Antiretroviral Therapy Modification Research Articles

Human Immunodeficiency Virus (HIV) Treatment With Antiretroviral Therapy Mitigates the High Risk of Mental Health Disorders Associated With HIV Infection in the US Population.

Whether treatment of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) is associated with lower risk of mental health disorders (MHDs) among people with HIV (PWH) remains unknown. We aim to determine the association between HIV and MHDs and whether ART alters the risk of MHDs among PWH in the US adult population. We conducted a real-world study using the Merative MarketScan claims database (2016-2020), identifying individuals with HIV (diagnosed using International Classification of Diseases, Tenth Revision, Clinical Modification codes) and those without HIV. A multivariable stratified Cox proportional hazard regression model was conducted to examine the association of HIV treatment status with MHDs, adjusting for potential confounders. Additionally, we sought to determine the effect modification of ART on the relationship between living with HIV and MHDs. A total of 313 539 individuals, with a mean age of 44.2 (standard deviation, 11.4) years, predominantly males (81.2%), residing in the South region of the US (50.9%) were included in the present analysis. During 671 880 person-years of follow-up, 46 235 incident MHD cases occurred. In the multivariable Cox proportional hazard model, living with HIV was associated with higher risk of incident MHDs. Relative to those without HIV, the adjusted hazard ratio was 1.85 (95% confidence interval [CI], 1.79-1.92; P < .001) for those with HIV on treatment, and 2.70 (95% CI, 2.59-2.82; P < .001) for those with HIV without any treatment. Stronger associations between HIV and MHDs were observed in men relative to women, among those aged 18-34 years relative to those aged 55-63 years, and among those with no overweight/obesity relative to obese individuals (Pinteraction < .001 for all). HIV was associated with an increased risk of developing MHDs. However, HIV treatment mitigated the risk.

Low-level HIV viraemia during antiretroviral therapy: Longitudinal patterns and predictors of viral suppression.

Our objective was to characterize longitudinal patterns of viraemia and factors associated with viral suppression in people with HIV and low-level viraemia (LLV) during antiretroviral therapy (ART). We included people with HIV in the EuResist Integrated Database with LLV following ART initiation after 2005. LLV was defined as two or more consecutive viral load (VL) measurements of 51-199 copies/mL 30-365 days apart after >12 months of ART. Viraemia patterns were analyzed over 24 months. Factors associated with viral suppression at 12 months after LLV episodes were identified using univariable and multivariable logistic regression. Of 25 113 people with HIV, 2474 (9.9%) had LLV. Among 1387 participants with 24 months of follow-up after LLV, 406 (29%) had persistent suppression, 669 (48%) had transient viraemic episodes, 29 (2%) had persistent LLV, and 283 (20%) had virological failure. Following LLV episodes, the proportion with detectable viraemia declined (p for trend <0.001 and 0.034, in the first and second year, respectively). At 12 months, 68% had undetectable VL, which was associated with suppression before LLV (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.2-2.4) and ART modification after LLV (aOR 1.6; 95% CI 1.0-2.4). The following factors were negatively associated with undetectable VL at 12 months: higher VL during LLV (aOR 0.57 per log10 copies/mL; 95% CI 0.37-0.89), injecting drug use (aOR 0.67; 95% CI 0.47-0.96), and regimens with protease inhibitors (aOR 0.65; 95% CI 0.49-0.87) or combined anchor drugs (aOR 0.52; 95% CI 0.32-0.85). Most people with LLV did not experience sustained viral suppression during 24-month follow-up, supporting the association between LLV and inferior treatment outcome.

