Virological failure and adherence to antiretroviral therapy in adolescents and young adults living with human immunodeficiency virus

Objective

HIV (human immunodeficiency virus) infection remains a major public health challenge. Infected young people at any age are less likely to adhere to care in a timely manner and to maintain a suppressed VL. This review aims to identify factors associated with virologic failure and adherence to drug therapy in adolescents and young adults (10–24 years) living with HIV.

Methods

Systematic review using the PubMed and Virtual Health Library databases and including articles published between 2009 and 2021. Data were analysed in six categories: individual factors, pharmacological/therapy-related aspects, factors related to HIV/acquired immunodeficiency syndrome (AIDS) infection, HIV/AIDS stigma, social support and health system/services. The study's protocol was registered on the PROSPERO platform (CRD42020167581).

Results

A total of 19,819 articles were found in the initial search and 31 studies were included in this systematic review. Most studies were carried out on the African continent. Male sex, alcohol use, low education, adverse effects of medication, lack of social support, stigma related to HIV/AIDS, need for transportation to access the health service and forgetfulness were linked to poor adherence to therapy. Good adherence was achieved with sufficient nutrition, good social support, greater confidence in the use of therapy and fewer ART side effects. Low levels of CD4, alcohol use, substance abuse, low education, non-adherence to medication and forgetfulness were linked to virological failure.

Conclusion

Individual, social and structural factors constitute barriers to adherence to ART among adolescent and young adults. It is necessary to know the difficulties related to the use of therapy to work out specific strategies that create conditions to improve medication adherence and viral suppression, reducing the levels of virological failure in this population.     

Keeping kids in care: virological failure in a paediatric antiretroviral clinic and suggestions for improving treatment outcomes

The burden of paediatric HIV in South Africa is extremely high. Antiretrovirals (ARVs) are now widely accessible in the country and the clinical emphasis has shifted from initiation of treatment to retention in care. This study describes the cumulative virological failure rate amongst children on ARVs in a peri-urban clinic, and suggests ways in which clinics and partners could improve treatment outcomes. The study was conducted by the non-profit organisation HOPE Cape Town Association. A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all children with a viral load >1000 copies/ml, children on monotherapy, children who had stopped treatment, children lost to follow-up (LTFU) and children who had died. Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care. Cumulative virological failure rate was 42%, with most of those children having been LTFU. Both staff and caregivers consistently identified pharmacy queues, ongoing stigma and unpalatable ARVs as barriers to adherence. Staff suggestions included use of adherence aids, and better education and support groups for caregivers. Caregivers also requested support groups, as well as “same day” appointments for caregivers and children, but rejected the idea of home visits. Simple, acceptable and cost-effective strategies exist whereby clinics and their partners could significantly reduce the cumulative virological failure rate in paediatric ARV clinics. These include actively tracing defaulters, improving education, providing support groups, and campaigning for palatable ARV formulations.     

Improved long-term antiretroviral treatment outcomes amongst patients receiving community-based adherence support in South Africa

Retaining high levels of patients in care who are virally suppressed over long treatment periods has been an important challenge for antiretroviral treatment (ART) programmes in sub-Saharan Africa, the region having the highest HIV burden globally. Clinic-linked community-based adherence support (CBAS) programmes provide home-based adherence and psychosocial support for ART patients. However, there is little evidence of their longer-term impact. This study assessed the effectiveness of CBAS after eight years of ART. CBAS workers are lay healthcare personnel providing regular adherence and psychosocial support for ART patients and their households through home visits addressing household challenges affecting adherence. A multicentre cohort study using routinely collected data was undertaken at six public ART sites in a high HIV-prevalence South African district. Patient retention, loss to follow-up (LTFU), viral suppression and CD4 cell restoration were compared between patients with and without CBAS, using competing-risks regression, linear mixed models and log-binomial regression. 3861 patients were included, of whom 1616 (41.9%) received CBAS. Over 14,792 patient-years of observation, the cumulative incidence of LTFU was 37.3% and 46.2% amongst patients with and without CBAS, respectively, following 8 years of ART; adjusted subhazard ratio (CBAS vs. no CBAS)?=?0.74 (95% CI: 0.66–0.84; P?P?=?.015). Annual CD4 cell increases from baseline were 62.8 cells/µL/year and 51.5 cells/µL/year amongst patients with and without CBAS, respectively, after 6.5 years or more (P?=?.034). After adjustment, annual CD4 cell recovery was 15.1 cells/µL/year (95% CI: 2.7–27.6) greater in CBAS patients (P?=?.017). ART patients who received CBAS had improved long-term patient retention, viral suppression and immunological restoration. CBAS is an intervention that can improve longer-term ART programme outcomes in resource-limited settings.     

