Risk Factors For Virological Failure Research Articles

HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre study (DTG RESIST)

IntroductionHIV drug resistance poses a challenge to the United Nation’s goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was...

HIV-1 subtype-specific drug resistance on dolutegravir-based antiretroviral therapy: protocol for a multicentre longitudinal study (DTG RESIST).

HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the World Health Organization in 2019 for first-, second-, and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance. DTG RESIST is a multicentre longitudinal study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virologic failure on dolutegravir-based ART. At the time of virologic failure whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (i) individuals who experienced virologic failure on dolutegravir, and (ii) on those who started or switched to such a regimen and were at risk of virologic failure. For population (i), the outcome will be any InSTI drug resistance mutations, and for population (ii) virologic failure defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virologic failure and limited power for analysing factors associated with individual InSTI drug resistance mutations. The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa, and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in IeDEA and have obtained ethics approval from their local ethics committee to conduct the additional data collection. NCT06285110. - DTG RESIST is a large international study to prospectively examine emergent dolutegravir resistance in diverse settings characterised by different HIV-1 subtypes, provision of ART, and guidelines on resistance testing. - Embedded within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST will benefit from harmonized clinical data across participating sites and expertise in clinical, epidemiological, biological, and computational fields. - Procedures for sequencing and assembling genomes from different HIV-1 strains will be developed at the heart of the HIV epidemic, by the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), in Durban, South Africa. Phenotypic testing, Genome Wide Association Study (GWAS) methods and Bayesian evolutionary models will explore and predict treatment failure genotypes. - A significant limitation is the absence of genotypic resistance data from participants before they started dolutegravir treatment, as collecting and bio-banking pre-treatment samples was not feasible at most IeDEA sites. Consistent and harmonized data on adherence to treatment are also lacking. - The distribution of HIV-1 subtypes across different sites is uncertain, which may limit the statistical power of the study in analysing patterns and risk factors for dolutegravir resistance. The results from GWAS and Bayesian modelling analyses will be preliminary and hypothesis-generating.

Predictors of antiretroviral treatment failure to the first line therapy: a cross-sectional study among Iranian HIV-positive adults

BackgroundHIV virological failure is one of the main problems in HIV-infected patients, and identifying the main predictors of such treatment failure may help in combating HIV/AIDS.MethodologyThis cross-sectional study included 1800 HIV-infected patients with either virological failure or treatment response. HIV viral load, CD4 count, and other tests were performed. Statistical analysis was used to determine the predictors of virological failure.ResultsClinical stage, treatment with reverse transcriptase inhibitors (RTIs), under therapy for three years or more, suboptimal adherence to antiretroviral treatment (ART), age > 40 years, CD4 count < 200 cells/mm3, unemployment, being infected through sex, and the presence of symptoms were the predominant risk factors for virological failure. In addition, 55% of patients who experienced virological failure failed to experience immunological and/or clinical failure.ConclusionAs the first study in southern Iran and the second in Iran, Iranian policymakers should focus on intensive counseling and adherence support and emphasize more effective treatment regimens such as protease and integrase inhibitors (PIs and INTIs), to increase the chance of a treatment response to ART. The accuracy of identifying clinical and immunological criteria in resource-limited settings is not promising. The present findings can be used to determine effective measures to control HIV treatment failure and design efficient strategies for the ambitious 95–95–95 plan.

Determinants of viral load suppression failure among HIV adults on ARV attending health care facilities: a retrospective study in Tanga region, Tanzania