Revisiting efavirenz in the era of dolutegravir: Low-dose efavirenz, a viable alternative capable of holding its own against dolutegravir-based regimens

ABSTRACT Background: First-line dual NRTI + NNRTI-based ART has shown good virological effectiveness; however, toxicity is common and is often the most common reason for modification of first-line ART. Aims: The purpose of this study is to revisit low-dose efavirenz (EFV) in the era of dolutegravir (DTG) by investigating anti-retroviral therapy (ART) switch strategies for outcomes of virological effectiveness and safety in virologically suppressed Indian persons living with HIV (PLH) on first-line dual nucleoside reverse transcriptase inhibitors (NRTI) + non-NRTI (NNRTI)-based ART. Methods: A phase-IV comparative study of consecutive cases who switched their first-line NNRTI-based ART to either EFV-400 or DTG with a dual NRTI backbone between October 2020 to December 2021 and underwent at least 48 weeks of follow-up. The study is a non-randomised trial, wherein ART regimens were based on physician choice, patient preference and drug availability. Results: A total of 102 [DTG arm: 52; EFV-400 arm: 50; intention-to-treat (ITT) population] participants met the inclusion criteria. At 48-week follow-up, virological failure was not observed in either arm. Virological suppression to &lt; 200 cp/mL was attained in 97.9% (n = 48/49; 95% confidence interval [CI]: 89.1–99.9) and 95.9% (n = 47/49; 95% CI: 86.02–99.5) of patients, respectively, in the DTG and-EFV-400 arm (ITT-populations). There was no significant difference in mean change from baseline in body weight and body mass index between DTG and-EFV-400 arms. The proportion of patients who gained ≥ 10% of their baseline body weight at 24 weeks of exposure to DTG was 16% (n = 8, 95% CI: 5.8 to 26.2) and that to EFV-400 was 10% (n = 5, 95% CI: 1.7 to 18.3) with a difference in proportions: 6.0% (95% CI: −7.1–19.1)]. There was a significant decrease at 24 weeks in mean fasting levels of lipid fractions in the DTG arm as compared to EFV-400 [total cholesterol: − 24.3 mg/dL, 95% CI: −35.2 to − 13.3 vs. −6.9 mg/dL, 95% CI: −17.9–4.1 (P = 0.029) and triglycerides:−35.9 mg/dL, 95% CI: −60.9 to − 10.9 vs. 8.6 mg/dL, 95% CI: −16.6 to 33.8 (P = 0.014)]. Adverse events (AEs) of any grade including laboratory derangements to DTG were experienced by 6% (n = 3, 95% CI: −0.6 to 12.6) and that to EFV-400 by 8% (n = 4, 95% CI: 0.5 to 15.5) with a difference in proportions: 2.0% (95% CI: −7.9 to 11.9). Grades 3–4-AE occurred in two patients, both in the EFV-400 arm. Central nervous system AEs were not observed in the DTG arm and occurred in two patients in the EFV-400 arm. Two patients in the EFV-400 arm discontinued the regimen due to AEs. Conclusion: Both DTG and EFV-400-based first-line ART show good virological effectiveness and safety profiles in patients who are virologically suppressed on dual NRTI + NNRTI-based first-line ART.

Extinguish the Fire: Anti-inflammatory Strategies for Over Immune Activation in Chronic HIV-1 Infection

Extinguish the Fire: Anti-inflammatory Strategies for Over Immune Activation in Chronic HIV-1 Infection

Predictive factors of viral load high-risk events for virological failure in HIV/AIDS patients receiving long-term antiviral therapy

BackgroundIn the era of anti-retroviral therapy (ART), the plasma HIV viral load (VL) is an important primary indicator for monitoring the HIV treatment response. To optimize the clinical management of HIV/AIDS patients, we investigated VL high-risk events related to virological failure (VF) and further explored the preventive factors of VL high-risk events.MethodsThe data were derived from China’s HIV/AIDS Comprehensive Response Information Management System. HIV infected patients who initiated or received ART in Guangxi between 2003 and 2019 were included. The contributions of VL after 6 months of ART to VF and AIDS-related death were analysed by Kaplan-Meier curves, log-rank tests and Cox regression analyses. Both descriptive analyses and bivariate logistic regression were employed to further explore the preventive factors related to VL high-risk events of VF.ResultsThe cumulative rates of VF in the high low-level viremia group (high LLV) (χ2 = 18.45; P < 0.001) and non-suppressed group (χ2 = 82.99; P < 0.001) were significantly higher than those in the viral suppression (VS) group. Therefore, the VL high-risk events of VF was defined as highest VL > 200 copies/ml after 6 months of ART. Compared with the VS group, the adjusted hazard risk was 7.221 (95% CI: 2.668; 19.547) in the high LLV group and 8.351 (95% CI: 4.253; 16.398) in the non-suppressed group. Compared with single patients, married or cohabiting (AOR = 0.591; 95% CI: 0.408, 0.856) and divorced or separated (AOR = 0.425, 95% CI: 0.207, 0.873) patients were negatively associated with VL high-risk events. So were patients acquired HIV homosexually (AOR = 0.572; 95% CI: 0.335, 0.978). However, patients who had ART modification were 1.728 times (95% CI: 1.093, 2.732) more likely to have VL high-risk events, and patients who used cotrimoxazole during ART were 1.843 times (95% CI: 1.271, 2.672) more likely to have VL high-risk events.ConclusionsA VL greater than 200 copies/ml is a VL high-risk event for VF. Intervention measurements should be adopted to optimize the surveillance of ART in patients who are single or widowed, who have ART modification, and who use cotrimoxazole during ART.

