Effectiveness of highly active antiretroviral therapy among HIV-1 infected women

STUDY OBJECTIVE: To describe the impact of highly active antiretroviral therapy (HAART) on mortality, morbidity, and markers of HIV disease progression in HIV infected women. DESIGN: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. SETTING: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). PARTICIPANTS: A total of 1691 HIV seropositive women with a study visit after April 1996. MAIN RESULTS: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. CONCLUSIONS: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality.     

高效抗逆转录病毒治疗的不良反应

高效抗逆转录病毒治疗(HAART)的应用大大降低了艾滋病相关的发病率和死亡率。但是,所有的抗逆转录病毒药物都有短期的或者是长期的不良反应,例如高乳酸血症、乳酸酸中毒、肝脏毒性、高血糖、脂肪代谢异常、增加血友病患者出血的危险、骨质疏松以及皮疹等等,不良反应严重影响了HAART的临床应用。本文就以上问题进行了综述。     

Estimation of body fat mass using dual-energy x-ray absorptiometry, bioelectric impedance analysis, and anthropometry in HIV-positive male subjects receiving highly active antiretroviral therapy

BACKGROUND: The purpose of this pilot study was to compare estimates of percentage body fat mass (FM) by bioelectric impedance analysis (BIA) and skinfold measurements (SF) with estimates obtained from dual-energy x-ray absorptiometry (DEXA) in 47 HIV-infected male subjects receiving highly active antiretroviral therapy (HAART). As different patterns of abdominal fat accumulation might affect the body FM estimation, correlation and agreement of these methods were also compared in patients with waist to hip ratio (WHR) < or =0.9 and >0.9. METHODS: Body FM was estimated by BIA and by measuring skinfold thickness at biceps, triceps, and subscapular area, and was compared with DEXA as the reference method using paired t-test. RESULTS: Estimates by SF were significantly higher and by BIA were significantly lower compared with DEXA for all subjects. This relationship persisted only in those with WHR >0.9. Both BIA and SF correlated significantly with DEXA, but they did not agree. However, both techniques showed a small intermethod bias, and the precision was within the acceptable range. This relationship persisted in those with WHR >0.9. In comparison with measurement by BIA, SF showed poorer agreement (larger bias and error). Conclusion: For population studies and perhaps to monitor changes over time for intervention studies, the bias for both BIA and SF methods is relatively small and errors and precisions are within the acceptable range when compared with DEXA, and thus all 3 techniques can be used for routine monitoring of total body FM in male subjects with HIV infection.     

Adherence to highly active antiretroviral therapy in Spain. A meta-analysis

Objectives

To estimate the percentage of adherence to highly-active antiretroviral therapy (HAART) in Spanish observational studies and to identify the variables associated with adherence.

Methods

Seven electronic databases were used to locate the studies. Six inclusion criteria were established. Two coders codified the variables independently. Intercoder reliability was calculated. Publication bias was analyzed through the Begg, Egger and Trim and Fill tests. Homogeneity was evaluated using the Q test and the l² index. A random effects model was assumed to estimate both the overall percentage of adherence and to explain heterogeneity.

Results

This meta-analysis included 23 observational studies, yielding a total of 34 adherence estimates. The sample was composed of 9,931 HIV-positive individuals (72% men) older than 18 years under treatment with HAART. The percentage of patients adhering to an intake of >90% of the prescribed antiretroviral drugs was 55%. Wide heterogeneity was detected (I² = 91.20; 95%CI: 88.75-93.13). Adherence was mainly measured using a single strategy (47.8%), the most widely used being self-report (48.7%). In the univariate analysis, the following factors were significant: infection stages A (β = 0.68, p <0.001) and B (β = -0.56, p <0.01), viral loads >200 copies/ml (β = -0.41, p <0.05) and <200 (β = 0.39, p <0.05), and university education (β = -0.66, p<0.05).

Conclusions

The overall percentage of adherence was 55%, although this value may be an overestimate. Adherence was associated with infection stage A and with a viral load of <200 copies/ml.     

The cost-effectiveness of counseling strategies to improve adherence to highly active antiretroviral therapy among men who have sex with men.

