Virological Non-suppression Research Articles

Third Line Antiretroviral Treatment in India: Cohort Analysis and Treatment Outcomes from a Public Health Facility.

The National Programme in India provides free third-line antiretroviral treatment (ART) for all people living with HIV (PLHIV). Data of 232 PLHIV initiated on third-line ART from a single center in New Delhi were retrospectively analyzed for virological suppression at 6 and 12 months, factors predicting nonresponse, retention in care, and mortality from June 2016 till December 2019. The mean age at third-line ART initiation was 39.54 ± 11.08 years, 71.5% were males, and 55.02% had HIV duration of >10 years. The mean CD4 count at third-line ART initiation was 260.04 ± 200.4/mm3, and the median viral load (VL) at second-line failure was 61,253 copies/mL (interquartile range, 12,599-315,497 copies/mL). Of the patients, 71.52% achieved virological suppression at 6 months (n = 151), and this was maintained at 12 months-72% (n = 50). The mortality rate among those still in active care was 8.69% (18/207). PLHIV who did not attain virological suppression at 6 months had significantly shorter duration on second-line ART (p = 0.0002), lower peak CD4 achieved on second-line ART (p = 0.039), higher VL at second-line failure (p = 0.012), and lower body weight (p < 0.0001). On univariate analysis, lower CD4 peak on second-line ART (p = 0.019), lower CD4 count at third-line ART initiation (p = 0.004), and lower body weight (p = 0.0002) were significantly predictive of virological nonsuppression at 6 months. Successful implementation of a third-line ART program can indeed be done through a public health approach. Intensive adherence support, nutritional rehabilitation, and regular viral load monitoring are crucial for improved clinical and virological outcomes.

High rate of loss to follow-up and virological non-suppression in HIV-infected children on antiretroviral therapy highlights the need to improve quality of care in South Africa.

Provision of high-quality care and ensuring retention of children on antiretroviral therapy (ART) are essential to reduce human immunodeficiency virus (HIV)-associated morbidity and mortality. Virological non-suppression (≥1000 viral copies/ml) is an indication of suboptimal HIV care and support. This retrospective cohort study included ART-naïve children who initiated first-line ART between July 2015 and August 2017 in Johannesburg and rural Mopani district. Of 2739 children started on ART, 29.5% (807/2739) were lost to care at the point of analysis in August 2018. Among retained children, overall virological non-suppression was 30.2% (469/1554). Virological non-suppression was associated with higher loss to care 30.3% (229/755) compared with suppressed children (9.7%, 136/1399, P < 0.001). Receiving treatment in Mopani was associated with virological non-suppression in children under 5 years (adjusted odds ratio (aOR) 1.7 (95% confidence interval (CI) 1.1-2.4), 5-9 years (aOR 1.8 (1.1-3.0)) and 10-14 years (aOR 1.9 (1.2-2.8)). Virological non-suppression was associated with lower CD4 count in children 5-9 years (aOR 2.1 (1.1-4.1)) and 10-14 years (aOR 2.1 (1.2-3.8)). Additional factors included a shorter time on ART (<5 years aOR 1.8-3.7 (1.3-8.2)), and male gender (5-9 years, aOR1.5 (1.01-2.3)), and receiving cotrimoxazole prophylaxis (10-14 years aOR 2.0 (1.2-3.6)). In conclusion, virological non-suppression is a factor of subsequent programme loss in both regions, and factors affecting the quality of care need to be addressed to achieve the third UNAIDS 90 in paediatric HIV.

Tenofovir resistance in early and long-term treated patients on first-line antiretroviral therapy in eight low-income and middle-income countries.