BackgroundAvailability and accessibility of Antiretroviral drugs (ARV’s) improve the lives of People living with HIV (PLHIV) by improving client’s immune system to overcome infections and prevent the development of AIDS and other HIV complications. Combination therapy, early initiation of ART, newer ART drugs, single dosage and drug affordability significantly contribute in the reduction of viral multiplication and suppression of HIV to undetectable plasma levels.MethodsA retrospective longitudinal study design study was conducted from 1st October, 2018 to 30th June 2022 in all supported HIV care and treatment health facilities in Tanga region which were supported by Amref Health Africa, Tanzania. The participants were HIV adult patients aged 15 years and above on ART and attended the clinic at least once after ART initiation. Viral load suppression levels are defined with viral load <1,000 HIV RNA copies/ml (viral load suppression). Cox proportional hazard regression models were employed to identify risk factors for virological failure. P values were two-sided, and we considered a P<0.05 to be statistically significant.ResultsFifty-nine thousand five hundred three adult clients >15 years whom were on ART were included in the analysis to determine the level of plasma Viral Load suppression after being on ART. Female 41,304 (69.4%) and male 18,199 (30.6%). Only four percent (2,290) were found to be unsuppressed i.e having plasma Viral Load >1,000cp/ml while 96% (57,213) were virally suppressed. Several factors were independently associated with virologic failure that included; age between 15 - <25 years (HR: 2.82, 95% CI 1.96 – 4.04), BMI <18.5 (HR: 1.69, 95% CI 1.23 – 2.30), advanced WHO stage IV (HR: 1.60, 95% CI 1.12 – 2.24), CD4 cell count <350 (HR: 2.61, 95% CI 2.12 – 3.23), poor adherence (HR: 1.98, 95% CI 1.80 – 2.18) and not using DTG based drug (HR: 11.8, 95% CI 9.74 – 14.3).ConclusionVirologic failure was observed in this study among clients with young age, advanced WHO stage IV, not using DTG based regimen, poor drug adherence and second line regime. To improve Viral Load Suppression among these clients; the existing HIV intervention strategies should be taken care by targeting the identified risk factors.

HIV. Long-acting treatment : clinical experience, limits and future perspectives

In this article, we first present the current administration criteria, the risk factors for virological failure, and our practical experience with the first long-acting injectable HIV treatment available in Switzerland (the combination of cabotegravir/rilpivirine). We then discuss the theoretical and practical potential, as illustrated by an innovative study in San Francisco, provided by administering long-acting treatment outside the current criteria. This approach could notably offer antiretroviral treatment to particularly vulnerable populations for whom oral antiretroviral therapy is sometimes challenging. Finally, we touch upon the future drug prospects of long-acting treatments under study for HIV.

High risk of virologic failure among HIV-infected children and adolescents routinely followed-up in Littoral region of Cameroon.

Virological response to antiretroviral therapy (ART) remains a challenge for HIV-infected children and adolescents due to non-optimization of pediatric ART for resource-limited settings. In this study, we aimed to investigate factors associated with virologic failure (VF) in HIV-infected-children and adolescents on ART in Cameroon. A prospective patient-based cohort study was conducted among HIV-infected children (0-9 years) and adolescents (10-19 years) followed-up between November 2018 and October 2019 in 38 healthcare centers located in the Littoral region of Cameroon. The 1st viral load (VL) was assessed after 6 months of ART initiation and the 2nd VL between 3 and 6 six months later in patients with VL ≥1000 copies/ml in accordance with the national algorithm using Abbott Real-Time HIV-1 Viral Load Assay. Multivariate analyses were performed to identify the determinants of higher risk of VF. Of 1,029 HIV-infected children and adolescents (393 children and 636 adolescents), 801 (77.8%) cumulatively presented with VL <1000 copies/mL within 12 months on ART. Adolescents were more likely to have VF than children (24.5% vs 18.3%, OR: 1.39; 95%CI: 1.00-1.93; p = 0.047). Patients followed-up in decentralized care units were significantly more likely to have VF compared to those attending the accredited treatment centers (26.1% vs 16.6%, OR: 1.88, 95%CI: 1.37-2.58; p<0.001). Our findings show a high rate of VL suppression (VLS, 77.8%) among HIV-infected children and adolescents, albeit lower than the established target of 90%. Being adolescent and patients followed in the decentralized care units are high risk factors for VF, thereby necessitating routine therapeutic education of patients and guardians in resource limited countries to improve VLS.

