuvir plus ribavirin ± pegylated interferon. Patients were grouped into recent drug users (injection drug use ≤12 months before screening, positive urine drug screen [UDS], and/or drug-related adverse event), former drug users (>12 months before screening and negative UDS), or non-drug users. Assessments included sustained virologic response at 12 weeks posttreatment (SVR12), treatment adherence, and safety.Results: Among 1819 patients, 5%, 34%, and 61% were recent, former, and non-drug users, respectively. Treatment adherence and completion were high (≥96%) regardless of drug use status. SVR12 was achieved by 93% (n/N = 91/98), 97% (n/N = 591/610), and >99% (n/N = 1106/1111) of recent, former, and non-drug users, respectively (intention-to-treat analysis). The overall rates of virologic failure were ≤1.5% across all three subpopulations, with no HCV reinfections among recent drug users. Drug-related serious adverse events and adverse events leading to treatment discontinuation were experienced by ≤1% of patients.Conclusions: G/P is a well-tolerated and efficacious pangenotypic regimen for chronic HCV-infected people with recent or active drug use.

Patterns of detectable viraemia among children and adults with HIV infection taking antiretroviral therapy in Zimbabwe

ObjectiveTo investigate the incidence and predictors of viraemia among individuals on antiretroviral therapy (ART) in Harare, Zimbabwe. MethodsChildren (0–19 years) and adults (>19 years) starting ART between 2013 and 2015 were followed for a median of 2.8 and 2.7 years, respectively. The incidence rates of virological failure (VF), low-level viraemia (LLV), and viral blips were assessed and the predictors of viraemia were determined using logistic and parametric survival regression analyses. ResultsA total of 630 individuals initiated ART, and 19.7% of children and 5.6% of adults did not achieve viral suppression by 12 months. Younger age and CD4 count ≤200 cells/mm3 at baseline were associated with not being virally suppressed at 12 months in adults. Among those who achieved viral suppression during the follow-up period, the incidence of VF was higher in children (4.0/100 person-years vs. 0.4/100 person-years in adults; p<0.001), as was the incidence of LLV (1.9/100 person-years vs. 0.3/100 person-years in adults; p=0.03). The incidence rate of blips was 10.9 per 100 person-years in children and 4.0 per 100 person-years in adults. ConclusionsChildren are less likely to reach viral suppression and are at higher risk of viraemia while on ART than adults. The significance of LLV and blips needs further study.

Compromise of Second-Line Antiretroviral Therapy Due to High Rates of Human Immunodeficiency Virus Drug Resistance in Mozambican Treatment-Experienced Children With Virologic Failure

Virologic failure (VF) is highly prevalent in sub-Saharan African children on antiretroviral therapy (ART) and is often associated with human immunodeficiency virus drug resistance (DR). Most children still lack access to routine viral load (VL) monitoring for early identification of treatment failure, with implications for the efficacy of second-line ART. Children aged 1 to 14 years on ART for ≥12 months at 6 public facilities in Maputo, Mozambique were consecutively enrolled after informed consent. Chart review and caregiver interviews were conducted. VL testing was performed, and specimens with ≥1000 copies/mL were genotyped. Of the 715 children included, the mean age was 103 months, 85.8% had no immunosuppression, 73.1% were taking stavudine/lamivudine/nevirapine, and 20.1% had a history prevention of mother-to-child transmission exposure. The mean time on ART was 60.0 months. VF was present in 259 patients (36.3%); 248 (95.8%) specimens were genotyped, and DR mutations were found in 238 (96.0%). Severe immunosuppression and nutritional decline were associated with DR. M184V and Y181C were the most common mutations. In the 238 patients with DR, standard second-line ART would have 0, 1, 2, and 3 effective antiretrovirals in 1 (0.4%), 74 (31.1%), 150 (63.0%), and 13 (5.5%) patients, respectively. This cohort had high rates of VF and DR with frequent compromise of second-line ART. There is urgent need to scale-up VL monitoring and heat-stable protease inhibitor formulations or integrase inhibitorsfor a more a durable first-line regimen that can feasibly be implemented in developing settings.

Brief Report: The Association of Chronic Pain and Long-Term Opioid Therapy With HIV Treatment Outcomes.

Chronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes. This was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site. Among 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03). Chronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.