We aimed to assess the frequency of tenofovir (TDF) resistance in people failing tenofovir/lamivudine or emtricitabine (XTC)/nonnucleotide reverse-transcriptase inhibitor-based first-line antiretroviral treatment (ART) using data from 15 nationally representative surveys of HIV drug resistance conducted between 2014 and 2018 in Cameroon, Guatemala, Honduras, Nicaragua, Senegal, Uganda, Vietnam and Zambia. Prevalence of nucleoside reverse-transcriptase inhibitor resistance among participants with virological nonsuppression (viral load ≥1000 copies/ml) who had received TDF-based ART for 12-24 months (early ART group) and at least 40 months (long-term ART group) was assessed using Sanger sequencing and resistance was interpreted using the Stanford HIVdb algorithm. For each group, we estimated a pooled prevalence using random effect meta-analysis. Of 4677 participants enrolled in the surveys, 640 (13.7%) had virological nonsuppression, 431 (67.3%) were successfully genotyped and were included in the analysis; of those, 60.3% (260) were participants in the early ART group. Overall, 39.1, 57.9, 38.5 and 3.6% patients in the early ART group and 42.9, 69.3, 42.9 and 10.0% patients on long-term ART had resistance to TDF, XTC, TDF + XTC and TDF + XTC + zidovudine, respectively. Overall, tenofovir resistance was mainly due to K65R or K70E/G/N/A/S/T/Y115F mutations (79%) but also due to thymidine analogue mutations (21%) which arise from exposure to thymidine analogues but causing cross-resistance to TDF. Dual resistance to TDF + XTC occurred in more than 40% of the people with viral nonsuppression receiving tenofovir-based first-line ART, supporting WHO recommendation to optimize the nucleoside backbone in second-line treatment and cautioning against single drug substitutions in people with unsuppressed viral load.

High Levels of Acquired HIV Drug Resistance Following Virological Nonsuppression in HIV-Infected Women from a High-Risk Cohort in Uganda.

HIV drug resistance (HIVDR) is of increasing health concern, especially among key populations. We investigated the prevalence of virological suppression (VS), prevalence and correlates of HIVDR in HIV-infected women, enrolled in a high-risk cohort. We enrolled 267 women initiated on first-line antiretroviral therapy (ART) between 2015 and 2018. Participants' plasma samples were analyzed for HIV RNA viral load (VL) and genotypic resistance testing was performed on those with VL nonsuppression (defined as VL ≥1,000 copies/mL). We used the Stanford HIVDR database-algorithm to assess HIVDR mutations and logistic regression to assess risk factors for VL nonsuppression and HIVDR. We observed an overall VS prevalence of 76.0% (203/267) and detected respective acquired drug resistance prevalence to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) of 81.3% [confidence interval (CI) 67.4-91.1] and 45.8% (CI 31.4-60.8) among the 48 successfully genotyped VL nonsuppressors. NNRTI mutations were observed in 81.3% (39/48) of the genotyped participants and 45.8% (22/48) had both NRTI and NNRTI mutations. The mutation K103N was detected in 62.5% (30/48) of participants, 41.7% (20/48) had M184V/I, 14.6% had K65R, and 12.5% (6/48) had thymidine analog mutations (TAMs). None of the analyzed potential risk factors, including age and duration on ART, was significantly correlated with VL nonsuppression or HIVDR. Although high levels of NNRTI mutations support the transition to dolutegravir, the presence of NRTI mutations, especially TAMs, may compromise dolutegravir-based regimens or other second-line ART options. The moderate VS prevalence and high HIVDR prevalence therefore call for timely ART switching and intensive adherence counseling.

HIV virological non-suppression and factors associated with non-suppression among adolescents and adults on antiretroviral therapy in northern Ethiopia: a retrospective study