OBJECTIVE: Inadequate adherence to highly active antiretroviral therapy (HAART) may lead to poor health outcomes and the development of HIV strains that are resistant to HAART. The authors developed a model to evaluate the cost-effectiveness of counseling interventions to improve adherence to HAART among men who have sex with men (MSM). METHODS: The authors developed a dynamic compartmental model that incorporates HIV treatment, adherence to treatment, and infection transmission and progression. All data estimates were obtained from secondary sources. The authors evaluated a counseling intervention given prior to initiation of HAART and before all changes in drug regimens, combined with phone-in support while on HAART. They considered a moderate-prevalence and a high-prevalence population of MSM. RESULTS: If the impact of HIV transmission is ignored, the counseling intervention has a cost-effectiveness ratio of $25,500 per quality-adjusted life year (QALY) gained. When HIV transmission is included, the cost-effectiveness ratio is much lower: $7400 and $8700 per QALY gained in the moderate- and high-prevalence populations, respectively. When the intervention is twice as costly per counseling session and half as effective as estimated in the base case (in terms of the number of individuals who become highly adherent, and who remain highly adherent), then the intervention costs $17,100 and $19,600 per QALY gained in the 2 populations, respectively. CONCLUSIONS: Counseling to improve adherence to HAART increased length of life, modestly reduced HIV transmission, and cost substantially less than $50,000 per QALY gained over a wide range of assumptions but did not reduce the proportion of drug-resistant strains. Such counseling provides only modest benefit as a tool for HIV prevention but can provide significant benefit for individual patients at an affordable cost.     

Micronutrients in HIV-positive persons receiving highly active antiretroviral therapy

In HIV-infected persons, low serum concentrations of vitamins and minerals, termed micronutrients, are associated with an increased risk of HIV disease progression and mortality. Micronutrient supplements can delay HIV disease progression and reduce mortality in HIV-positive persons not receiving highly active antiretroviral therapy (HAART). With the transition to more universal access to HAART, a better understanding of micronutrient deficiencies and the role of micronutrient supplements in HIV-positive persons receiving HAART has become a priority. The provision of simple, inexpensive micronutrient supplements as an adjunct to HAART may have several cellular and clinical benefits, such as a reduction in mitochondrial toxicity and oxidative stress and an improvement in immune reconstitution. We reviewed observational and trial evidence on micronutrients in HIV-positive persons receiving HAART to summarize the current literature and suggest future research priorities. A small number of observational studies have suggested that some, but not all, micronutrients may become replete after HAART initiation, and few intervention studies have found that certain micronutrients may be a beneficial adjunct to HAART. However, most of these studies had some major limitations, including a small sample size, a short duration of follow-up, a lack of adjustment for inflammatory markers, and an inadequate assessment of HIV-related outcomes. Therefore, few data are available to determine whether HAART ameliorates micronutrient deficiencies or to recommend or refute the benefit of providing micronutrient supplements to HIV-positive persons receiving HAART. Because micronutrient supplementation may cause harm, randomized placebo-controlled trials are needed. Future research should determine whether HAART initiation restores micronutrient concentrations, independent of inflammatory markers, and whether micronutrient supplements affect HIV-related outcomes in HIV-positive persons receiving HAART.     

HAART治疗1年对HIV/AIDS患者免疫重建效果观察

目的研究高效抗反转录病毒治疗（HAART）1年,对HIV/AIDS患者免疫重建效果的影响。方法确认人免疫缺陷病毒(HIV)感染者35例,检测CD4+T淋巴细胞<350/μL,开始HAART治疗,并于治疗0、6、12个月时分别检测其病毒载量及CD4+T淋巴细胞、CD8+T淋巴细胞、CD4+童贞细胞、CD4+记忆细胞、CD8+激活细胞计数。结果治疗前,HIV RNA处于高复制水平,平均(4.62±1.09)×106copies/mL,HAART治疗6个月及12个月时均低于检测下限。患者的CD4+T淋巴细胞、CD4+童贞细胞和CD4+记忆细胞均明显增加,12个月时,各组细胞计数［分别为(312±109.22) /μL、（150±57.34）/μL、（212±48.06）/μL］与基线［分别为（183±83.73）/μL、（73±20.40）/μL、（119±30.42）/μL］比较,差异有统计学意义(P<0.01),但仍低于健康对照组 ［分别为（768±146.41）/μL、（424±87.06）/μL、（442±61.40）/μL］（P<0.05）;CD8+T淋巴细胞计数（427±99.79）/μL较基线（597±111.43）/μL明显下降（P<0.05）,但仍高于健康对照组（208±37.39）/μL（P<0.05）。结论HAART能快速抑制HIV复制,治疗1年能部分恢复HIV/AIDS患者免疫功能。     

