scholarly journals The impact of delayed switch to second-line antiretroviral therapy on mortality, depending on failure time definition and CD4 count at failure

2019 ◽  
Author(s):  
Helen Bell-Gorrod ◽  
Matthew P Fox ◽  
Andrew Boulle ◽  
Hans Prozesky ◽  
Robin Wood ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Failure Time ◽  
Likelihood Estimation ◽  
Cd4 Count ◽  
Second Line ◽  
Switch Time ◽  
Measured Time ◽  
Treatment Switch ◽  
Relationship Of ◽  
The Impact

ABSTRACTBackgroundLittle is known about the functional relationship of delaying second-line treatment initiation for HIV-positive patients and mortality, given a patient’s immune status.MethodsWe included 7255 patients starting antiretroviral therapy between 2004-2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting (IPTW) of marginal structural models. The non-linear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation (TMLE). We adjusted for measured time-varying confounding by CD4 count, viral load and visit frequency.Results5-year mortality was estimated as 10.5% (2.2%; 18.8%) for immediate switch and as 26.6% (20.9%; 32.3%) for no switch (49.9% if CD4 count<100 cells/mm3). The hazard of death was estimated to be 0.40 (95%CI: 0.33-0.48) times lower if everyone had been switched immediately compared to never. The shorter the delay in switching, the lower the hazard of death, e.g. delaying 30-60 days reduced the hazard 0.52 (0.41-0.65) times, and 60-120 days 0.56 (0.47-0.66) times.ConclusionsEarly treatment switch is particularly important for patients with low CD4 counts at failure.

scholarly journals The Impact of Delayed Switch to Second-Line Antiretroviral Therapy on Mortality, Depending on Definition of Failure Time and CD4 Count at Failure

2020 ◽  
Vol 189 (8) ◽  
pp. 811-819 ◽  
Author(s):  
Helen Bell-Gorrod ◽  
Matthew P Fox ◽  
Andrew Boulle ◽  
Hans Prozesky ◽  
Robin Wood ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Failure Time ◽  
Likelihood Estimation ◽  
Cd4 Count ◽  
Second Line ◽  
Switch Time ◽  
Measured Time ◽  
Definition Of ◽  
Relationship Of ◽  
The Impact

Abstract Little is known about the functional relationship of delaying second-line treatment initiation for human immunodeficiency virus–positive patients and mortality, given a patient’s immune status. We included 7,255 patients starting antiretroviral therapy during 2004–2017, from 9 South African cohorts, with virological failure and complete baseline data. We estimated the impact of switch time on the hazard of death using inverse probability of treatment weighting of marginal structural models. The nonlinear relationship between month of switch and the 5-year survival probability, stratified by CD4 count at failure, was estimated with targeted maximum likelihood estimation. We adjusted for measured time-varying confounding by CD4 count, viral load, and visit frequency. Five-year mortality was estimated to be 10.5% (95% CI: 2.2, 18.8) for immediate switch and to be 26.6% (95% CI: 20.9, 32.3) for no switch (51.1% if CD4 count was &lt;100 cells/mm3). The hazard of death was estimated to be 0.37 (95% CI: 0.30, 0.46) times lower if everyone had been switched immediately compared with never. The shorter the delay in switching, the lower the hazard of death—delaying 30–59 days reduced the hazard by 0.53 (95% CI: 0.43, 0.65) times and 60–119 days by 0.58 (95% CI: 0.49, 0.69) times, compared with no switch. Early treatment switch is particularly important for patients with low CD4 counts at failure.

scholarly journals Estimating the Impact and Cost of the WHO 2010 Recommendations for Antiretroviral Therapy

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
John Stover ◽  
Lori Bollinger ◽  
Carlos Avila
Keyword(s):  
Antiretroviral Therapy ◽  
Cd4 Count ◽  
Eligibility Criterion ◽  
Eligibility Criteria ◽  
Art Programs ◽  
Middle Income ◽  
Middle Income Countries ◽  
Country Level ◽  
Potential Impact ◽  
The Impact

