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.

     

Hepatotoxicity from first line antiretroviral therapy: an experience from a resource limited setting

Background

Highly active antiretroviral therapy (HAART) has been associated with liver toxicity. The role of monitoring for liver toxicity has not been well studied in resource-limited settings (RLS).

Objectives

To determine the background prevalence and incidence of liver injury and describe the associated signs and symptoms of acute hepatitis after initiating HAART; and to determine the role of liver enzyme tests in monitoring hepatotoxicity.

Methods

In this prospective study, in Mulago Hospital AIDS Clinics, we consecutively enrolled adult patients initiated on one of three first line HAART regimens [Stavudine (d4T)-Lamivudine (3TC) and nevirapine (NVP); Zidovudine (AZT)-3TC and Efavirenz (EFV) or d4T-3TC-EFV]. We monitored ALT (alanine aminotransferase) and clinical evidence of acute hepatitis at baseline, 2^nd, 6^th, 10^th and 14^th week of therapy.

Results

Two hundred and forty HIV-positive HAART- naïve patients were enrolled in the study. The baseline prevalence of transaminitis was 1.7% with an incidence of 4.2% at 14 weeks. Grade 3–4 hepatotoxicity was documented in 1.3%. Jaundice was seen in grade 2–4 ALT elevations. Being on concurrent HAART and antituberculous drugs was associated with grade 2–4 toxicity compared to those who were only on HAART [OR; 16.0 (95% CI; 2.4–104.2)].

Conclusions

Incidence of severe hepatotoxicity within three months of first-line antiretroviral therapy was low, suggesting that routine measurement of transaminases may not be necessary in all patients initiating HAART in RLS. Routine measurement may be important in following patients on HAART and concurrent TB treatment as well as those with jaundice to avoid missing hepatotoxicity.     

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。     

Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.     

Lipodystrophy and dyslipidemia among patients taking first-line, World Health Organization-recommended highly active antiretroviral therapy regimens in Western India

OBJECTIVE: To determine the prevalence of lipodystrophy, dyslipidemia, and hyperglycemia among HIV-infected patients taking long-term, first-line, World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens in India. DESIGN:: Cross-sectional study. METHODS: Asymptomatic, antiretroviral-naive patients and those treated for > 1 year with zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) and stavudine (d4T)/3TC/NVP were subjectively assessed for lipodystrophy (lipoatrophy, lipohypertrophy, and mixed patterns), and lipid profiles were determined after an overnight fast. The US National Cholesterol Education Program III guidelines were used to define dyslipidemia (total cholesterol > or = 200 mg/dL, low-density lipoprotein cholesterol > or = 130 mg/dL, triglycerides > or = 150 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, and total cholesterol/high-density lipoprotein cholesterol ratio > or = 6.5). Prevalence and risk factors associated with these complications were determined. RESULTS: Of the 306 patients (126 controls, 30 on ZDV/3TC/NVP, and 150 on d4T/3TC/NVP), the prevalence of lipodystrophy was 46.1%, and lipoatrophy was significantly associated with d4T use. The prevalence of dyslipidemia and fasting hyperglycemia was significantly higher in the treatment groups. Proportion of patients with high-density lipoprotein > or = 60 mg/dL was significantly higher in the treatment groups; however, this had little impact on the total cholesterol/high-density lipoprotein ratio. CONCLUSION: There is a high prevalence of lipodystrophy, dyslipidemia, and hyperglycemia in patients taking long-term WHO-recommended generic HAART in western India. Interventions to address these complications need to be incorporated into antiretroviral scale-up programs, including improving access to alternative less-offending drugs like tenofovir and abacavir.     

Opportunistic infections in relation to antiretroviral status among AIDS patients from south India

