Prevalence and associated factors of treatment failure among HIV/AIDS patients on HAART attending University of Gondar Referral Hospital Northwest Ethiopia

Background

The initiation of highly active antiretroviral therapy (HAART) plays a significant role in the clinical management of HIV infected people by preventing morbidity and mortality. This benefit becomes, the most terrible when treatment failure develops. Thus, this research aims to assess the prevalence and associated factors of treatment failure among HIV/AIDS patients on HAART attending University of Gondar Referral Hospital Northwest Ethiopia.

Results

Patients on ART with a minimum of 6?months and up to 12?years of treatment were being enrolled. The prevalence of treatment failure, immunological failure and virological failure among people living with HIV/AIDS attending University of Gondar referral hospital were 20.3, 13.2, and 14.7%, respectively. Patients who had no formal education (Adjusted odds ratio (AOR): 3.8; 95% CI, 1.05–13.77), primary level education (AOR: 4.2; 95% CI, 1.16–15.01) and duration on ART <?6?years (AOR: 2.1; 95%CI, 1.12–3.81) were a significant risk factor. However, initial adult regimen D4T?+? 3TC+ EFV (AOR: 0.025; 95% CI, 0.002–0.36), AZT +3TC?+?NVP (AOR: 0.07; 95% CI, 0.01–0.71), AZT?+? 3TC?+?EFV (AOR: 0.046; 95% CI, 0.004–0.57) andTDF+3TC?+?EFV (AOR: 0.04; 95% CI, 0.004–0.46) were significantly protective for treatment failure.

Conclusions

Timely and early identification of associated factors and monitoring antiretroviral therapy treatment failure should be done to enhance the benefit and to prevent further complication of the patients. It is preferable to initiate ART using any one of the following ART regimens: AZT +3TC?+?NVP, AZT?+?3TC?+?EFV and TDF?+?3TC?+?EFV to prevent treatment failure. Since the prevalence of this treatment failure and its associated factor may be different from other ART centers and community in Ethiopia, further national representative institutional based cross-sectional researches are needed across all ART centers of Ethiopia in order to determine the prevalence of treatment failure and its associated factors.

     

Meta-analysis of two randomized controlled trials comparing combined zidovudine and didanosine therapy with combined zidovudine, didanosine, and nevirapine therapy in patients with HIV. INCAS study team

OBJECTIVES: To extend the range of CD4 counts in which a plasma viral load nadir (pVL) <20 copies/ml was known to be predictive of the duration of virologic response. To determine whether baseline pVL is predictive of virologic response during the study periods. METHODS: A meta-analysis was conducted of the original individual patient data from two randomized controlled trials comparing zidovudine (ZDV)/didanosine (ddI) with ZDV/ddI/nevirapine (NVP). RESULTS: In total, 87 patients received ZDV/ddI and 83 received ZDV/ddI/NVP. Study subjects on triple therapy with baseline pVL <100,000 copies/ml were more likely to achieve a pVL <400 copies/ml (odds ratio [OR] = 2.49; p = .02) and <20 copies/ml (OR = 4.76; p = .001) during the trial than those with baseline pVL > 100,000 copies/ml. Among triple therapy patients, the relative risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log10 copies/ ml; p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure associated with pVL nadir <20 copies/ml and between 21 and 400 copies/ml were .04 (p = .0001) and .56 (p = .26), respectively, compared with patients with a pVL nadir >400 copies/ml. CONCLUSIONS: We have extended our earlier results that achieving a pVL nadir <20 copies/ml is important for maintaining virologic suppression. In particular, we have demonstrated that a pVL nadir <20 copies/ml is at least fivefold more protective against virologic failure than achieving a pVL nadir between 20 and 400 copies/ml. Baseline pVL is significantly associated with the probability of achieving and sustaining virologic suppression.     