In July 2010, WHO published new recommendations on providing antiretroviral therapy to adults and adolescents, including starting ART earlier, usually at a CD4 count of 350 or lower, specific regimens for first- and second-line therapies, and other recommendations. This paper estimates the potential impact and cost of the revised guidelines by first, calculating the number of people that would be in need of antiretroviral therapy (ART) with different eligibility criteria, and second, calculating the costs associated with the potential impact. Results indicate that switching the eligibility criterion from CD4 count <200 to <350 increases the need for ART in low- and middle-income countries (country-level) by 50% (range 34% to 70%). The costs of ART programs only to increase coverage to 80% by 2015 would be 44% more (range 29% to 63%) when switching the eligibility criterion to CD4 count <350. When testing and outreach costs are included, total costs increase by 62%, from US$26.3 billion under the previous eligibility criterion of treating those with CD4 <200 to US$42.5 billion using the revised eligibility criterion of treating those with CD4 <350.

scholarly journals Epidemiology and Outcomes in Critically Ill Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Shannon L. Turvey ◽  
Sean M. Bagshaw ◽  
Dean T. Eurich ◽  
Wendy I. Sligl
Keyword(s):  
Critical Illness ◽  
Antiretroviral Therapy ◽  
Cox Regression ◽  
Illness Severity ◽  
Cd4 Count ◽  
Apache Ii Score ◽  
Predictors Of Mortality ◽  
Immunodeficiency Virus ◽  
Artery Disease ◽  
The Impact

Purpose.The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality.Materials and Methods.Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality.Results.Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male. Median (IQR) CD4 count and plasma viral load (PVL) were 125 cells/mm3(30–300) and 28,000 copies/mL (110–270,000). Fifty-five (20%) patients died within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12; 95% CI 1.08–1.16;p<0.001), cirrhosis (aHR 2.30; 95% CI 1.12–4.73;p=0.024), coronary artery disease (aHR 6.98; 95% CI 2.20–22.13;p=0.001), and duration of HIV infection (aHR 1.07 per year; 95% CI 1.02–1.13;p=0.01). CD4 count and PVL were not associated with mortality.Conclusions.Mortality from an episode of critical illness in HIV-infected patients remains high but appears to be driven by acute illness severity and HIV-unrelated comorbid disease rather than degree of immune suppression.

Effectiveness of second-line antiretroviral therapy: the impact of drug switches

AIDS Care ◽  
2017 ◽  
Vol 29 (12) ◽  
pp. 1585-1588
Author(s):  
Letícia Penna Braga ◽  
Cássia Cristina Pinto Mendicino ◽  
Edna Afonso Reis ◽  
Ricardo Andrade Carmo ◽  
Cristiane Aparecida Menezes de Pádua
Keyword(s):  
Antiretroviral Therapy ◽  
Second Line ◽  
The Impact ◽  
Second Line Antiretroviral Therapy

scholarly journals The impact of antiretroviral therapy on symptom burden among HIV outpatients with low CD4 count in rural Uganda: nested longitudinal cohort study

2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Katie Wakeham ◽  
Richard Harding ◽  
Jonathan Levin ◽  
Rosalind Parkes-Ratanshi ◽  
Anatoli Kamali ◽  
...  
Keyword(s):  
Cohort Study ◽  
Antiretroviral Therapy ◽  
Symptom Burden ◽  
Cd4 Count ◽  
Longitudinal Cohort Study ◽  
Longitudinal Cohort ◽  
The Impact

scholarly journals Aripiprazole Improves Depressive Symptoms and Immunological Response to Antiretroviral Therapy in an HIV-Infected Subject with Resistant Depression

2010 ◽  
Vol 2010 ◽  
pp. 1-4 ◽  
Author(s):  
Chiara Cecchelli ◽  
Giacomo Grassi ◽  
Stefano Pallanti
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Immunological Response ◽  
Cd4 Count ◽  
Hiv Positive ◽  
Psychotropic Agents ◽  
Resistant Depression ◽  
Present Case Study ◽  
The Impact