New Insights on Long-Term Hepatitis B Virus Responses in HIV-Hepatitis B virus Co-infected Patients: Implications for Antiretroviral Management in Hepatitis B virus-Endemic Settings.

WHO treatment guidelines recommend tenofovir plus lamivudine or emtricitabine as the nucleoside reverse transcriptase inhibitor backbone in first-line regimens for HIV-infected adults. Lamivudine alone is not recommended, because of the risk of hepatitis B virus (HBV) resistance. We studied HBV responses in a large cohort of co-infected patients in a resource-limited setting. Clinical centers in Uganda and Zimbabwe. DART was a randomized trial of monitoring practices in HIV-infected adults starting antiretroviral therapy. Baseline samples were tested retrospectively for HBV serological markers and HBV DNA. Longitudinal HBV DNA testing at 48 weeks and the last available sample before HBV-relevant modification of antiretroviral therapy was performed on patients with detectable HBV DNA at baseline. Two hundred twenty-four hepatitis B surface antigen-positive patients were followed for up to 4.8 years. Of the drugs with anti-HBV activity, 166 were prescribed lamivudine-tenofovir and 58 lamivudine alone. Ninety-eight percent (96/98) patients with baseline HBV DNA <6 log10 IU/mL achieved viral suppression at 48 weeks (HBV DNA <48 IU/mL), regardless of regimen, compared with 50%(26/52) for HBV DNA >6 log10 IU/mL. Of the 83 patients suppressed at 48 weeks and with follow-up data, only 7(8%) experienced viral rebound (range 200-3460 IU/mL). Of the 20 patients not suppressed at 48 weeks and with follow-up data, HBV DNA levels generally declined with lamivudine-tenofovir, but increased with lamivudine alone. Alanine transaminase flares were not observed in any patient who experienced viral rebound. The suppressive effect of lamivudine alone was highly durable (up to 5 years) in HIV-HBV co-infected patients with baseline HBV DNA <6 log10 IU/mL. It may be feasible to develop stratified approaches using lamivudine as the only drug with anti-HBV activity.

Evaluation of a Combined HIV and Geriatrics Clinic for Older People Living with HIV: The Silver Clinic in Brighton, UK.

As life expectancy in people living with HIV (PLWH) has increased, the focus of management has shifted to preventing and treating chronic illnesses, but few services exist for the assessment and management of these individuals. Here, we provide an initial description of a geriatric service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients seen in the clinic between 2016 and 2019. We present patient demographic data, assessment outcomes, diagnoses given, and interventions delivered to those seen in the clinic. The average age of attendees was 67. Primary reasons for referral to the clinic included management of complex comorbidities, polypharmacy, and suspected geriatric syndrome (falls, frailty, poor mobility, or cognitive decline). The median (range) number of comorbidities and comedications (non-antiretrovirals) was 7 (2–19) and 9 (1–15), respectively. All attendees had an undetectable viral load. Geriatric syndromes were observed in 26 (50%) patients reviewed in the clinic, with frailty and mental health disease being the most common syndromes. Interventions offered to patients included combination antiretroviral therapy modification, further health investigations, signposting to rehabilitation or social care services, and in-clinic advice. High levels of acceptability among patients and healthcare professionals were reported. The evaluation suggests that specialist geriatric HIV services might play a role in the management of older people with HIV with geriatric syndromes.