Long-Term Virological Treatment Outcomes in Adolescents and Young Adults With Perinatally and Non-Perinatally Acquired Human Immunodeficiency Virus

Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18-24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands. We included individuals registered in the national ATHENA observational cohort from 2000 until 2020 who had entered care before the age of 25 years, who had received ART for at least 6 months with at least 2 available HIV ribonucleic acid measurements between the age of 18 and 24 years. We compared VF between age groups 12-17, 18-24, and 25-30 years. A multivariable generalized linear mixed model was used to evaluate risk factors for VF. Analyses were stratified by HIV acquisition mode. In total, 1174 non-perinatally PWH and 157 perinatally PWH were included. In 2020, VF rate was 7% in non-perinatally PWH young adults and 19% in perinatally PWH young adults. The adjusted risk for VF was significantly higher in those aged 18-24 compared to 25-30 years in both non-perinatally PWH (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.07-1.50) and perinatally PWH (OR, 2.34; 95% CI, 1.48-3.71). Young adulthood is a vulnerable period, with increased risk for VF, especially for perinatally PWH. The probability of VF decreased over time, but less for perinatally PWH compared to non-perinatally PWH.

Outcomes of persistent low-level viremia among HIV patients on antiretroviral therapy: A prospective cohort study.

We aimed to investigate the relationship between low-level viremia (LLV) and virological failure (VF), death, and non-AIDS events (NAEs). A prospective cohort study of people living with HIV (PLHIV) on antiretroviral therapy (ART) was conducted from 2011-2018 at an HIV clinic in Shenyang, China. The incidence of VF and the mortality and NAEs due to LLV were assessed. Cox proportional hazards regression was performed to investigate risk factors for VF, mortality, and NAEs. In total, 1288 patients, contributing 3915 person-years of follow-up (median follow-up, 2.5years [interquartile range: 2-4years]), were enrolled. Thirty-one patients (2.4%) experienced VF, 5 (0.4%) died, and 38 (3.0%) experienced NAEs. The risk of VF was significantly increased among patients with a viral load (VL) of 200-499 copies/mL (adjusted hazard ratio [aHR]: 14.92, 95% confidence interval [CI]: 5.92-37.60) or 500-999 copies/mL (aHR: 13.68, 95% CI: 3.61-51.87), but not among patients with a VL of 50-199 copies/mL (aHR: 3.10, 95% CI: 0.86-11.09). The risk of NAEs was significantly increased among patients with LLV (aHR: 7.33, 95% CI: 3.73-14.42). Compared to no LLV, a VL of 50-199 copies/mL (aHR: 4.11, 95% CI: 1.73-9.74), 200-499 copies/mL (aHR: 18.31, 95% CI: 6.66-50.33), and 500-999 copies/mL (aHR: 21.34, 95% CI: 5.69-80.01) showed higher risk of NAEs. Low-level viremia was associated with VF and NAEs. Patients with LLV, especially those with a VL ≥200 copies/mL, may need more frequent VL testing and NAE screening.

Determinants of viral load non-suppression among people living with HIV on antiretroviral therapy in Kumasi, Ghana

Objectives: To determine the rate and factors associated with viral load non-suppression among adults living with HIV/AIDS on active anti-retroviral therapy (ART).Design: A retrospective cross-sectional studySetting: Three ART clinics in Kumasi, GhanaParticipants: All HIV-infected adults who were ≥18 years and on active ART for 12 months and whose viral loadnhad been estimated were included.Main outcome measure: Unsuppressed viral load among patients on ARTResults: In all, 483 HIV patients were included in the study, with 369 (76.4%) achieving viral load suppression. Gender, educational level, comorbidity status, and duration on ART were independently associated with viral nonsuppression (p &lt; 0.05).Conclusions: This study has revealed that the rate of viral suppression in the study area is lower than the UNAIDS 90% target. The findings have implications on designing new and stemming up implementation of existing interventions to improve the rate of viral suppression among patients in the study area. It is also necessary that more of such studies are replicated in other parts of the country to identify risk factors for virological failure among patients on ART.

Clinical, Immunological, and Virological Outcomes Among Youths With Perinatal HIV After Transition to Adult Units in Spain From 1997 to 2016.