Aripiprazole is the first medication approved by the FDA as an add-on treatment for MDD. The impact of aripiprazole on the response to HIV is unknown. The patient we report on was diagnosed HIV-positive in 1997 and has been treated with antiretroviral therapy since then. In 2008, we diagnosed resistant major depression, hypochondria, and panic disorder. On that occasion, blood tests showed a significantly reduced CD4 count and a positive viral load. We treated this patient with aripiprazole and citalopram. Mood, somatic symptoms, and occupational functioning progressively improved. The last blood examination showed an increase in the CD4 count and a negative viral load. On the basis of the present case study and the review of the literature concerning the effects of psychotropic agents on viral replication, we suggest that the use of aripiprazole in HIV-infected subjects warrants further research.

scholarly journals Impact of HIV-1 CRF55_01B infection on the evolution of CD4 count and plasma HIV RNA load in men who have sex with men prior to antiretroviral therapy

2021 ◽  
Author(s):  
Lan Wei ◽  
Hao Li ◽  
Xing Lv ◽  
Chenli Zheng ◽  
Guilian Li ◽  
...  
Keyword(s):  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cd4 Count ◽  
Transmission Risk ◽  
Mixed Effect ◽  
Cd4 Cell Count ◽  
Hiv Rna ◽  
Subtype B ◽  
The Impact ◽  
Hiv 1

Abstract Background CRF55_01B is a newly identified HIV-1 circulating recombinant form originated from MSM in China. However, its impact on the disease progression and transmission risk has not been investigated. This study aimed to determine the impact of CRF55_01B infection on viral dynamics and immunological status, so as to provide implications for future prevention, treatment, or target interventions. Linear mixed effect models were applied to evaluate CD4 cell count decline and viral load increase by subtype.Results Of the 3418 blood samples, 1446 (42.3%) were CRF07_BC, 1169 (34.2%) CRF01_AE, 467 (13.7%) CRF55_01B, 249 (7.3%) type B, and 87 (2.5%) other subtypes (CRF_08BC, CRF_01B, C). CRF55_01B had replaced subtype B as the third predominant strain since 2012 in Shenzhen, China. CRF55_01B-infected MSM showed lower median of CD4 count than CRF07_BC-infected MSM (349.5 [IQR, 250.2~474.8] vs 370.0 [IQR, 278.0~501.0], P<0.05). CRF55_01B infection was associated with slower loss of CD4 count than CRF01_AE (13.6 vs 23.3 [cells/μL]¹/²/year, P<0.05)among MSM with initial CD4 count of 200~350 cells/μL. On the other hand, those infected with CRF55_01B showed higher median plasma HIV RNA load (5.4 [IQR, 5.0~5.9]) than both CRF01_AE (5.3 [IQR, 4.8~5.7], P<0.05) and CRF07_BC (5.0 log10 [IQR, 4.5~5.5], P<0.001) at the initiation of antiretroviral therapy. Furthermore, the annual increasing rate of viral load for CRF55_01B infection was significantly higher than that of CRF07_BC (2.0 vs 0.7 log10 copies/ml/year, P<0.01).Conclusions The relatively lower CD4 count and faster increase of plasma HIV RNA load of CRF55_01B-infected MSM without antiretroviral therapy suggest that CRF55_01B may lead to longer asymptomatic phase and higher risk of HIV transmission. Strengthened surveillance, tailored prevention strategies and interventions, and in-depth research focusing on CRF55_01B are urgently needed to forestall potential epidemic.

scholarly journals Determinants of Viral Suppression Among Adolescents on Antiretroviral Therapy in Ehlanzeni District, South Africa: A Retrospective Cohort Analysis

2021 ◽  
Author(s):  
Emeka Francis Okonji ◽  
Brian Van Wyk ◽  
Ferdinand C. Mukumbang ◽  
Gail Hughes
Keyword(s):  
South Africa ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Retrospective Cohort ◽  
Viral Suppression ◽  
Cohort Analysis ◽  
Cd4 Count ◽  
Second Line ◽  
Retrospective Cohort Analysis ◽  
Living With Hiv