Predictive factors for immunological and virological endpoints in Thai patients receiving combination antiretroviral treatment

BACKGROUND: Routine CD4 count and HIV viral load monitoring is a financial barrier in developing countries. METHODS: We assessed factors associated with CD4 counts < or =200 cells/microL and detectable viral load in Thai HIV-infected patients receiving antiretroviral therapy (ART) at the HIV Netherlands Australia Thailand Research Collaboration and the Thai Red Cross AIDS Research Centre (HIV-NAT). Univariate and multivariate Cox proportional hazards models for multiple treatment failures were used to determine factors related to CD4 counts < or =200 cells/microL and detectable viral load. Multivariate Cox proportional hazards models for CD4 counts < or =200 cells/microL were developed with and without viral load in order to build models applicable to contexts in which viral load is not available. RESULTS: Four hundred and seventeen patients were included in the study. Fifty-four per cent were male, and the median CD4 count and log(10) viral load at baseline were 283 cells/microL and 4.3 log(10) HIV-1 RNA copies/mL, respectively. Independent factors related to CD4 count < or =200 cells/microL were CD4 count at baseline [hazards ratio (HR) 0.20/100 cells/microL; 95% confidence interval (CI) 0.17-0.23] and changes in CD4 count (HR 0.22/100 cells/microL; 95% CI 0.17-0.28). Factors in multivariate models (in which viral load was considered for inclusion) were CD4 count at baseline (HR 0.21/100 cells/microL; 95% CI 0.18-0.24), changes in CD4 count (HR 0.25/100 cells/microL; 95% CI 0.19-0.32) and detectable viral load (HR 1.94; 95% CI 1.20-3.13). Predictive factors (independent of viral load) were triple ART or highly active antiretroviral therapy (HAART) (HR 0.28; 95% CI 0.22-0.36) and detectable viral load at baseline (HR 2.96; 95% CI 2.24-3.91). Conclusions CD4 count at baseline and changes in CD4 count were important in predicting CD4 counts < or =200 cells/microL. Triple ART and detectable viral load at baseline were important in predicting detectable viral load.     

心脏再同步化治疗在严重心力衰竭中的应用

心力衰竭是各种心脏病的终末阶段,用心脏再同步化(CRT)的技术治疗中重度心力衰竭患者是一个新的治疗方法。CRT又名心房同步双心室起搏装置,近年来一系列短期和长期的临床试验已报道了这项治疗的临床效益,认为是严重心力衰竭合并心电学异常患者的一种理想的非药物辅助治疗选择。文章综述了心脏再同步化治疗的机制,相关的临床试验,临床思考和存在的技术问题,同时强调该方法目前还处于探索研究阶段,但已显示其光明的前景。     

Tuberculosis incidence among people living with HIV/AIDS with virological failure of antiretroviral therapy in Salvador,Bahia, Brazil

Antiretroviral therapy for HIV has led to increased survival of HIV-infected patients. However, tuberculosis remains the leading opportunistic infection and cause of death among people living with HIV/AIDS. Tuberculosis has been shown to be a good predictor of virological failure in this group. This study aimed to evaluate the incidence of tuberculosis and its consequences among individuals diagnosed with virological failure of HIV. This was a retrospective cohort study involving people living with HIV/AIDS being followed-up in an AIDS reference center in Salvador, Bahia, Brazil. Individuals older than 18 years with HIV infection on antiretroviral therapy for at least six months, diagnosed with virological failure (HIV-RNA greater than or equal to 1000 copies/mL), from January to December 2013 were included. Tuberculosis was diagnosed according to the criteria of the Brazilian Society of Pneumology. Fourteen out of 165 (8.5%) patients developed tuberculosis within two years of follow-up (incidence density = 4.1 patient-years). Death was directly related to tuberculosis in 6/14 (42.9%). A high incidence and tuberculosis-related mortality was observed among patients with virological failure. Diagnosis of and prophylaxis for tuberculosis in high-incidence countries such as Brazil is critical to decrease morbidity and mortality in people living with HIV/AIDS.     

Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD)

Objective The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD).
Methods Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria.
Results Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person-years (7.8 per 100 person-years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person-years). There was no difference between patients from high- and low-income countries [adjusted hazard ratio (HR) 1.02; P =0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs . A; adjusted HR 1.38, P =0.040], a lower CD4 count (≥51 cells/μL vs . ≤50 cells/μL; adjusted HR 0.61, P =0.022) and a higher HIV viral load (≥400 HIV-1 RNA copies/mL vs . <400 copies/mL; adjusted HR 2.69, P <0.001) were associated with a higher rate of treatment modification after failure. Compared with patients from low-income countries, patients from high-income countries were more likely to change two or more drugs (67% vs . 49%; P =0.009) and to change to a protease-inhibitor-containing regimen (48% vs . 16%; P <0.001).
Conclusions In a cohort of Asian patients with HIV infection, nearly half remained on the failing regimen in the first year following documented treatment failure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second-line treatment. There is a need to scale up the availability of second-line regimens and virological monitoring in this region.     

12例急性期HIV感染者抗病毒治疗结果分析

目的初步探讨急性期艾滋病病毒(HIV)感染者进行抗病毒治疗(ART)对其预后的影响。方法对在佑安医院接受抗病毒治疗的12例急性期HIV感染者进行跟踪随访和分析。结果 12例HIV感染者均在感染6个月内开始ARV治疗,并坚持服药未中断治疗,随访治疗期6个月-3年。治疗后3个月内检测病毒载量均低于最低检测限,1年后CD4+T细胞数均>500/μL,无明显严重药物不良反应发生,HIV感染者生存状态良好。结论初步结果显示,急性期开始抗病毒治疗可能为艾滋病病人带来好的预后结果。     

社区获得性肺炎初始治疗失败原因分析

社区获得性肺炎(CAP)是一种常见病,其全球发病率为2～12例/(1000人˙年)。美国每年发生500万～1000万例,其中110万次需住院治疗,死亡45 000例。不需要住院治疗者病死率在1%以下,需要住院治疗者病死率为12%～14%,而入住重症监护病房(ICU)、发生菌血症者比例则高达     

Extended antiretroviral treatment interruption in HIV-infected patients with long-term suppression of plasma HIV RNA

OBJECTIVES: Evaluation of extended treatment interruption (TI) in chronic HIV infection among patients successfully treated with antiretroviral therapy. METHODS: An observational analysis of 25 patients in a prospectively followed cohort with chronic HIV infection, viral loads <500 HIV-1 RNA copies/mL for at least 6 months, and an interruption in therapy of >/=28 days duration was carried out. Follow up was divided into 3-month time periods for analysis. The effects of time period, stratification group and stratification group by time period interactions on CD4 counts were tested using a mixed model. Univariate comparisons among patient characteristics and responses were performed using Fisher's exact test or the Wilcoxon rank sum test. RESULTS: At initiation of TI, the median CD4 count was 799 cells/microL. TI duration was a median of 7.1 months. HIV RNA rebounded to a median maximum level of 75 000 copies/mL. Maximum viral rebound was significantly greater in patients who were male, had lipodystrophy and had zenith HIV RNA prior to TI of >/=50 000 copies/mL. Lower CD4 cell counts were observed during TI in patients with lipodystrophy, zenith HIV RNA >/=50 000 copies/mL, history of AIDS, HIV infection >/=5 years and presuppression CD4 count 相似文献   

Persistent low-level viraemia and virological failure in HIV-1-infected patients treated with highly active antiretroviral therapy