High prevalence of virological failure and HIV drug mutations in a first-line cohort of Malawian children.

Drug resistance mutations (DRMs) increasingly jeopardize paediatric HIV programmes in sub-Saharan Africa. As individual monitoring of DRMs and viral loads has limited availability, population data on DRMs are essential to determine first-line susceptibility. Paediatric data from sub-Saharan Africa are scarce and unavailable for Malawi. To determine the prevalence of virological failure (VF) and DRMs among ART-naive HIV-infected Malawian children during the first year of first-line ART. In a prospective cohort of HIV-infected Malawian children, on first-line treatment, children were followed monthly; blood was collected for viral load testing (6 and 12 months) and genotypic resistance testing (12 months). VF was defined as at least one viral load >1000 copies/mL or death after 6 months of ART. DRMs were identified and susceptibility to NRTIs and NNRTIs was scored using the Stanford algorithm and by calculating genotypic susceptibility scores (GSSs). VF occurred in 66% (23/35) of the children during 12 months of follow-up. DRMs were detected in 44% (15/34); all had NNRTI resistance and 12% (4/34) had dual-class NNRTI/NRTI resistance. Reduced susceptibility (DRMs and GSS <3) was seen in 41% (14/34) to their current first-line regimen. High-level resistance was most common for nevirapine [26% (9/34)]. In this first report on VF and DRMs in children on first-line ART in Malawi, the rates of VF and DRMs were alarmingly high. Paediatric HIV programmes in sub-Saharan Africa should emphasize programmatic evaluation of VF and include detection of DRMs to adjust and design adequate first- and second-line regimens and prevent widespread resistance in children.

Comparison of effectiveness and discontinuation of interferon‐free therapy for hepatitis C in prison inmates and noninmates

Chronic hepatitis C treatment with direct acting antiviral (DAA) therapy during incarceration is an attractive option, due to its short duration and to the possibility of directly observed treatment or supervision. The aim of this study is to compare the effectiveness and rates of discontinuation of DAA treatment in prisoners and nonprisoners. We studied all patients treated in the 10 prisons of Catalonia and at 3 public hospitals in the Barcelona area between 1 January 2015 and 30 April 2016. We analysed sustained viral response (SVR) and rates of discontinuation through intention-to-treat and modified-intention-to-treat analyses, the latter excluding discontinuations due to release from prison. One hundred and eighty-eight inmates and 862 noninmates were included. Prisoners were significantly younger than nonprisoners, with higher proportions of men, drug users, HIV infection, genotypes 1a and 3 and more treatment with psychiatric drugs. Overall, 98.4% of patients completed treatment. The discontinuation rate was low, but higher in inmates (3.7% vs 1.2% noninmates; P=.003) and in community patients >65years old (2.8% vs 1.2% in under 65seconds; P=.008). Among the inmates, 7 (42.8%) discontinuations were due to release. SVR was 93.1% in inmates vs 96.5% in noninmates (P=.08) by intention-to-treat and 95.1% vs 96.5% (P=.37) by modified intention-to-treat. Virologic failure rates were similar (3.8% vs 3% in noninmates; P=.60). SVR, virologic failure and discontinuation rates were similar in inmates and noninmates. Currently, prisons are considered a priority for the implementation of DAA. Improved coordination between penitentiary and community health systems would help to ensure therapeutic continuity in released prisoners.

Patterns of emergent resistance-associated mutations after initiation of non-nucleoside reverse-transcriptase inhibitor-containing antiretroviral regimens in Taiwan: a multicenter cohort study.