Low-Level Viremia Predicts Virological Failure in HIV-Infected Omani Patients Receiving Antiretroviral Therapy.

Background:The implication and clinical significance of low-level viremia (LLV) in HIV patients are still not clear. This study aimed to characterize the clinical outcomes and to evaluate whether LLV could predict future virological failure in a well-defined cohort of HIV-infected Omani patients attending a large HIV clinic.Methods:Patients on regular antiretroviral therapy (ART) for at least 12 months, and had at least 2 HIV RNA measurements 1 year after starting ART, were prospectively enrolled in a cohort study. LLV was defined as plasma HIV RNA between 50-200 copies/mL that persists after at least 2 consecutive measurements after 12 months of ART. Multivariate Cox proportional hazards regression model was used to measure the association among virological failure, LLV and potential predictors.Results:After 12 months of starting ART, 60 patients (40%) had undetectable viral load (UVL) < 50 copies/mL, while 37 patients (24%) had LLV and 53 patients (35%) had primary virological failure > 200 copies/mL. The incidence rates of subsequent secondary virological failure for UVL and LLV groups, were 3 and 7 cases per 1000 patient-months, respectively. Compared to UVL group, LLV group had increased risk of subsequent secondary virological failure with hazard ratio of (4.437 [95% CI, 1.26-15.55]; p = 0.02). Age, duration of HIV infection, pretreatment HIV RNA level, pretreatment CD4+ cell count, and ART adherent were associated with subsequent secondary virological failure.Conclusion:Collectively, Omani HIV patients with LLV were at a higher risk for HIV virological failure, and should be monitored closely. Further studies are need to assess whether ART modification in LLV patients would lower the risk of virological failure.

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

Brief Report: Kidney Dysfunction Does Not Contribute Significantly to Antiretroviral Therapy Modification in Treatment-Naive PLWH Receiving Initial ART.

Antiretroviral therapy (ART) durability, time to modification or cessation, has declined. The study objective was to determine whether kidney dysfunction is contributing to reduced durability. This retrospective follow-up study of CNICS evaluated treatment-naive PLWH initiating ART between 2007 and 2014. Regimen modification was defined as cessation/modification of any part of the 3-drug ART regimen. We evaluated the role of kidney dysfunction in initial regimen modification as both a mediator and effect measure modifier. Associations of the variables with the ART modification were examined using univariable and multivariable Cox proportional hazard models. Of 4515 PLWH included in the analysis, 1967 modified their ART. Of those receiving TDF-based ART (n = 3888), 1580 (41%) modified their regimen compared with 387 (62%) receiving other regimens. Overall, the median eGFR decreased by 5 mL/min/1.73 m (quartiles: first = -16, third = 0) from baseline to follow-up. Of the 128 patients with low baseline eGFR (<60 mL/min/1.73 m), the final eGFR remained low in 73% while it increased to above 60 mL/min/1.73 m in 27%. Of the 4387 with normal baseline eGFR, only 135 (3%) had a final eGFR <60 mL/min/1.73 m. Those with low eGFR at the baseline and/or final visits were more likely to modify ART than others (hazards ratio = 1.75, 95% confidence interval: 1.39 to 2.19, P < 0.001). Relative to other regimens, TDF-based ART was less likely to be modified when accounting for numerous clinical and demographic traits. For patients in our study initiated on ART, including TDF-based ART, in the last decade, kidney dysfunction is not a major factor leading to regimen modification.

Assessment and Management of HIV-Associated Cognitive Impairment: Experience from a Multidisciplinary Memory Service for People Living with HIV.

As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients seen by the clinic. We present patient demographic data, assessment outcomes, diagnoses given and interventions delivered to those seen in the clinic. 41 patients (79%) of those seen in the clinic had objective CI: 16 (31%) met criteria for HIV-associated Neurocognitive Disorder (HAND), 2 (4%) were diagnosed with dementia, 14 (27%) showed CI associated with mental illness and/or drugs/alcohol, 7 (13%) had CI which was attributed to factors other than HIV and in 2 (4%) patients the cause remains unclear. 32 (62%) patients showed some abnormality on Magnetic Resonance Imaging (MRI) brain scans. Patients attending the clinic performed significantly worse than normative scores on all tests of global cognition and executive function. Interventions offered to patients included combination antiretroviral therapy modification, signposting to other services, case management, further health investigations and in-clinic advice. Our experience suggests that the need exists for specialist HIV memory services and that such a model of working can be successfully implemented into HIV patient care. Further work is needed on referral criteria and pathways. Diagnostic processes and treatment offered needs to consider and address the multifactorial aetiology of CI in HIV and this is essential for effective assessment and management.