Abstract Background Achieving undetectable viral loads is crucial for the reduction of HIV transmissions, AIDS related illnesses and death. Adolescents living with HIV on antiretroviral therapy (ART) have worse treatment adherence and lower viral suppression rates compared to adults. We report on the clinical factors associated with viral suppression among adolescents 10–19 years living with HIV in the Ehlanzeni district, Mpumalanga in South Africa. Methods A retrospective cohort analysis was conducted with 9,543 adolescents living with HIV, aged 10–19 years, who were enrolled in 136 ART clinics in the Ehlanzeni district. Clinical and immunological data were obtained from electronic medical records (Tier.net). Adolescents were categorized as having achieved viral suppression if their latest viral load count was < 1000 ribonucleic acid (RNA) copies/mL. Using a backward stepwise approach, a multivariate logistic regression analysis was performed to identify factors independently associated with viral suppression. Results The mean age of the participants was 14.75 years (SD = 2.8), and 55.43% were female. Mean duration on ART was 72.26 (SD = 42.3) months. Of the 9,543 adolescents with viral load results recorded, 74% had achieved viral suppression. After adjusting for other covariates, the likelihood of achieving viral suppression remained significantly higher among adolescents who were: female (AOR = 1.21, 95% CI 1.05–1.38), had CD4 count > 200 (AOR = 2.29, 95% CI 1.89–2.79), and on ART for more than 6 months (AOR = 2.75, 95% CI 1.74–4.34). Furthermore, the likelihood of having viral suppression was lower among adolescents with CD4 count < 200 at baseline (AOR = 0.76, 95% CI 0.64–0.90), and who were switched to second line regimen (AOR = 0.42, 95% CI 0.35–0.49). Conclusions Viral suppression amongst adolescents at 74% is considerably lower than the WHO target of 90%. Of particular concern for intervention is the lower rates of viral suppression amongst male adolescents. Greater emphasis should be placed to enrol adolescents on ART earlier before CD4 counts are depleted (< 200) and keeping them engaged in care (beyond 6 months). Furthermore, improved viral load monitoring may prevent unnecessary switching to second line treatment, which are costly and is a risk factor for viral non suppression.

scholarly journals Implication of First-Line Antiretroviral Therapy Choice on Second-Line Options

2017 ◽  
Vol 4 (4) ◽  
Author(s):  
Seema T Meloni ◽  
Chika K Onwuamah ◽  
Oche Agbaji ◽  
Beth Chaplin ◽  
David O Olaleye ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Second Line ◽  
Resistance Mutations ◽  
First Line ◽  
Paired Samples ◽  
Therapy Choice ◽  
Significant Difference ◽  
The Impact

Abstract Background Although there are a number of studies comparing the currently recommended preferred and alternative first-line (1L) antiretroviral therapy (ART) regimens on clinical outcomes, there are limited data examining the impact of 1L regimen choice and duration of virologic failure (VF) on accumulation of drug resistance mutations (DRM). The patterns of DRM from patients failing zidovudine (AZT)-containing versus tenofovir (TDF)-containing ART were assessed to evaluate the predicted susceptibility to second-line (2L) nucleoside reverse-transcriptase inhibitor (NRTI) backbone options in the context of an ongoing programmatic setting that uses viral load (VL) monitoring. Methods Paired samples from Nigerian ART patients who experienced VF and switched to 2L ART were retrospectively identified. For each sample, the human immunodeficiency virus (HIV)-1 polymerase gene was sequenced at 2 time points, and DRM was analyzed using Stanford University’s HIVdb program. Results Sequences were generated for 191 patients. At time of 2L switch, 28.2% of patients on AZT-containing regimens developed resistance to TDF, whereas only 6.8% of patients on TDF-containing 1L had mutations compromising susceptibility to AZT. In a stratified evaluation, patients with 0–6 months between tested VL samples had no difference in proportion compromised to 2L, whereas those with &gt;6 months between samples had a statistically significant difference in proportion with compromised 2L NRTI. In multivariate analyses, patients on 1L AZT had 9.90 times higher odds of having a compromised 2L NRTI option than patients on 1L TDF. Conclusions In the context of constrained resources, where VL monitoring is limited, we present further evidence to support use of TDF as the preferred 1L NRTI because it allows for preservation of the recommended 2L NRTI option.

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