Children living with HIV are reaching adulthood and transitioning to adult clinics. This study aimed to describe clinical and immunovirological status after transition in patients with perinatal HIV. Patients participating in the Spanish multicenter pediatric HIV cohort (CoRISpe) transferred to adult care (FARO cohort) from 1997 to 2016 were included. Clinical and immunovirological data were collected from 12 years old to the last follow-up moment after transition (up to December 2017). We used mixed-effect models to analyze changes in CD4 counts or viral suppression and multivariate analysis for risk factors for virological failure (VF) and immune status after transition. Transition years were classified into 5-year periods. Three hundred thirty-two youths were included. The median age at transition was 18 years (interquartile range: 16.3-18.9) and 58.1% women. The median follow-up time after transition was 6.6 years (interquartile range: 4.6-9.8), and 11 patients (3.3%) died. The immunovirological status at transition improved over the last periods. Globally, VF decreased from 27.7% at transition to 14.4% at 3 years post-transition (P < 0.001), but no changes were observed in the last 2 transition periods. There were no significant differences in CD4 over the transition period. Risk factors for VF after transition were female sex, being born abroad and VF at transition, and for lower CD4 after transition were Romani heritage, younger age at transition, lower CD4 nadir, and CD4 at transition. After transition, virological suppression improved in the early transition periods, and immunological status remained stable. Nevertheless, some patients had higher risk of worse outcomes. Identifying these patients may aid during transition.

High turnaround times and low viral resuppression rates after reinforced adherence counselling following a confirmed virological failure diagnostic algorithm in HIV-infected patients on first-line antiretroviral therapy from Tanzania.

Early identification of confirmed virological failure is paramount to avoid accumulation of drug resistance in patients on antiretroviral therapy (ART). Scale-up of HIV-RNA monitoring in Africa and timely switch to second-line regimens are challenged. A WHO adapted confirmed virological treatment screening algorithm (HIV-RNA screening, enhanced adherence counselling, confirmatory HIV-RNA testing) was evaluated in HIV-infected patients on first-line ART from Tanzania. The main endpoints included viral resuppression and virological failure rates, retention and turnaround time of the screening algorithm until second-line ART initiation. Secondary endpoints included risk factors for virological treatment failure and patterns of genotypic drug resistance. HIV-RNA >1000 copies/ml at first screening was detected in 58/356 (16.3%) patients (median time-on-treatment 6.3years, 25% immunological treatment failure). Adjusted risk factors for virological failure were age <30years (RR 5.2 [95% CI: 2.5-10.8]), years on ART ≥3years (RR 3.0 [1.0-8.9]), CD4-counts <200 cells/µl (RR 9.3 [4.0-21.8]) and poor self-reported treatment adherence (RR 2.0 [1.2-3.4]). Resuppression of HIV-RNA <1000 copies/ml was observed in 5/50 (10%) cases after enhanced adherence counselling. Confirmatory testing within 3months was performed in only 46.6% and switch to second-line ART within 6months in 60.4% of patients. Major NNRTI-mutation were detected in all of 30 patients, NRTI mutations in 96.7% and ≥3 thymidine-analogue mutations in 40%. No remaining NRTI options were predicted in 57% and limited susceptibility in 23% of patients. We observed low levels of viral resuppression following adherence counselling, associated with high levels of accumulated drug resistance. High visit burden and turnaround times for confirmed virological failure diagnosis further delayed switching to second-line treatment which could be improved using novel point-of-care viral load monitoring systems.

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.

Longitudinal virological outcomes and factors associated with virological failure in behaviorally HIV-infected young adults on combination antiretroviral treatment in the Netherlands, 2000 to 2015.