Effect of highly active antiretroviral therapy on multiple AIDS-defining illnesses among male HIV seroconverters

The effect of highly active antiretroviral therapy (HAART) on multiple acquired immunodeficiency syndrome (AIDS)-defining illnesses remains unclear. Between 1984 and 2005, 573 male human immunodeficiency virus seroconverters in four US urban centers were followed for a median of 9.7 years. During follow-up, 345, 113, 50, and 65 men incurred 0, 1, 2, and >2 AIDS-defining illnesses, respectively. The authors extend the Cox proportional hazards model to determine whether the effect of HAART, as measured by calendar periods, persists beyond the first AIDS-defining illness. After adjustment for race and age at seroconversion, the hazards of a first through third AIDS-defining illness in the HAART calendar period (beyond July 1995) were 0.31 (95% confidence interval (CI): 0.21, 0.46), 0.39 (95% CI: 0.22, 0.74), and 0.33 (95% CI: 0.14, 0.79), respectively, relative to the monotherapy and combination therapy reference calendar period (January 1990-July 1995) and therefore did not attenuate with the number of prior AIDS-defining illnesses (p for homogeneity = 0.83). After the authors averaged over multiple AIDS-defining illnesses, the hazard of an AIDS-defining illness in the HAART calendar period was 0.34 (95% CI: 0.25, 0.45) relative to the reference calendar period. HAART protects against initial and subsequent AIDS-defining illnesses, whose inclusion in analysis markedly increased the precision of the estimated hazard ratio.     

高效抗逆转录病毒疗法引起线粒体毒性的研究进展

HAART是目前治疗HIV感染者/艾滋病患者最有效的治疗方法.近年的研究表明,HAART显著降低了艾滋病相关疾病的发病率和死亡率.然而,随着HAART使用的增加,其毒副作用问题日益彰显,其中线粒体毒性成为研究热点.由于国内对HAART线粒体毒性研究较少,目前我国尚无监测相关线粒体毒性的有效方法.此文对HAART导致线粒体毒性的临床表现、发病机制及实验室检测等进行了综述.     

Effects of olestra, a noncaloric fat substitute, on daily energy and fat intakes in lean men.

Nutrient and energy intakes, hunger, and fullness were examined after the replacement of 36, 20, or 0 g fat in breakfast with olestra, a noncaloric fat substitute. Twenty-four lean, nondieting men (aged 21-30 y) participated in a placebo-controlled, three-condition crossover design. Self-selected, ad libitum intakes at lunch and dinner were monitored in the laboratory. Evening snacks and breakfast the next day were assessed through food diaries. Visual-analog-scale ratings including hunger and fullness were collected throughout the test days. Single-meal olestra substitution produced a significant dose-related reduction in the amount and percentage of energy from fat consumed daily with a reciprocal increase in carbohydrate intake. Daily energy intakes were not significantly different nor did ratings of hunger and fullness vary systematically between conditions. Consumption of olestra can reduce fat intake and increase carbohydrate intake without affecting total daily energy intake or usual patterns of hunger and fullness.     

Calculating energy requirements for men with HIV/AIDS in the era of highly active antiretroviral therapy

OBJECTIVES: 1. To determine if resting energy expenditure (REE) adjusted for body composition is elevated in HIV-positive males when compared with healthy controls in the era of highly active antiretroviral therapy. 2. To examine the accuracy of prediction equations for estimating REE in people with HIV. 3. To determine if REE adjusting for body composition is significantly different between those HIV-positive subjects reporting lipodystrophy (LD) or weight loss (>or=5%) and those who are weight stable when compared to controls. DESIGN: Cross-sectional study. SETTING: Tertiary referral hospital HIV unit and an outpatient clinic specializing in HIV care. SUBJECTS: HIV-positive males (n=70) and healthy male controls (n=16). METHODS: REE was measured using indirect calorimetry. Body composition was assessed using bioelectrical impedance analysis. RESULTS: 1. REE when adjusted for fat-free mass and fat mass using the general linear model (analysis of covariance) was greater in HIV-positive subjects than controls (7258+/-810 kJ, n=70 vs 6615+/-695 kJ, n=16, P<0.05). 2. The Harris and Benedict, Schofield, Cunningham and the two equations previously published by Melchior and colleagues in HIV-positive subjects all gave an estimate of REE significantly different from the measured REE in the HIV-positive subjects, therefore a new prediction equation was developed. The inability of the published equations to predict REE in the different HIV-positive subgroups reflected the heterogeneity in body composition. 3. REE adjusted for fat-free and fat mass was significantly greater in the both the HIV patients who were weight stable and those with lipodystrophy compared with the healthy controls. CONCLUSION: REE is significantly higher in HIV-positive males when compared with healthy controls. Body composition abnormalities common in HIV render the use of standard prediction equations for estimating REE invalid. When measuring REE in HIV-positive males adjustment steps should include fat-free and fat mass.     