Effectiveness and safety of abacavir, lamivudine, and zidovudine in antiretroviral therapy-naive HIV-infected patients: results from a large multicenter observational cohort

OBJECTIVE: To analyze the safety and effectiveness of abacavir, lamivudine, and zidovudine (ABC/3TC/ZDV) in antiretroviral therapy (ART)-naive HIV-infected patients. DESIGN: Retrospective observational cohort study. METHODS: We analyzed all consecutive ART-naive HIV-infected patients who initiated ABC/3TC/ZDV in 71 centers throughout Spain and had a clinical visit and laboratory data at least 16 weeks after initiating this regimen. We assessed safety, mortality, new AIDS-defining conditions (ADCs) and treatment failure, the latter defined by any of the following: (1) reduction in plasma HIV-1 viral load (pVL) <1 log during the first 12 weeks of ART, unless it was less than the lower limit of quantification (LOQ); (2) failure to achieve a pVL or = LOQ after achieving a pVL 相似文献   

Early Virologic Response to Abacavir/Lamivudine and Tenofovir/Emtricitabine During ACTG A5202

Abstract

Background: ACTG A5202 randomized treatment-naïve individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC. Objective: To compare regimen-specific early virologic response. Methods: Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (N = 1,813) and from entry to week 1, 2, and 4 in substudy subjects (n = 179). We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional hazards models. Results: TDF/FTC and ABC/3TC produced similar week 4 VL declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median -2.1 vs -1.9 log₁₀ copies/mL; P < .001). In the substudy of subjects with week 1, 2, and 4 VL data, there was no difference in VL decline in individuals randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller week 4 VL decline was associated with increased risk of virologic failure. Conclusions: Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity.     

Prevalence and risk factors for developing K65R mutations among HIV-1 infected patients who fail an initial regimen of fixed-dose combination of stavudine, lamivudine, and nevirapine.

BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine (d4T/3TC/NVP) is extensively used as initial antiretroviral regimen in developing countries. K65R mutations that occur after failing this regimen prevent the use of tenofovir, didanosine, and abcavir in the second-line regimen. OBJECTIVES: To determine the prevalence and risk factors of K65R mutations after failing d4T/3TC/NVP. STUDY DESIGN: Genotypic resistance testing was conducted among HIV-1 infected patients who experienced virological failure with an initial regimen of d4T/3TC/NVP. RESULTS: There were 122 patients who received antiretroviral therapy (ART) for a median (IQR) duration of 19 (13-27) months. Median (IQR) CD4 cell count and plasma HIV-1 RNA at virological failure was 174 (109-264) cells/mm(3) and 4.0 (3.7-4.6)log copies/mL, respectively. The prevalence of K65R mutations was 7%. Patients with K65R mutations had higher plasma HIV-1 RNA at virological failure compared to patients without K65R mutations (4.9log copies/mL vs. 4.0log copies/mL, p=0.001). By logistic regression analysis only plasma HIV-1 RNA at failure correlated with the occurrence of K65R mutations [OR 4.2 (95% CI, 1.5-11.2) per 0.5log copies/mL increment of HIV-1 RNA]. CONCLUSIONS: Seven percent of patients had K65R mutations after failing an initial d4T/3TC/NVP regimen. Tenofovir, didanosine, and abcavir cannot be used in second-line regimen for these patients. HIV-1 RNA at the time that virological failure was detected correlated with the occurrence of K65R mutations.     

Predictors of antiretroviral treatment failure in an urban HIV clinic

BACKGROUND: Predictors of antiretroviral treatment (ART) failure are not well characterized for heterogeneous clinic populations. METHODS: A retrospective analysis was conducted of HIV-infected patients followed in an urban HIV clinic with an HIV RNA measurement < or =400 copies/mL on ART between January 1, 2003, and December 31, 2004. The primary endpoint was treatment failure, defined as virologic failure (> or =1 HIV RNA measurement >400 copies/mL), unsanctioned stopping of ART, or loss to follow-up. Prior ART adherence and other baseline patient characteristics, determined at the time of the first suppressed HIV RNA load on or after January 1, 2003, were extracted from the electronic health record (EHR). Predictors of failure were assessed using proportional hazards modeling. RESULTS: Of 829 patients in the clinic, 614 had at least 1 HIV RNA measurement < or =400 copies/mL during the study period. Of these, 167 (27.2%) experienced treatment failure. Baseline characteristics associated with treatment failure in the multivariate model were: poor adherence (hazard ratio [HR] = 3.44; 95% confidence interval [CI]: 2.34 to 5.05), absolute neutrophil count <1000/mm (HR = 2.90, 95% CI: 1.26 to 6.69), not suppressed on January 1, 2003 (HR = 2.69, 95% CI: 1.78 to 4.07) or <12 months of suppression (HR = 1.64, 95% CI: 1.10 to 2.45), CD4 count <200 cells/mm (HR = 1.90, 95% CI: 1.31 to 2.76), nucleoside-only regimen (HR = 1.75, 95% CI: 1.08 to 2.82), prior virologic failure (HR = 1.70, 95% CI: 1.22 to 2.39) and > or =1 missed visit in the prior year (HR = 1.56, 95% CI: 1.13 to 2.16). CONCLUSIONS: More than one quarter of patients in a heterogeneous clinic population had treatment failure over a 2-year period. Prior ART adherence and other EHR data readily identify patient characteristics that could trigger specific interventions to improve ART outcomes.     