Achieving and maintaining viral suppression in young adults (18–24 years) living with HIV is challenging. Overall HIV viral suppression rates are lower in young as compared to older adults. Longitudinal data provide valuable insight on dynamics of viral suppression and variables of potential influence on HIV virological failure (VF), but is scarce in young adults living with HIV on combination antiretroviral therapy (cART). We evaluated longitudinal virological outcomes of behaviorally young adults (18–24 years) living with HIV in the Netherlands over a period of 15 years.We analyzed data from the Dutch national HIV database of 816 young adults living with HIV on cART in the Netherlands from 2000 to 2015. VF was defined as 2 consecutive detectable plasma HIV-1 viral load (VL) measurements > 200 copies/ml. Generalized linear mixed model analyses were used to assess HIV VF over time and identify risk factors associated with VF.VF during the study follow-up occurred at least once in 26% of cases. The probability of experiencing VF decreased over the study period per calendar year (OR 0.78, 95% confidence interval [CI];0.72; 0.85). Factors significantly associated with VF were being infected through heterosexual contact (OR 5.20, CI 1.39;19.38) and originating from Latin America or the Caribbean (OR 6.59, CI 2.08;20.92). Smaller, yet significant risk factors for VF were being infected through a blood transfusion or a needle accident (OR9.93, CI 1.34;73.84, and having started with cART with a nadir CD4 count >500 cells/μl (OR 11.36, CI 2.03;63.48).In our large cohort of young adults, the risk of VF has diminished over 15 years. Specific subgroups were identified to be at risk for suboptimal treatment.

First-line antiretroviral treatment and virological response among HIV adult patients at an accredited HIV care center, Cameroon

BackgroundViral load (VL) monitoring in the clinical follow-up of HIV patients to detect treatment failure is not routinely offered in Cameroon. The study was designed to characterize virological response on antiretroviral treatment (ART) among adults living with HIV and to identify predictors of virological failure (VF).MethodsBetween November 2014 and January 2016, a prospective, population-based cohort study was conducted among HIV-positive adults under first-line treatment and monitored at the Accredited HIV Care Center (AHCC) of Laquintinie Hospital of Douala. Clinical and biological data at the initiation of ART were collected from patients’ medical records. HIV VL at 12 and 24 months after the patient started treatment on ART were performed using quantitative real-time PCR protocol with the generic HIV Roche TaqMan assay. Descriptive and logistic regression analysis were performed in Stata SE11 version in data analysis.ResultsOverall 150 (45.5%) of 330 adults living with HIV were tested with at least one VL, and of these patients, 51 (34.0%) were tested with two VL during the followed-up. The VF was observed in 13 of 51 (25.5%) patients and among them, 8 (61.5%) switched to second-line ART regimens. Thirty-five (68.6%) of the 51 patients had an undetectable VL at the first VL measurement, and seven (13.7%) patients subsequently developed viral load rebound (VLR) on tritherapy. Using a multivariate analysis, the risk of VF was seven times higher in HIV adults who did not respect the medication hours (OR = 7.38, 95%CI = 1.56–34.90, p = 0.012) and eleven times higher in patients with none or primary school education (OR = 11.38, 95% CI = 2.41–53.76, p = 0.002).ConclusionLow education level and poor adherence are the main risk factors for VF. Strengthening therapeutic failure prevention strategies and routine VL surveillance would allow early detection of VF and contribute in achieving the third goal of UNAIDS which recommends “90–90-90” targets for People Living with HIV in resource-limited settings.

Adoption of routine virologic testing and predictors of virologic failure among HIV-infected children on antiretroviral treatment in western Kenya.

BackgroundAccess to routine virologic monitoring, critical to ensuring treatment success, remains limited in low- and middle-income countries. We report on implementation of routine viral load (VL) monitoring and risk factors for virologic failure among HIV-infected children on antiretroviral treatment (ART) in Western Kenya.MethodsRoutine VL testing was introduced in western Kenya in November 2013. We performed a case-control study among 1190 HIV-infected children ≤15 years on ART who underwent routine VL testing June 2014–May 2015. A random sample of 98 cases (virologic failure define as VL >1000 cps/mL) and 201 controls (VL <1000 cps/mL) from five facilities in three high HIV prevalence counties in Kenya were followed for a minimum of 12 months. Data from patient charts were analyzed using logistic regression to determine factors associated with failure to attain virologic suppression at initial routine and subsequent VL testing among cases.ResultsOverall, 1190 (94%) children with a median age of 8 years underwent routine VL testing of whom (37%) had virological failure. Among the 299 cases and controls, WHO stage, baseline CD4 count and time since ART initiation were not associated with virologic failure during the follow-up period. In multivariable analysis, unsuppressed children at initial test were more likely to be male (adjusted Odds Ratio (aOR) 2.1, 95% Confidence Interval (CI) 2.1–3.6) and have had an ART regimen change (aOR 2.0, CI 1.0–3.7) than controls. Of the two-thirds of children 201/299 who had a subsequent VL performed, VL suppression was greater among those suppressed at initial test 126/135 (93.3%) compared to children with virologic failure 15/66 (22.7%, p<0.0001). Among those failing at first test who achieved viral suppression in follow up, 12/15 (80%) were on a protease inhibitor (PI)-based regimen. In the multivariable analysis of children with subsequent VL testing, children on PI-based 2nd line regimens were 10-fold more likely to achieve viral suppression than children on first-line NNRTI-based ART (adjusted Odds Ratio [aOR] 0.1; 95%CI 0.0–0.4).ConclusionCoverage of initial routine viral load testing among children on ART in western Kenya is high. However, subsequent testing and virologic suppression are low in children with virologic failure on initial routine viral load test. There is an urgent need to improve management and viral load monitoring of children living with HIV experiencing treatment failure to ensure improved long-term outcomes.