Virologic failure and mortality in older ART initiators in a multisite Latin American and Caribbean Cohort

IntroductionThe “greying” of the HIV epidemic necessitates a better understanding of the healthcare needs of older HIV‐positive adults. As these individuals age, it is unclear whether comorbidities and their associated therapies or the ageing process itself alter the response to antiretroviral therapy (ART). In this study, HIV treatment outcomes and corresponding risk factors were compared between older ART initiators and those who were younger using data from the Caribbean, Central and South America Network for HIV Epidemiology (CCASAnet).Methods HIV‐positive adults (≥18 years) initiating ART at nine sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Patients were classified as older (≥50 years) or younger (<50 years) based on age at ART initiation. ART effectiveness was measured using three outcomes: death, virologic failure and ART treatment modification. Cox regression models for each outcome compared risk between older and younger patients, adjusting for other covariates.ResultsAmong 26,311 patients initiating ART between 1996 and 2016, 3389 (13%) were ≥50 years. The majority of patients in both ≥50 and <50 age groups received a non‐nucleoside reverse transcriptase inhibitor‐based regimen (89% vs. 87%), did not have AIDS at baseline (63% vs. 62%), and were male (59% vs. 58%). Older patients had a higher risk of death (adjusted hazard ratio (aHR) 1.64; 95% confidence intervals (CI): 1.48 to 1.83) and a lower risk of virologic failure (aHR: 0.73; 95% CI: 0.63 to 0.84). There was no difference in risk of ART modification (aHR: 1.00; 95% CI: 0.94 to 1.06). Risk factors for death, virologic failure and treatment modification were similar for each group.ConclusionsOlder age at ART initiation was associated with increased mortality and decreased risk of virologic failure in our cohort of more than 26,000 ART initiators in Latin America and the Caribbean. To the best of our knowledge this is the first study from the region to evaluate ART outcomes in this growing and important population. Given the complexity of issues related to ageing with HIV, a greater understanding is needed in order to properly respond to this shifting epidemic.

Modification of antiretroviral therapy regimen: Incidence and predictors in two major HIV/AIDS treatment centers in the Southwest Region of Cameroon

Background: The effectiveness of the first regimen of antiretroviral therapy (ART) is a major key to long-term success and sustainability of HIV treatment program. Aims: The objectives of this study were to determine the incidence rate, reasons, and factors associated with modification of initial ART regimen. Methods: A total of 502 patient files were reviewed. Modification of ART regimen was defined as either substitution or switch of a single drug in the regimen. Results: The total duration of follow-up was 629.8 person-years (PYs) over a median follow-up period of 37 months. About 92 (18.2%) of patients had their initial ART regimen modified, with a resulting incidence rate of modification at 14.6/100 PYs. Drug unavailability 49 (53.3%), drug toxicity 16 (17.4%), treatment failure 10 (10.9%), nonadherence 7 (7.6%), and concomitant condition 7 (7.6%) were common reasons for ART modifications. In the adjusted multivariate Cox proportional hazard model, the type of initial ART regimen (zidovudine/lamivudine (3TC)/efavirenz vs. tenofovir/3TC/nevirapine (NVP), aHR 4.78, 95% confidence interval [CI] [1.42, 16.12], P = 0.012), and duration on regimen (≤1 year vs. >3 years, aHR 4.11, 95% CI [1.02–9.22], P = 0.0001) were significantly associated with modification of initial ART regimen. Conclusion: Our findings indicate that the incidence rate of initial ART regimen modification was high. Hence, implementing better health systems to ensure a steady supply of drugs as well as early HIV diagnosis and ART initiation will reduce the rate of regimen change.