Background: There is a need to generate data from India on relative frequencies of specific opportunistic infections (OIs) in different regions and their relation to the choice of commonly used generic highly active anti-retroviral therapy (HAART) regimens. Objectives: To document the prevailing prevalence pattern of OIs both before and after HAART, to look for reduction in OIs following HAART, to assess the risk of developing new OIs within 6 months of HAART initiation and to see if there is any difference in the risk of developing a new OI within 6 months of HAART initiation, for those on Efavirenz (EFV)-based regimens and Nevirapine (NVP)-based regimens. Materials and Methods: In a prospective observational cohort study conducted in South India involving 108 ART-naive AIDS patients, different pathogens were isolated and identified using standard laboratory techniques. Data analysis was done using SPSS software (version 16.0). Risk of developing an OI after HAART initiation was assessed using the likelihood ratio test from Cox regression models. Results: Tuberculosis (53.4%), oral Candidiasis (27.2%) and Herpes Zoster (14.7%) were the common infections seen. There was a drastic reduction of 96.59% in OI events after 6 months of HAART. The risk of developing an OI within 6 months of HAART initiation was 5.56%. Time to development of an OI in the first 6 months of HAART was shorter for the NVP-based regimens than with EFV-based regimens, but this difference was not statistically significant (HR=0.891, 95% CI: 0.179–4.429; P=0.888). Conclusion: Tuberculosis is the most important OI before initiation of HAART. Both EFV and NVP-based regimens are equally efficacious in controlling OIs.     

Lipid Changes in Patients Initiating Efavirenz- and Indinavir-Based Antiretroviral Regimens

Abstract

Purpose: To evaluate nonfasting lipid levels in a large cohort of patients on three HAART regimens: efavirenz + zidovudine + lamivudine (EFV+ZDV+3TC), efavirenz + indinavir (EFV+IDV), and indinavir + zidovudine + lamivudine (IDV+ZDV+3TC). Method: Nonfasting lipid levels were analyzed from a large randomized multicenter treatment trial for HIV-infected patients initiating HAART. Treatment evaluations were carried out at prescribed intervals, and data were recorded and analyzed. Assessment was limited to high-density lipoprotein (HDL) and total cholesterol. Results: The results demonstrate an increase in the total cholesterol, ranging from 23 to 57 mg/dL, in the three combinations of HAART therapy. The increase was most significant in the EFV+IDV arm where the effects appear to be additive. HDL cholesterol also increased in all three arms, but the greatest increase was in the two groups containing EFV. In all three arms, the HDL cholesterol increased significantly in women while increases in men were seen only in the EFV-containing arms. Men taking either IDV-containing regimen had a greater increase in total cholesterol, and therefore the total/HDL cholesterol ratio rose significantly. Conclusion: EFV and IDV independently elevate lipid levels. Alterations in the lipid levels may lead to increased cardiovascular risk in men, possibly mitigated by elevations in HDL cholesterol. In addition, changes in HDL cholesterol were significantly different between men and women.     

Impact of nevirapine on lipid metabolism

Abnormal blood lipid profiles may be observed both in HIV-infected individuals who are untreated and in those receiving highly active antiretroviral therapy (HAART). Besides maintaining optimal control of HIV replication and the preservation of immunity, treatment regimens ideally should have minimal or no metabolic side-effects. Nevirapine (NVP)-based HAART has beneficial effects on the lipid profile, in both treatment-n?ive and treatment-experienced patients, unlike protease inhibitor (PI)-based HAART. In antiretroviral (ARV)-naive patients enrolled in the Fat Redistribution and Metabolic Substudy (FRAMS) of the Atlantic Study, the NVP-containing regimen increased total cholesterol, high density lipoprotein (HDL) cholesterol concentration and particle size and apolipoprotein A1 (apo A1) levels at 24 weeks. The changes in HDL cholesterol plasma levels were demonstrated to be sustained in a subset of 98 FRAMS patients at 96 weeks. Switching from a PI-containing regimen to a PI-sparing regimen containing NVP has likewise been shown to favorably alter lipid profiles in two open label studies. In one study, one or more lipid profile parameters (total cholesterol, low density lipoprotein [LDL] cholesterol, LDL particle size, very low density lipoprotein cholesterol [VLDL1] HDL cholesterol, HDL particle size) had reverted to normal after 24 weeks in significantly more NVP-treated patients than PI-treated patients (69% versus 23%, p < .05). The 12-month results from the Barcelona PI Switch Study indicated that NVP improved lipid profiles over 12 months after PI-treated patients were switched to NVP. In conclusion, first-line NVP treatment is associated with a favorable lipoprotein profile, i.e., an increase in HDL-cholesterol and apo A1 plasma levels The lipid profile observed in patients who are switched from a PI-based regimen to a NVP-based regimen improves in a very similar fashion. These favorable lipid profiles may be of clinical benefit in reducing the risk for coronary artery disease in HIV-1 infected patients who are receiving long-term antiretroviral therapy.