BackgroundIncreasing trends of resistance-associated mutations (RAMs) to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) have raised concerns about the effectiveness of the regimens in the national HIV treatment programs in resource-limited countries. We aimed to retrospectively investigate the incidence and patterns of emergent RAMs of HIV-1 in HIV-positive adults experiencing virological failure to first-line nNRTI-containing combination antiretroviral therapy (cART) in Taiwan.Patients and methodsBetween June 2012 and March 2016, 1138 antiretroviral-naïve HIV-positive adults without baseline RAMs who initiated nNRTI-containing regimens were included for analysis. Virological failure was defined as plasma viral load (PVL) ≥200 copies/mL after 6 months of cART or confirmed PVL ≥200 copies/mL after achieving PVL <50 copies/mL. Population sequencing was retrospectively performed to detect baseline and emergent RAMs. RAMs were interpreted using the International AIDS Society-USA 2016 mutations list.ResultsSeventy-one patients (6.2%) developed virological failure, which occurred in 14.8% (43/291), 3.9% (26/675), and 1.2% (2/172) of patients receiving 2 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine, efavirenz, and rilpivirine, respectively. Among those, 53 (74.6%) had emergent RAMs identified, which included 43 (81.1%), 53 (100.0%), and 1 (1.9%) with RAMs to NRTIs, nNRTIs, and protease inhibitors, respectively; and 43 (81.1%) had multi-drug resistance. The most common emergent RAMs to NRTIs were M184V/I (42.3%) and K65R (28.2%), and those to nNRTIs were Y181C (42.3%), K103N (15.5%), G190A/E/Q (12.7%), V179D/E (12.7%), and V108I (9.9%).ConclusionWhile the rates of virological failure varied with the nNRTI used, the rate of emergent RAMs of HIV-1 to NRTIs and nNRTIs among the antiretroviral-naïve patients who failed nNRTI-containing cART remained low.

Nationwide Cohort Study of Antiretroviral Therapy Timing: Treatment Dropout and Virological Failure in China, 2011-2015.

People living with human immunodeficiency virus (PLWH) are still being diagnosed late, rendering the benefits of "early" antiretroviral therapy (ART) unattainable. Therefore, we aimed to evaluate the benefits of "immediate" ART. A nationwide cohort of PLWH in China who initiated ART January 1, 2011, to December 31, 2014 and had baseline CD4 results >200 cells/μL were censored at 12 months, dropout, or death, whichever came first. Treatment dropout and virological failure (viral load ≥400 copies/mL) were measured. Determinants were assessed by Cox and log-binomial regression. The cohort included 123605 PLWH. The ≤30 days group had a significantly lower treatment dropout rate of 6.72%, compared to 8.91% for the 91-365 days group and to 12.64% for the >365 days group. The ≤30 days group also had a significantly lower virological failure rate of 5.45% (31-90 days: 7.39%; 91-365 days: 9.64%; >365 days: 12.67%). Greater risk of dropout (91-365 days: adjusted hazard ratio [aHR] = 1.33, 95% confidence interval [CI] = 1.25-1.42; >365 days: aHR = 1.55, CI = 1.47-1.54), and virological failure (31-90 days: adjusted risk ratio [aRR] = 1.35, CI = 1.26-1.45; 91-365 days: aRR = 1.66, CI = 1.55-1.78; >365 days: aRR = 1.85, CI = 1.74-1.97) were observed for those who delayed treatment. ART within 30 days of HIV diagnosis was associated with significantly reduced risk of treatment failure, highlighting the need to implement test-and-immediately-treat policies.

Interferon-free treatment choice according to baseline RASs leads to high SVR rates in HCV genotype 1 infected patients.

Different combinations of direct antiviral agents (DAA) lead to high SVR rates in HCV genotype 1 infected patients. However, presence of baseline resistance-associated substitutions (RASs) represents a major risk factor for treatment failure. It is unknown whether choice of treatment based on RASs has the potential to decrease virologic failure rates. Population-based sequencing of NS3 and NS5A genes was performed in HCV genotype 1 infected patients at a German university hospital. Treatment was individually selected based on resistance analyses. In total, 319 patients (50% treatment-experienced and 30% with cirrhosis) were included. With the treatment choice based on the baseline NS3 and NS5A resistance profile SVR rates between 96 and 100% were observed in all subgroups, including treatment-experienced patients with cirrhosis and HCV genotype 1a infected cirrhotic patients. The choice of treatment based on the RASs status at baseline may be beneficial for optimizing treatment efficacy in patients with HCV genotype 1 infection and risk factors for treatment failure.

Virological failure on first-line antiretroviral therapy; associated factors and a pragmatic approach for switching to second line therapy-evidence from a prospective cohort study in rural South-Western Uganda, 2004-2011.