重庆市艾滋病抗病毒治疗病例死亡流行病学分析

目的 了解艾滋病抗病毒治疗病死率,分析治疗病例死亡流行病学特征,为开展艾滋病抗病毒治疗时机选择提供建议.方法 从全国艾滋病综合防治数据信息系统导出治疗病人基本数据库,数据库核查后导入SPSS16.0软件进行统计分析.结果 全市累计治疗死亡病例215例,死亡病例平均年龄(42.8±11.5)岁,男性占72.1％,女性占27.9％;治疗病死率为10.5％,开始治疗时CD4≤50个/μl病人病死率为28.7％,CD4在51～200个/μl病人病死率为11.7％,CD4＞ 200个/μl病人病死率为2.2％;在治疗3个月内死亡的占54.4％,12个月内死亡的占80.5％.结论 过晚抗病毒治疗不利于减少艾滋病死亡,建议加强对感染者早期治疗的宣传.     

Association of lean tissue and fat mass with bone mineral content in children and adolescents.

OBJECTIVES: There has been uncertainty in the adult body composition literature about whether fat mass (FM) or fat free mass is a better predictor of bone mineral content and bone mineral density. This issue has recently also been raised in the pediatric literature. Based on suggested skeletal muscle-bone relationships, this study tested the hypothesis that in children and adolescents lean tissue mass (LTM) is a better predictor of total bone mineral content (TBMC) than is FM. RESEARCH METHODS AND PROCEDURES: Subjects were 133 Italian children and adolescents, 5 to 17 years of age, undergoing a routine medical screen. FM (kilograms), LTM (kilograms), and TBMC (kilograms) were measured by DXA. Multiple regression analyses tested the independent association of FM and LTM with bone mineral content. RESULTS: Regression analyses, adjusting for pubertal status and other covariates, showed that FM and LTM were independently associated with TBMC. These associations were similar for boys and girls. TBMC was more strongly associated with LTM than FM. DISCUSSION: These observations support the hypothesis that in children and adolescents a close association exists between LTM, a measure of skeletal muscle, and skeletal characteristics.     

河南省HIV-1感染者抗病毒治疗效果及耐药发生的研究

目的 了解河南省部分地区HIV-1感染者高效抗逆转录病毒治疗效果及耐药变异发生情况.方法 招募HIV-1感染者105例,每半年进行1次调查,利用流式细胞技术对CD4+T淋巴细胞计数,使用NASBA方法测定病毒载量,利用RT-PCR方法扩增HIV-1 pol区基因,进行基因型耐药性分析.结果 接受抗病毒治疗后HIV-1感...     

Hormonal contraceptive use and the effectiveness of highly active antiretroviral therapy

The role of hormonal contraceptive use in the effectiveness of highly active antiretroviral therapy (HAART) was examined among participants in the Women's Interagency HIV Study who were followed from HAART initiation to 2001. Propensity score selection was used to match 77 hormonal contraceptive users with 77 nonusers on age, race, and pre-HAART CD4-positive T-lymphocyte (CD4+ cell) count and viral load. The authors compared hormonal contraceptive users and nonusers with regard to the CD4+ cell count and viral load responses to HAART upon initiation. Proportional hazards analyses were used to assess the effect of hormonal contraceptive use on times to increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) and achievement of an undetectable viral load. There were no statistically significant differences in CD4+ cell counts and log viral load responses by hormone use after HAART initiation, except in log viral load at the third visit after initiation (p = 0.047). Time-dependent hormonal contraceptive use was not a statistically significant predictor of achieving increases in CD4+ cell count of 50 cells/mm(3) and 100 cells/mm(3) or an undetectable viral load (p = 0.517, p = 0.751, and p = 0.218, respectively) after HAART initiation. In conclusion, the authors did not find substantial evidence that use of hormonal contraceptives strongly affected responses to HAART.