Induction with abacavir/lamivudine/zidovudine plus efavirenz for 48 weeks followed by 48-week maintenance with abacavir/lamivudine/zidovudine alone in antiretroviral-naive HIV-1-infected patients

BACKGROUND: The ESS40013 study tested 4-drug induction followed by 3-drug maintenance as initial antiretroviral therapy (ART) to reduce HIV RNA rapidly and then to simplify to an effective yet more convenient and tolerable regimen. METHODS: Four hundred forty-eight antiretroviral-naive adults were treated with abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) and efavirenz (EFV) for the 48-week induction phase. Two hundred eighty-two patients were randomized in a 1:1 ratio to continue ABC/3TC/ZDV+EFV or to simplify to ABC/3TC/ZDV for the 48-week maintenance phase. RESULTS: The baseline median HIV RNA level and CD4 cell count were 5.08 log10 copies/mL (56%>or=100,000 copies/mL) and 210 cells/mm (48% <200 cells/mm), respectively. No significant differences were noted between ABC/3TC/ZDV+EFV and ABC/3TC/ZDV for an HIV RNA level <50 copies/mL (79% vs. 77% [intent to treat (ITT), missing=failure]; P=0.697) or time to treatment failure (P=0.75) at week 96. Drug-related adverse events were more commonly reported for ABC/3TC/ZDV+EFV than for ABC/3TC/ZDV (15% vs. 6%). Improvements in total cholesterol, low-density lipoprotein cholesterol, and triglycerides were observed in the ABC/3TC/ZDV group. Virologic failure occurred in 22 patients during induction and in 24 patients (16 in ABC/3TC/ZDV group and 8 in ABC/3TC/ZDV+EFV group; P=0.134) during maintenance. A greater proportion of patients receiving ABC/3TC/ZDV than ABC/3TC/ZDV+EFV reported perfect adherence at week 96 (88.8% vs. 79.6%; P=0.057). CONCLUSIONS: After induction with ABC/3TC/ZDV+EFV, simplification to ABC/3TC/ZDV alone maintained virologic control and immunologic response, reduced fasting lipids and ART-associated adverse events, and improved adherence.     

Tenofovir disoproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients: virologic, immunologic, and morphologic changes--a 96-week analysis

BACKGROUND: In antiretroviral-naive patients, tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) demonstrated superior outcomes compared with fixed-dose zidovudine (ZDV)/lamivudine (3TC) and EFV through 48 weeks. Results through a 96-week extension phase are presented. METHODS: In this randomized, open-label, noninferiority trial, 517 antiretroviral-naive HIV-infected patients received TDF, FTC, and EFV (TDF + FTC + EFV) or ZDV/3TC and EFV (ZDV/3TC + EFV). The primary endpoint was the proportion of patients with an HIV RNA level <400 copies/mL in patients without baseline nonnucleoside resistance. RESULTS: Through week 96, significantly more patients receiving TDF + FTC + EFV achieved and maintained an HIV RNA level <400 copies/mL (75% receiving TDF + FTC + EFV vs. 62% receiving ZDV/3TC + EFV; P = 0.004). There was a trend toward greater virologic suppression to <50 copies/mL in the TDF + FTC + EFV group (67% vs. 61%; P = 0.16). The TDF + FTC + EFV group demonstrated a significantly greater increase in CD4 count (270 vs. 237 cells/mm; P = 0.036). No patient developed the K65R mutation. Limb fat at week 96 was significantly greater in the TDF + FTC + EFV group versus the ZDV/3TC + EFV group (7.7 vs. 5.5 kg; P < 0.001). CONCLUSION: Over 96 weeks, the combination of TDF, FTC, and EFV was superior to fixed-dose ZDV/3TC + EFV for achieving and maintaining an HIV RNA level <400 copies/mL and an increase in CD4 cells.     

Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults: results of the Ziagen Once Daily in Antiretroviral Combination Study

The long intracellular half-life of abacavir (ABC) supports its once-daily use, and this would be expected to simplify treatment if ABC could be given as part of a complete once-daily regimen. A randomized double-blind clinical trial compared the efficacy and safety of 600 mg of ABC administered once daily (n = 384) versus 300 mg of ABC administered twice daily (n = 386) in combination with 300 mg of lamivudine (3TC) and 600 mg of efavirenz (EFV) administered once daily in antiretroviral-naive patients over 48 weeks. The baseline median plasma HIV-1 RNA level was 4.89 log10 copies/mL (44% with viral load >100,000 copies/mL), and the median CD4 cell count was 262 cells/mm. ABC administered once daily was non-inferior to the twice-daily regimen, with 66% and 68% of patients in these respective treatment arms achieving a confirmed plasma HIV-1 RNA level <50 copies/mL (95% confidence interval: -8.4%, 4.9%). The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure (10% vs. 8%), emergence of resistance mutations, CD4 cell increases from baseline (median, 188 vs. 200 cells/mm), safety profile, and incidence of ABC-related hypersensitivity reactions (9% vs. 7%). ABC administered once daily in combination with 3TC and EFV administered once daily was non-inferior to the ABC twice-daily dosing schedule when combined with 3TC and EFV over 48 weeks.     

Ecological Study of the Predictors of Successful Management of Dyslipidemia in HIV-Infected Patients on ART: the Swiss HIV Cohort Study

Abstract

Purpose: Antiretroviral therapy (ART) may induce metabolic changes and increase the risk of coronary heart disease (CHD). Based on a health care system approach, we investigated predictors for normalization of dyslipidemia in HIV–infected individuals receiving ART. Method: Individuals included in the study were registered in the Swiss HIV Cohort Study (SHCS), had dyslipidemia but were not on lipidlowering medication, were on potent ART for ≥3 months, and had ≥2 follow-up visits. Dyslipidemia was defined as two consecutive total cholesterol (TC) values above recommended levels. Predictors of achieving treatment goals for TC were assessed using Cox models. Results: Analysis included 958 individuals with median followup of 2.3 years (IQR 1.2–4.0). 454 patients (47.4%) achieved TC treatment goals. In adjusted analyses, variables significantly associated with a lower hazard of reaching TC treatment goals were as follows: older age (compared to 18–37 year olds: hazard ratio [HR] 0.62for 45–52 year olds, 95% CI 0.47–0.82; HR 0.40 for 53–85, 95% CI 0.29–0.54), diabetes (HR 0.39, 95% CI 0.26–0.59), history of coronary heart disease (HR 0.27, 95% CI 0.10–0.71), higher baseline TC (HR 0.78, 95% CI 0.71–0.85), baseline triple nucleoside regimen (HR0.12 compared to PI–only regimen, 95% CI 0.07–0.21), longer time on PI–only regimen (HR 0.39, 95% CI 0.33–0.46), longer time on NNRTI only regimen (HR 0.35, 95% CI 0.29–0.43), and longer time on PI/NNRTI regimen (HR 0.34, 95% CI 0.26–0.43). Switching ART regimen when viral load was undetectable was associated with a higher hazard of reaching TC treatment goals (HR 1.48, 95% CI 1.14–1.91). Conclusion: In SHCS participants on ART, several ART–related and not ART-related epidemiological factors were associated with insufficient control of dyslipidemia. Control of dyslipidemia in ART recipients must be further improved.     

Response to efavirenz-containing regimens in previously antiretroviral-naive HIV-positive patients: the role of gender