BackgroundDespite the benefits of Antiretroviral Therapy (ART), there is a growing concern of treatment failure. This study aimed to assess viral non suppression rate and factors associated with HIV viral non suppression among adolescents and adults on ART in Northern Ethiopia.MethodsA retrospective cross sectional study was done on 19,525 study subjects. All the data in the database of Tigray Health Research Institute was exported to Microsoft excel 2010 and then data verification and filtration were done before exporting to STATA 14.0 for analysis. Generalized Estimating Equation (GEE) logistic regression was used for statistical modeling of viral non suppression.ResultsA total of 5153 (26.39%; 95%CI (25.77%, 27.02)) patients had no viral suppression despite being on ART. Being male (AOR = 1.27, 95% CI: 1.18, 1.37), 15–19 years of age (AOR = 4.86, 95%CI: 3.86, 6.12), patients from primary hospital (AOR = 1.26, 95%CI: 1.05, 1.52), WHO staging II (AOR = 1.31, 95%CI: 1.10, 1.54), poor ART adherence level (AOR = 2.56, 95%CI: 1.97, 3.33), fair ART adherence level (AOR = 1.61, 95%CI: 1.36, 1.90), baseline CD-4 count of < 200 cells/micro liter (AOR = 1.33, 95%CI: 1.14, 1.54), recent CD-4 count of < 200 cells/micro liter (AOR = 3.78, 95%CI: 3.34, 4.27), regimen types: 1c (AZT-3TC-NVP) (AOR = 1.32, 95%CI: 1.22, 1.44), 2 h (TDF-3TC-ATV/R) (AOR = 1.79, 95%CI: 1.27, 2.52) and declined immunological responses after ART initiation (AOR = 1.45, 95%CI: 1.30, 1.61) were significantly associated with viral non-suppression.ConclusionsThe virological non suppression was high which makes it less likely to achieve the third 90 UNAIDS target. Being male, patients with WHO staging II and poor ART adherence level were significantly associated with viral non suppression. Therefore, intensive adherence support and counseling should be provided. It is also a high time to determine the antiretroviral drugs resistance pattern given the fact that a large number of patients had virological non suppression.

Respective roles of migration and social deprivation for virological non-suppression in HIV-infected adults on antiretroviral therapy in France.

Barriers to achieve sustained HIV virological suppression on antiretroviral therapy (ART) jeopardize the success of the 90:90:90 UNAIDS initiative which aims to end the HIV/AIDS epidemic. In France, where access to ART is free and universally available, we analyze the way in which social determinants of health (i.e. cultural, environmental) and economic factors might influence virological outcomes. A cross-sectional study was performed in two hospitals located in Paris area. All consecutive people living with HIV (PLHIV) on ART for at least 6 months attending the outpatient clinics between 01/05/2013 and 31/10/2014 answered an individual score of deprivation, EPICES, retrieving information on health insurance status, economic status, family support and leisure activity. This score varies from 0 to 100 with deprivation state defined above 30.17. Factors associated with HIV viral load >50 copies/ml were assessed by logistic regression modeling with a backward stepwise selection to select the final multivariable model. Sensitivity analyses were performed using two other thresholds for virological non-suppression (100 or 200 copies/ml). Overall, 475 PLHIV were included (53% male, median age 47 years, 66% not born in France mainly in a sub-Saharan African country). Half of French natives and 85% of migrants were classified as deprived. Median duration on ART was 9.7 years with virological suppression in 95.2% of non-deprived participants and in 83.5% of deprived ones (p = 0.001). The final multivariable model retained ART tiredness, younger age, a previous AIDS event and social deprivation (adjusted Odds Ratio, 2.9; 95%CI, 1.2–7.0) as determinants of virological non-suppression but not migration in itself. When using separate components of EPICES score, reporting economic difficulties and non-homeownership were associated with virological non-suppression. In addition to interventions focusing on cultural aspects of migration, social interventions are needed to help people with social vulnerability to obtain sustained responses on ART.

Virological Non-suppression and Its Correlates Among Adolescents and Young People Living with HIV in Southern Malawi.

We examined virological non-suppression (VLN) among youth ages 13-24years receiving HIV treatment in public health facilities in six southern Malawi districts. We also tested three ART adherence measures to determine how well each identified VLN: pill counts, a Likert scale item, and a visual analogue scale. VLN was defined as HIV RNA > 1000 copies/ml. Of the 209 youth, 81 (39%) were virally non-suppressed. Male gender and stigma were independently associated with VLN; social support and self-efficacy were independently protective. Pill count had the highest positive predictive value (66.3%). Using a pill count cut-off of < 80% nonadherence, 36 (17%) of the youth were non-adherent. Of the adherent, 120 (69%) were viral suppressed. Results indicate the need to address HIV-related stigma and to bolster social support and selfefficacy in order to enhance viral suppression. In the absence of viral load testing, pill count appears the most accurate means to assess VLN.