Incidence and Predictors of Antiretroviral Treatment Modification in HIV-Infected Adults: A Brazilian Historical Cohort from 2001 to 2010.

This study estimated the incidence of and time to first antiretroviral therapy (ART) modification. This longitudinal analysis comprised a sample of 236 patients from three HIV/AIDS referral centers in Belo Horizonte, Brazil—part of a major historical cohort. Inclusion criteria were as follows: having been treatment-naive patient ≥18 years old who initiated ART between 2001 and 2005 in these three referral centers. The main endpoint was time to first ART modification. Patients were followed up for five years, covering the period 2001–2010, during which time Pearson's chi-square test was performed to compare ART modification between groups. Kaplan-Meier inverse survival curves were employed to describe the probability of ART modification and Cox proportional hazard regression was used to estimate the adjusted hazard ratio (aHR) of ART modification. Among 247 patients from the major cohort, 236 were eligible. Median follow-up time was 37.2 months and the contribution in person-months was 7,615.4 months. A total of 108 (45.8%) patients had their ART regimen modified at least once (incidence rate: 1.42 per 100 person-months). Adverse drug reactions were the main reason for ART modification. Women (aHR = 1.62; p = 0.022) and patients on protease inhibitor- (PI-) based regimens (aHR = 2.70; p < 0.001) were at higher risk of ART modification.

Modification of First-line Antiretroviral Therapy in Treatment-naive, HIV Positive Patients

Introduction: Modification of initial Antiretroviral Therapy (ART) program is an important issue in HIV infected patients as the number of ART regimens available is limited. Hence, there is a need to understand the factors that affect modification and therefore, the durability of the initial antiretroviral regimen. Aim: To study the type of modification of first line ART in treatment-naive HIV positive patients and factors influencing it. Materials and Methods: A retrospective observational study was carried out in the HIV clinic of a tertiary care hospital, using data obtained from the case records of the subjects who were initiated on ART between January 2012 to December 2014. Data on patient baseline characteristics, proportion of patients who required modification, type and time of modification was collected. The determinants of time to modification were analysed using Chi-square test. Binomial logistic regression was utilized to assess independent risk factors for change in regimen. Results: Out of 200 case records analysed, 54 patients had to undergo a modification in their initial regimen. The mean age of patients was 44.68 ± 11.31 years. Majority of the patients were males. The most common reason for modification was Adverse Drug Reactions (ADRs) (79.63%) followed by treatment failure (9.25%). In 85.18% cases, modification involved substitution. Occurrence of ADRs and non-tenofovir based first-line regimens were associated with higher likelihood of substitution in regimen (p<0.05). The median time (IQR) to modification was 173 (152.25, 293.50) days. Conclusion: ADRs and the use of non-tenofovir based regimens resulted in significantly higher rates of modification of antiretroviral therapy. There should be monitoring of patients on ART to detect ADRs at the earliest and to obtain increased use of single tablet containing tenofovir based regimen to improve durability of first line regimens.

Analysis of antiretroviral therapy modification in routine clinical practice in the management of HIV infection

ObjectivesThe main goal was to assess the reasons for antiretroviral therapy (ART) change in patients with HIV in a hospital setting in routine clinical practice. The economic impact of ART...

Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia.

Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population. Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity. Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality.

Factors associated with the first antiretroviral therapy modification in older HIV-1 positive patients.

BackgroundRates of first antiretroviral therapy (cART) modifications are high in most observational studies. The age-related differences in treatment duration and characteristics of first cART modifications remain underinvestigated. With increasing proportion of older patients in HIV population it is important to better understand age-related treatment effects.MethodsPatients were included into this analysis, if being cART naïve at the first visit at the clinic. Follow-up time was measured from the first visit date until first cART modification or 28 February 2013. First cART modification was defined as any change in the third drug component i.e. protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), integrase inhibitor or fusion inhibitor. Cox proportional hazard models were used to identify factors related to first cART modification in three age groups: <30, 30–50 and >50.ResultsIn total 2027 patients with 14,965 person-years of follow-up (PYFU) were included. The oldest group included 136 patients with 1901, middle group 1202 with 8416 PYFU and youngest group consisted of 689 patients with 4648 PYFU. Median follow-up time was 5.8 (IQR 3.4–9.4) years, median time on first cART was 4.4 (IQR 2.1–8.5) years. 72.4 % of patients started PI-based and 26.1 % NNRTI-based regimen. In total 1268 (62.5 %) patients had cART modification (non-adherence 30.8 %, toxicity 29.6 %). Durability of first cART was the best in patients over 50 y.o. (log-rank test, p = 0.001). Factors associated with discontinuation in this group were late presentation (HR 0.45, [95 % CI 0.23–0.90], p = 0.02) and PI use (HR 2.17, [95 % CI 1.18–4.0], p = 0.01).ConclusionsRates of first cART modifications or discontinuation were comparable in all groups; however older patients were significantly longer on first cART regimen.