IntroductionWe investigated factors affecting Virological failure (VF) on first line Antiretroviral Therapy (ART) and evaluated a pragmatic approach to switching to second line ART.MethodsBetween 2004 and 2011, we assessed adults taking ART. After 6 months or more on ART, participants with VL >1000 copies/ml or two successive VL > 400 copies/ml (Conventional VF) received intensified adherence counselling and continued on first-line ART for 6 more months, after which participants who still had VL > 1000 copies/ml (Pragmatic VF) were switched to second line ART. VF rates were calculated and predictors of failure were found by fitting logistic regression and Cox proportional hazards models.ResultsThe 316 participants accrued 1036 person years at risk (pyar), 84 (26.6%) had conventional VF (rate 8.6 per 100 pyar) of whom 28 (33.3%) had pragmatic VF (rate 2.7 per 100 pyar). Independent predictors of conventional VF were; alcohol consumption, (adjusted Hazard Ratio; aHR = 1.71, 95% CI 1.05-2.79, P = 0.03) and ART adherence: per 10% decrease in proportion of adherent visits, (aHR = 1.83, 95% CI 1.50-2.23; P < 0.001). Using reference age group < 30 years, among conventional failures, the adjusted odds ratio (aOR) of pragmatic failure for age group 30-39 years were 0.12, 95% CI 0.03-0.57, P = 0.02 and for age group > 40 years were 0.14, 95%CI 0.03-0.71, P = 0.02. Alcohol consumers had a threefold odds of pragmatic failure than non-alcohol consumers (aOR = 3.14, 95%CI 0.95-10.34, P = 0.06).ConclusionA pragmatic VF approach is essential to guide switching to second line ART. Patient tailored ART adherence counselling among young patients and alcohol users is recommended.

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.

Trends of HIV Viral Load in Patients under Combined Antiretroviral Treatment in Bangui, Central African Republic

Background: The success of antiretroviral therapy requires better virological monitoring. We described the virological profile of patients on combined antiretroviral therapy (cART) for HIV/AIDS in Bangui, Central African Republic (CAR). Methods: In this prospective cohort study of patients who had been on combined antiretroviral therapy treatment (cART) for at least 12 months in Bangui, only one HIV plasma viral load per patient was realized at the Institut Pasteur of Bangui, between April 4th and November 28th, 2017. Sociodemographic and biological data were collected. Blood samples were taken for viral load. The biocentric generic human immunodeficiency virus (HIV) load test was used to quantify a ribonucleic acid (RNA) HIV-1. Data were analyzed with Stata software version 14. Chi-squared test was used to analyse viral load according to sex and age. The level of significance was set at P ≤ 0.05. Results: A total of 3569 patients were recruited, with a mean age of 40 years (median, 42 years; range, 1 - 84), patients aged 40 - 49 predominating (34.2%). The sex ratio was 0.4. No virus was detectable in plasma from 49.2% of patients, while 42.4% had virological failure (viral load, ≥1000 copies/mL) according to WHO criteria. The risk for virological failure decreased with age (P = 0.001) and was higher among females than males (P = 0.001). Conclusions: The rate of virological failure among patients on cART is very high in the CAR, despite the availability of and access to monitoring of HIV plasma viral load in Bangui. Therefore, adherence to treatment should be evaluated and reinforced in Bangui, CAR.

Cost–effectiveness of initial antiretroviral treatment administered as single vs. multiple tablet regimens with the same or different components

ObjectiveTo evaluate the efficiency of single-tablet regimens (STR) and multiple-tablet regimens (MTR) with exactly the same or different components. MethodsA study was conducted on HIV-1-infected antiretroviral-naïve patients from 6 Spanish or French centers, who were started on treatment with STR-Atripla®, or the same components separately (MTR-SC), or a different MTR (MTR-Other). Effectiveness was measured as percentage of HIV-RNA <50copies/mL at 48 weeks (ITT). Efficiency was the ratio between costs (direct cost of antiretrovirals plus outpatient visits, hospital admissions, and resistance tests) and effectiveness. ResultsThe study included a total of 2773 patients (759 STR-Atripla®, 483 MTR-SC, and 1531 MTR-Other). Median age was 37 years, 15% were HCV co-infected, 27% had a CD4+ count <200cells/μL, and 30% had viral load ≥100.000copies/mL. The duration of the assigned treatment was longer for STR-Atripla® (P<.0001). Response rates (adjusted for CD4+ count, viral load, and clustered on hospitals) at 48 weeks were 76%, 74%, and 62%, respectively (P<.0001). Virological failure was more common in MTR patients (P=.0025), and interruptions due to intolerance with MTR-Other (P<.0001). Cost per responder at 48 weeks (efficiency) was €12,406 with STR-Atripla®, €11,034 with MTR-SC (0.89 [0.82, 0.99] times lower), and €18,353 (1.48 [1.38, 1.61] times higher) with MTR-Other. ConclusionsSTR-Atripla® and MTR-SC regimens showed similar effectiveness, but virological failure rate was lower with STR-Atripla. MTR-SC, considered less convenient, had a marginally better efficiency, mainly due to lower direct costs. MTR-Other regimens had both a worse effectiveness and efficiency. Similar efficiency analyses adjusting for baseline characteristics should be recommended for new STRs.