Factors Associated with Virological Non-suppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014\u2013July 2015

BackgroundDespite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non-suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non-suppression.MethodsWe conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression.ResultsThe study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non-suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of non-suppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5–7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0–3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0–4 years (ORadj = 5.3, 95%CI = 4.6–6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7–4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9–3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6–2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78–0.95) protected patients against virological non-suppression.ConclusionYoung age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.

Socioeconomic status and treatment outcomes for individuals with HIV on antiretroviral treatment in the UK: cross-sectional and longitudinal analyses

SummaryBackgroundFew studies have assessed the effect of socioeconomic status on HIV treatment outcomes in settings with universal access to health care. Here we aimed to investigate the association of socioeconomic factors with antiretroviral therapy (ART) non-adherence, virological non-suppression, and virological rebound, in HIV-positive people on ART in the UK.MethodsWe used data from the Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA) questionnaire study, which recruited participants aged 18 years or older with HIV from eight HIV outpatient clinics in the UK between Feb 1, 2011, and Dec 31, 2012. Participants self-completed a confidential questionnaire on sociodemographic, health, and lifestyle issues. In participants on ART, we assessed associations of financial hardship, employment, housing, and education with: self-reported ART non-adherence at the time of the questionnaire; virological non-suppression (viral load >50 copies per mL) at the time of questionnaire in those who started ART at least 6 months ago (cross-sectional analysis); and subsequent virological rebound (viral load >200 copies per mL) in those with initial viral load of 50 copies per mL or lower (longitudinal analysis).FindingsOf the 3258 people who completed the questionnaire, 2771 (85%) reported being on ART at the time of the questionnaire, and 2704 with complete data were included. 873 (32%) of 2704 participants reported non-adherence to ART and 219 (9%) of 2405 had virological non-suppression in cross-sectional analysis. Each of the four measures of lower socioeconomic status was strongly associated with non-adherence to ART, and with virological non-suppression (prevalence ratios [PR] adjusted for gender/sexual orientation, age, and ethnic origin: greatest financial hardship vs none 2·4, 95% CI 1·6–3·4; non-employment 2·0, 1·5–2·6; unstable housing vs homeowner 3·0, 1·9–4·6; non-university education 1·6, 1·2–2·2). 139 (8%) of 1740 individuals had subsequent virological rebound (rate=3·6/100 person-years). Low socioeconomic status was predictive of longitudinal rebound risk (adjusted hazard ratio [HR] for greatest financial hardship vs none 2·3, 95% CI 1·4–3·9; non-employment 3·0, 2·1–4·2; unstable housing vs homeowner 3·3, 1·8–6·1; non-university education 1·6, 1·1–2·3).InterpretationSocioeconomic disadvantage was strongly associated with poorer HIV treatment outcomes in this setting with universal health care. Adherence interventions and increased social support for those most at risk should be considered.FundingNational Institute for Health Research.

Plasma Efavirenz Exposure, Sex, and Age Predict Virological Response in HIV-Infected African Children.

Owing to insufficient evidence in children, target plasma concentrations of efavirenz are based on studies in adults. Our analysis aimed to evaluate the pediatric therapeutic thresholds and characterize the determinants of virological suppression in African children. We analyzed data from 128 African children (aged 1.7-13.5 years) treated with efavirenz, lamivudine, and one among abacavir, stavudine, or zidovudine, and followed up to 36 months. Individual pharmacokinetic (PK) measures [plasma concentration 12 hours after dose (C12h), plasma concentration 24 hours after dose (C24h), and area under the curve (AUC0-24)] were estimated using population PK modeling. Cox multiple failure regression and multivariable fractional polynomials were used to investigate the risks of unsuppressed viral load associated with efavirenz exposure and other factors among 106 initially treatment-naive children, and likelihood profiling was used to identify the most predictive PK thresholds. The risk of viral load >100 copies per milliliter decreased by 42% for every 2-fold increase in efavirenz mid-dose concentration [95% confidence interval (CI): 23% to 57%; P < 0.001]. The most predictive PK thresholds for increased risk of unsuppressed viral load were C12h 1.12 mg/L [hazard ratio (HR): 6.14; 95% CI: 2.64 to 14.27], C24h 0.65 mg/L (HR: 6.57; 95% CI: 2.86 to 15.10), and AUC0-24 28 mg·h/L (HR: 5.77; 95% CI: 2.28 to 14.58). Children older than 8 years had a more than 10-fold increased risk of virological nonsuppression (P = 0.005); among children younger than 8 years, boys had a 5.31 times higher risk than girls (P = 0.007). Central nervous system adverse events were infrequently reported. Our analysis suggests that the minimum target C24h and AUC0-24 could be lowered in children. Our findings should be confirmed in a prospective pediatric trial.