OBJECTIVE: To assess the prognostic significance of persistent low-level viraemia (PLV, defined as persistent plasma viral loads of 51-1000 HIV-1 RNA copies/mL for at least 3 months) in patients who had achieved viral suppression on antiretroviral therapy (ART). METHODS: A retrospective cohort of HIV-infected patients who received ART, were followed-up for > or =12 months, made regular visits to the clinic during which blood tests were performed for an ultrasensitive HIV RNA assay every 3 months, and achieved viral loads <50 copies/mL were evaluated. Virological failure was defined as two consecutive viral load measurements >1000 copies/mL. RESULTS: Of 362 patients, 78 (27.5%) experienced PLV. The demographics of patients with and without PLV were similar. PLV occurred at a mean (+/-standard deviation) of 22.6+/-16.9 months after ART initiation and lasted for 6.4+/-3.4 months. During a median follow-up of 29.5 months, patients with PLV had a higher rate of virological failure (39.7% vs 9.2%; P < 0.001). The median time to failure was 68.4 months [95% confidence interval (CI) 37.0-99.7] for patients with PLV and >72 months for patients without PLV (log rank test, P < 0.001). By Cox regression, patients with PLV had a greater risk of virological failure [hazard ratio (HR) 3.8; 95% CI 2.2-6.4; P < 0.001]. Among patients with PLV, a PLV of >400 copies/mL (HR 3.3; 95% CI 1.5-7.1; P = 0.003) and a history of ART (HR 2.4; 95% CI 1.0-5.7; P = 0.042) predicted virological failure. CONCLUSIONS: PLV is associated with virological failure. Patients with a PLV >400 copies/mL and a history of ART experience are more likely to experience virological failure. Patients with PLV should be considered for treatment optimization and interventional studies.     

Sex differentials in the uptake of antiretroviral treatment in Zambia

This study explores socio-structural factors that influence uptake of antiretroviral treatment (ART) in Zambia and assess differences between men and women. We conducted a case-control study nested in a community- and health facility-based survey, between September 2010 and February 2011. Cases were defined as HIV-positive individuals who, while eligible, never started ART and controls were HIV-positive individuals who were on ART. Cases and controls were matched by place of residence. We performed a conditional logistic regression analysis using a discrete logistic model stratified by sex. Overall, a significantly larger proportion of men (32.7%) than women (25.6%) did not uptake ART (Pearson χ² = 5.9135; p = 0.015). In the crude analysis, poor health status and low self-efficacy were common factors associated with non-uptake in both sexes. After adjusting for covariates, men were more likely than women to refuse ART even though men's self-rated health was lower than women's. In general, the adjusted analysis suggests that HIV status disclosure affects uptake in both sexes but women's uptake of ART is largely hampered by poverty-related factors while for men, side effects and social pressure, probably associated with masculinity, are more important barriers. Alarmingly men's health seems to deteriorate until they start treatment, in contrast to women. Understanding gender differences in uptake and attitudes to ART is a crucial component to providing effective and appropriate health care to both men and women living with HIV/AIDS in Zambia.     

Long-term quality of life outcomes in three antiretroviral treatment strategies for HIV-1 infection

OBJECTIVE: To compare changes in quality of life (QoL) over 96 weeks in patients enrolled in a triple-therapy protocol, a treatment-intensification protocol, or an induction-maintenance therapy protocol, and to compare QoL between patients who continued and discontinued their antiretroviral regimen. PATIENTS: Naive patients enrolled in a triple-therapy protocol (zidovudine/lamivudine or stavudine/didanosine or stavudine/lamivudine supplemented with protease inhibitor therapy of choice) (n = 35), a protocol of treatment intensification (ritonavir/saquinavir or ritonavir/saquinavir/stavudine) (n = 74) in which therapy was intensified with nucleoside analogue(s) in cases of insufficient viral suppression, and a protocol of induction (saquinavir/nelfinavir/lamivudine/ stavudine) maintenance (saquinavir/nelfinavir or stavudine/nelfinavir) therapy (n = 50). MAIN OUTCOME MEASURE: Changes from baseline in QoL assessed by the Medical Outcomes Study HIV Health Survey at weeks 0, 12, 24, 36, 48, 72 and 96. RESULTS: Patients in the triple-therapy and treatment-intensification protocols showed more favourable changes in physical function, social function, mental health, energy/fatigue, health distress and overall QoL compared to patients in the induction-maintenance protocol, with patients in the first two protocols showing improvements in QoL and those in the induction-maintenance protocol showing declining or unchanged QoL. Patients who discontinued study medication due to insufficient efficacy, toxicities or at their own request showed less favourable changes in QoL compared with patients who continued their regimen. The highest proportion of discontinuations was within the induction-maintenance protocol. CONCLUSION: Antiretroviral treatment strategies that are effective and tolerable have the potential to improve patients' QoL over 96 weeks.