High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.

Background:There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses.Methods:We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history). Plasma viral loads (PVL) are performed 6 months post-initiation and annually thereafter. Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9 years) while median duration of ART prior to switching to MVC was 13 years. Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1 Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and sustained it for 2.3 years. Median CD4 count change from baseline was +117 (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months respectively. Repeat tropism among patients with virologic failure demonstrated R5 virus.Conclusions:High rates of virologic failure was seen when MVC was used amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow up visit.Results:Data on 13 PLHIV were analyze

English

The benefits of antiretroviral therapy (ART) in patients living with HIV (PLWH) in Nepal have been obvious. However, their viral load (VL) and the effects of VL testing scale-up on the outcomes of HIV treatment have not been adequately investigated. In Nepal, VL tests were performed since 2009 at National Public Health laboratory. VL testing for monitoring scale up was introduced in 2014. The present study was undertaken to find out the virological failure (VF) and virological suppression (VS) rates in PLWH on ART in Nepal and to assess the effect of VL testing coverage on ART outcomes. A total of 8,230 blood/plasma samples were collected from among 11,922 patients on ART during 2009 to 2015. The VL testing coverage in 2009 was 2.9% which increased to 48.3% in 2015. VF was 35.9% in 2009 (mean for 2009-2013 was 27.5% and for 2014-2015 the mean VF was 10.2%).&nbsp; Decrease in VF to nearly one third in 2015 coincided with the rise in VL testing coverage (from 2.9 to 48.3%). Improvement in VL testing coverage for ART monitoring coincided with decline in VF, indicative of ART optimization. VL testing of ART treatment failure cases only in the first segment of the study (2009-2013), accounted for initial low VL coverage. However, 48.3% coverage in the last year of scale-up period, with a mean VF of 10.2% and nearly 90% of all those receiving ART having VS, was very encouraging.&nbsp; &nbsp; &nbsp; &nbsp;&nbsp; Key words:&nbsp; Viral load testing, Nepal, outcomes.

Long-term efficacy evaluation of antiretroviral therapy and genotypic resistance analysis among human immunodeficiency virus 1-infected children in Yunnan

Objective To evaluate the long-term efficacy of antiretroviral therapy and drug resistance among human immunodeficiency virus-1 (HIV-1)-infected children in Yunnan. Methods In this retrospective study, CD4+ T cell counts, HIV viral loads and genetic drug resistance results were obtained from HIV-1-infected children who were treated with antiretroviral treatment between January 2004 to July 2015. Results A total of 1 078 HIV/acquired immune deficiency syndrome (AIDS) children were treated with antiviral therapy. Before treatment, the average CD4+ cell number was (466.8±397.2) cells/μL. The percentages of children with CD4+ cell count >750 cells/μL after 1-year, 3-year, 5-year and 8-year treatment were 54.31%, 62.87%, 68.46% and 74.19%, respectively. Virological failure occurred in 150 HIV/AIDS children (13.9%), and the virological failure rate was 4.3/100 child-years. Among those 150 patients with virological failure, 104 cases (69.33%) exhibited genetic resistance to antiretroviral drugs. The prevalent mutations associated with drug resistance were M184V/I (75.0% [78/104]), K103N (43.3% [45/104]), G190A (29.8% [31/104]), Y181C (22.1% [23/104]), T215Y/F (20.2% [21/104]). Conclusions After long-term antiretroviral treatment, most of the HIV-infected children have restored the immunity and suppressed HIV viral replication successfully. HIV resistance is the main cause of virological failure. Drug resistance mutations mainly occur in nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor, and the resistance rate of proteinase inhibitor is low. Early genetic resistance testing and switch to second-line therapy will improve the treatment outcome. Key words: Child; Treatment outcome; Drug resistance; Antiretroviral treatment