Socio-economic factors and virological suppression among people diagnosed with HIV in the United Kingdom: results from the ASTRA study.

IntroductionIn the United Kingdom, rates of virological suppression on antiretroviral therapy (ART) are very high, but there remain a small but significant number of people on ART with detectable viraemia. The impact of socio-economic factors on virological suppression has been little studied.Materials and MethodsWe used data from ASTRA, a cross-sectional, questionnaire study of >3000 individuals from 8 clinics in the United Kingdom in 2011–2012, linked to clinical records to address this question. Included participants had received ART for >6 months with a recorded current viral load (VL) (latest at the time of questionnaire). Participants provided data on demographic factors: gender, sexual orientation, ethnicity and age; and socio-economic factors: UK birth/English reading ability, employment, housing, education and financial hardship. To assess non-adherence, participants were asked if in the past 3 months, they had missed ART for ≥2 days at a time. Virological suppression was defined as VL≤50 cps/mL. For each socio-economic factor, we calculated prevalence ratios using modified Poisson regression, first adjusting for demographic factors, then also for non-adherence.ResultsA total of 2445 people fulfilled the inclusion criteria (80% male, 69% MSM, median age: 46 years, median CD4 count: 556 cells/mm3); 10% (234/2445) had VL>50 cps/mL. After adjusting for demographic factors, non-fluent English, not being employed, not home owning, education below university level and increasing financial hardship were each associated with higher prevalence of VL>50 cps/mL. Additional adjustment for non-adherence largely attenuated each association, but did not fully explain them (see Table 1). After adjustment for non-adherence and demographic factors, younger age was also associated with VL>50 cps/mL: for each additional 10 years an individual was 0.80 (95% CI 0.70–0.92) times as likely to have VL>50 cps/mL (p=0.0019). Adjusted prevalence ratios for VL>50cps/mL were 0.91 (0.62–1.34) for women and 1.25 (0.85–1.84) for non-MSM men versus MSM, and 1.29 (0.92–1.80) for white versus non-white people. ConclusionsAmong people on ART in the United Kingdom, the proportion with detectable VL is low. Poorer socio-economic status is associated with increased probability of virological non-suppression. It is likely that much of this association is mediated through difficulties in taking ART. Emphasis should be put on aiding the adherence of people in these higher risk groups.

Increasing Transfers-Out from an Antiretroviral Treatment Service in South Africa: Patient Characteristics and Rates of Virological Non-Suppression

ObjectivesTo determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township.MethodsThis retrospective cohort study included all patients aged ≥15 years who enrolled between September 2002 and December 2009. Follow-up data were censored in December 2010. Kaplan-Meier survival analysis was used to describe time to transfer-out and cox proportional hazard analysis was used to determine associated risk factors.Results4511 patients (4003 ART-naïve and 508 non-naïve at baseline) received ART during the study period. Overall, 597 (13.2%) transferred out. The probability of transferring out by one year of ART steadily increased from 1.4% in 2002/2004 cohort to 8.9% for the 2009 cohort. Independent risk factors for transfer-out were more recent calendar year of enrolment, younger age (≤25 years) and being ART non-naïve at baseline (i.e., having previously transferred into this clinic from another facility). The proportions of patients transferred out who had a CD4 cell count <200 cells/µL and/or a viral load ≥1000 copies/mL were 19% and 20%, respectively.ConclusionsWith scale-up of ART over time, an increasing proportion of patients are transferring between ART services and information systems are needed to track patients. Approximately one-fifth of these have viral loads >1000 copies/mL around the time of transfer, suggesting the need for careful adherence counseling and assessment of medication supplies among those planning transfer.