Virological failure among adolescents on ART, Harare City, 2017- a case-control study

BackgroundZimbabwe is on track towards achieving viral suppression among adults (87%). However, adolescents have only achieved 44% by 2016. In Harare city, 57% of adolescents had attained viral suppression after 12 months on ART compared to 88% among adults. We determined factors associated with virological failure among adolescents (age 10–19 years) on antiretroviral therapy (ART) in Harare city.MethodsWe conducted a one to one unmatched case control study among 102 randomly recruited case: control pairs at the two main infectious disease hospitals in Harare. A case was any adolescent who presented with VL > 1000c/ml after at least 12 months on ART. A control was any adolescent who presented with VL < 1000c/ml after at least 12 months on ART. Interviewer administered questionnaires were used to collect data. Epi Info 7 was used to generate frequencies, means, proportions, ORs and p-values at 95% CI.ResultsWe interviewed 102 case-control pairs. Poor adherence to ART [aOR = 8.15, 95% CI (2.80–11.70)], taking alcohol [aOR = 8.46, 95% CI (3.22–22.22)] and non- disclosure of HIV status [aOR = 4.56, 95% CI (2.20–9.46)] were independent risk factors for virological failure. Always using a condom [aOR = 0.04, 95% CI (0.01–0.35)], being on second line treatment [aOR = 0.04, 95% CI (0.23–0.81)] and belonging to a support group [aOR = 0.41, 95% CI (0.21–0.80)] were protective.ConclusionPoor adherence, alcohol consumption and non-disclosure increased the odds of virological failure. Based on these findings support should focus on behavior change and strengthening of peer to peer projects to help address issues related to disclosure and adherence. Further operational research should aim to define other components of effective adherence support for adolescents with virological failure.

Religious Beliefs and Depression: Psychosocial Factors Affecting HIV Treatment Outcomes in South Africa

Analyzing factors associated with virological failure (VF) may improve antiretroviral therapy (ART) outcomes for individuals living with HIV. The Risk Factors for Virological Failure (RFVF) study compared 158 cases with VF (viral load, VL, >1,000 copies/mL) and 300 controls with virological suppression (VL ≤1,000 copies/mL) after ≥5 months on their first ART regimen at McCord Hospital in Durban, South Africa between October 2010 and June 2012. RFVF participants completed a battery of various psychosocial measures. Using multivariate logistic regression stratified for gender, the association of various psychosocial factors with VF was assessed. It was found that not all factors were equally significant for both genders. The factors that were significantly associated with VF for both genders were younger age, shorter treatment duration and reporting depressive symptoms. The factors associated with VF that differed by gender were religious inactivity, having HIV+ family members, and status disclosure to friends.

Virological Outcomes of Second-line Protease Inhibitor-Based Treatment for Human Immunodeficiency Virus Type 1 in a High-Prevalence Rural South African Setting: A Competing-Risks Prospective Cohort Analysis.

Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001). Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed. NCT01509508.

Multicentre analysis of second-line antiretroviral treatment in HIV-infected children: adolescents at high risk of failure.

Introduction: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART. Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment. Results: We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person-years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions: In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.

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.