BACKGROUND: We investigated the role of gender on response to efavirenz (EFV)-containing regimens in previously antiretroviral-naive patients. METHODS: All previously antiretroviral-naive individuals from the Royal Free Hospital in London starting EFV from 1996 onward were included. Treatment failure was defined as the first of 2 consecutive viral load measurements >500 copies/mL more than 24 weeks after starting EFV. Standard survival methods were used to assess time to discontinuation and to treatment failure. RESULTS: Ninety-six women and 337 men were included. Women were mostly of black African ethnicity (64.6%) with a heterosexual risk (94.8%), whereas men were mostly white (66.8%; P < 0.0001) with a homosexual risk (71.2%; P < 0.0001). Women had lower CD4 counts when starting EFV (median [interquartile range [IQR] = 126 [36, 220] cells/mm for women vs. 190 [109, 268] cells/mm for men; P = 0.0003). After 48 and 96 weeks, 38.8% (95% confidence interval [CI]: 28.8% to 48.7%) and 56.3% (95% CI: 45.8% to 66.9%) of women had discontinued EFV compared with 28.3% (95% CI: 23.4% to 33.2%) and 41.8% (95% CI: 36.3% to 47.3%) of men (P = 0.005). The percentage experiencing failure by 48 and 96 weeks when ignoring treatment changes but censoring at the date of discontinuing all treatment was 1.3% (0.0%, 3.9%) and 4.4% (0.0%, 9.3%) for women compared with 3.8% (1.6%, 6.0%; P = 0.49) and 5.8% (3.0%, 8.6%) for men. Median (IQR) CD4 count increases at 48 weeks were +166 (+89, +239) cells/mm for women and +176 (+93, +263) cells/mm for men. CONCLUSIONS: Women seem to have comparable virologic and immunologic outcomes to first-line EFV-containing regimens compared with men, although they are more likely to discontinue the drug.     

艾滋病临床用药分析

目的 探讨艾滋病临床用药方案与CD4细胞的关系,以期为艾滋病后续治疗起到积极的理论支持。方法 选取某临床医院2012年12月~2017年10月统计的732例艾滋病患者基线和随访数据,分析所有患者基线及随访治疗方案,将CD4个数作为评判标准,主要研究基线治疗以及随访治疗后患者CD4细胞个数的变化情况。结果 临床数据中患者的所有治疗方案中,有五组治疗方案:3TC+AZT+EFV、3TC+AZT+NVP、3TC+D4T+EFV、3TC+D4T+NVP和3TC+TDF+EFV占总方案的93.03%,且其中我国抗HIV治疗方案主要应用3TC+AZT+EFV和3TC+D4T+EFV,全部数据中未换药组占比79.97%;在治疗过程中,CD4提高的患者占64.30%。结论 艾滋病临床治疗中,治疗方案3TC+AZT+EFV、3TC+AZT+NVP、3TC+D4T+EFV、3TC+D4T+NVP和3TC+TDF+EFV被广泛应用,我国临床治疗以方案3TC+AZT+EFV和3TC+D4T+EFV为主,且各种治疗方案对于HIV病情有相对较好的稳定作用。     

Effectiveness of first-line antiretroviral therapy in the IPEC cohort,Rio de Janeiro,Brazil

Background

While Brazil has had a long-standing policy of free access to antiretroviral therapy (ART) for all in need, the epidemiological impact of ART on human immunodeficiency virus (HIV) RNA suppression in this middle-income country has not been well evaluated. We estimate first-line ART effectiveness in a large Brazilian cohort and examine the socio-demographic, behavioral, clinical and structural factors associated with virologic suppression.

Methods

Virologic suppression on first-line ART at 6, 12, and 24 months from start of ART was defined as having a viral load measurement ≤400 copies/mL without drug class modification and/or discontinuation. Drug class modification and/or discontinuation were defined based on the class of a particular drug. Quasi-Poisson regression was used to quantify the association of factors with virologic suppression.

Results

From January 2000 through June 2010, 1311 patients started first-line ART; 987 (75%) patients used NNRTI-based regimens. Virologic suppression was achieved by 77%, 76% and 68% of patients at 6, 12 and 24 months, respectively. Factors associated with virologic suppression at 12 months were: >8 years of formal education (compared to <4 years, risk ratio (RR) 1.13, 95% confidence interval (95% CI) 1.03-1.24), starting ART in 2005-2010 (compared to 2000-2004, RR 1.25 95% CI 1.15-1.35), and clinical trial participation (compared to no participation, RR 1.08 95% CI 1.01-1.16). Also at 12 months, women showed less virologic suppression compared to heterosexual men (RR 0.90 95% CI 0.82-0.99). For the 24-month endpoint, in addition to higher education, starting ART in the later period, and clinical trial participation, older age and an NNRTI-based regimen were also independently associated with virologic suppression.

Conclusions

Our results show that in Brazil, a middle-income country with free access to treatment, over three-quarters of patients receiving routine care reached virologic suppression on first-line ART by the end of the first year. Higher education, more recent ART initiation and clinical trial participation were associated with improved outcomes both for the 12-month and the 24-month endpoints, suggesting that further studies are needed to understand what aspects relating to these factors lead to higher virologic suppression.