Resistance analysis in patients with genotype 1–6 HCV infection treated with sofosbuvir/velpatasvir in the phase III studies

The fixed-dose combination of sofosbuvir/velpatasvir was highly efficacious in patients infected with genotype (GT)1-6 hepatitis C virus (HCV) in the ASTRAL studies. This analysis evaluated the impact of baseline resistance-associated substitutions (RASs) on treatment outcome and emergence of RASs in patients infected with HCV GT1-6 who were treated with sofosbuvir/velpatasvir. Non-structural protein 5A and 5B (NS5A and NS5B) deep sequencing was performed at baseline and at the time of relapse for all patients treated with sofosbuvir/velpatasvir for 12 weeks (n = 1,778) in the ASTRAL-1-3, ASTRAL-5 and POLARIS-2-3 studies. Patients with 37 known and 19 novel HCV subtypes were included in these analyses. Overall, 28% (range 9% to 61% depending on genotype) had detectable NS5A class RASs at baseline, using a 15% sequencing assay cut-off. There was no significant effect of baseline NS5A class RASs on sustained virologic response at week 12 (SVR12) with sofosbuvir/velpatasvir; the SVR12 rate in the presence of NS5A class RASs was 100% and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in patients with GT2 and GT4-6 infections. In GT3 infection, the SVR rate was 93% and 98% in patients with and without baseline NS5A class RASs, respectively. The overall virologic failure rate was low (20/1,778 = 1.1%) in patients treated with sofosbuvir/velpatasvir. Single NS5A class resistance was observed at virologic failure in 17 of the 20 patients. Sofosbuvir/velpatasvir taken for 12 weeks once daily resulted in high SVR rates in patients infected with GT1-6 HCV, irrespective of baseline NS5A RASs. NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients. Sofosbuvir/velpatasvir taken once daily for 12 weeks resulted in high sustained virologic response rates in patients infected with HCV, irrespective of the presence of NS5A resistance-associated variants prior to treatment. Single class NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients.

The treatment outcomes of antiretroviral substitutions in routine clinical settings in Asia; data from the TREAT Asia HIV Observational Database (TAHOD).

IntroductionAlthough substitutions of antiretroviral regimen are generally safe, most data on substitutions are based on results from clinical trials. The objective of this study was to evaluate the treatment outcomes of substituting antiretroviral regimen in virologically suppressed HIV‐infected patients in non‐clinical trial settings in Asian countries.MethodsThe study population consisted of HIV‐infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD). Individuals were included in this analysis if they started combination antiretroviral treatment (cART) after 2002, were being treated at a centre that documented a median rate of viral load monitoring ≥0.8 tests/patient/year among TAHOD enrolees, and experienced a minor or major treatment substitution while on virally suppressive cART. The primary endpoint to evaluate outcomes was clinical or virological failure (VF), followed by an ART class change. Clinical failure was defined as death or an AIDS diagnosis. VF was defined as confirmed viral load measurements ≥400 copies/mL followed by an ART class change within six months. Minor regimen substitutions were defined as within‐class changes and major regimen substitutions were defined as changes to a drug class. The patterns of substitutions and rate of clinical or VF after substitutions were analyzed.ResultsOf 3994 adults who started ART after 2002, 3119 (78.1%) had at least one period of virological suppression. Among these, 1170 (37.5%) underwent a minor regimen substitution, and 296 (9.5%) underwent a major regimen substitution during suppression. The rates of clinical or VF were 1.48/100 person years (95% CI 1.14 to 1.91) in the minor substitution group, 2.85/100 person years (95% CI 1.88 to 4.33) in the major substitution group and 2.53/100 person years (95% CI 2.20 to 2.92) among patients that did not undergo a treatment substitution.ConclusionsThe rate of clinical or VF was low in both major and minor substitution groups, showing that regimen substitution is generally effective in non‐clinical trial settings in Asian countries.