Plasma Mitochondrial DNA Levels as a Biomarker of Lipodystrophy Among HIV-infected Patients Treated with Highly Active Antiretroviral Therapy (HAART).

Lipodystrophy is a common complication in HIV-infected patients taking highly active antiretroviral therapy. Its early diagnosis is crucial for timely modification of antiretroviral therapy. We hypothesize that mitochondrial DNA in plasma may be a potential marker of LD in HIV-infected individuals. In this study, we compared plasma mitochondrial DNA levels in HIV-infected individuals and non-HIV-infected individuals to investigate its potential diagnostic value.Total plasma DNA was extracted from 67 HIV-infected patients at baseline and 12, 24 and 30 months after initiating antiretroviral therapy. Real-time quantitative PCR was used to determine the mitochondrial DNA levels in plasma. Lipodystrophy was defined by the physician-assessed presence of lipoatrophy or lipohypertrophy in one or more body regions.The mitochondrial DNA levels in plasma were significantly higher at baseline in HIV-infected individuals than in non-HIV-infected individuals (p<0.05). At month 30, 33 out of 67 patients (49.2%) showed at least one sign of lipodystrophy. The mean plasma mitochondrial DNA levels in lipodystrophy patients were significantly higher compared to those without lipodystrophy at month 24 (p<0.001). The receiver operating curve analysis demonstrated that using plasma mitochondrial DNA level (with cut-off value >5.09 log10 copies/ml) as a molecular marker allowed identification of patients with lipodystrophy with a sensitivity of 64.2% and a specificity of 73.0%.Our data suggest that mitochondrial DNA levels may help to guide therapy selection with regards to HIV lipodystrophy risk.

Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients.

The goal of antiretroviral therapy (ART) is to reduce HIV-related morbidity and mortality by suppressing HIV replication. The prognostic value of persistent low-level viremia (LLV), particularly for clinical outcomes, is unknown. Assess the association of different levels of LLV with virological failure, AIDS event, and death among HIV-infected patients receiving combination ART. We analyzed data from 18 cohorts in Europe and North America, contributing to the ART Cohort Collaboration. Eligible patients achieved viral load below 50 copies/ml within 3-9 months after ART initiation. LLV50-199 was defined as two consecutive viral loads between 50 and 199 copies/ml and LLV200-499 as two consecutive viral loads between 50 and 499 copies/ml, with at least one between 200 and 499 copies/ml. We used Cox models to estimate the association of LLV with virological failure (two consecutive viral loads at least 500 copies/ml or one viral load at least 500 copies/ml, followed by a modification of ART) and AIDS event/death. Among 17 902 patients, 624 (3.5%) experienced LLV50-199 and 482 (2.7%) LLV200-499. Median follow-up was 2.3 and 3.1 years for virological and clinical outcomes, respectively. There were 1903 virological failure, 532 AIDS events and 480 deaths. LLV200-499 was strongly associated with virological failure [adjusted hazard ratio (aHR) 3.97, 95% confidence interval (CI) 3.05-5.17]. LLV50-199 was weakly associated with virological failure (aHR 1.38, 95% CI 0.96-2.00). LLV50-199 and LLV200-499 were not associated with AIDS event/death (aHR 1.13, 95% CI 0.81-1.68; and aHR 0.95, 95% CI 0.62-1.48, [corrected] respectively). LLV200-499 was strongly associated with virological failure, but not with AIDS event/death. Our results support the US guidelines, which define virological failure as a confirmed viral load above 200 copies/ml.