The changing pattern of AIDS-defining illnesses with the introduction of highly active antiretroviral therapy (HAART)in a London clinic

OBJECTIVES: To quantify the progressive impact of combination antiretroviral therapy (ART) on the incidence of AIDS-defining illnesses (ADIs) over a 9-year period. METHODS: Retrospective cohort study. Eligible patients were 1538 AIDS-free, HIV-1-positive patients attending a large HIV clinic in west London who were at risk of developing AIDS because their CD4 count had declined to < or =350 x 10(6)/l cells during the period 1 January 1990 and 31 December 1998. Incidence rates for the 12 most frequent ADIs were compared for two time periods, 1990-1995 (pre-HAART) and 1996-1998 (post-HAART), using Poisson regression methods. Multivariate Poisson regression models were used to examine the contribution of ART and HAART to any observed temporal trends in incidence rates. RESULTS: After a median follow-up of 35 months, 450 (29%) patients had developed AIDS. Between the two time periods there was a significant decrease in the incidence of Pneumocystis carinii pneumonia (PCP) by 35% (4.11 per 100 person-years in 1990-1995 vs. 2.67 in 1996-1998;P= 0.007), Kaposi's sarcoma by 34% (3.27 vs. 2.17;P= 0.022) and cryptosporidiosis by 60% (0.76 vs. 0.31;P= 0.029). A non-significant reduction in incidence was observed for cryptococcosis by 45% (0.81 vs. 0.45;P= 0.11), oesophageal candidiasis by 29% (3.34 vs. 2.39;P= 0.053) and mycobacterium avium complex by 18% (1.58 vs. 1.29;P= 0.4), and a non-significant increase was observed for tuberculosis by 17% (0.62 vs. 0.73;P= 0.66) and non-Hodgkins lymphoma (NHL) by 51% (0.43 vs. 0.65;P= 0.31). The incidence of cerebral toxoplasmosis, cytomegalovirus, recurrent bacterial chest infections and dementia remained stable. There was a clear stepwise reduction in the incidence of PCP, Kaposi's sarcoma and cryptosporidiosis with the use of non-H AART and HAART regimens relative to no ART. In a multivariate analysis, the use of ART and HAART explained the progressive decrease in incidence of PCP and Kaposi's sarcoma. CONCLUSIONS: The incidence of most ADIs has decreased over the last 9 years. The striking reduction in the inci-dence of PCP and Kaposi's sarcoma since 1996 can be attributed to the use of combination ART and particularly HAART. The non-significant increase in the incidence of NHL and tuberculosis needs confirmation in other patient cohorts.     

Toxoplasmic encephalitis in an AIDS cohort at Puerto Rico before and after highly active antiretroviral therapy (HAART)

Highly active antiretroviral therapy (HAART) significantly reduced the toxoplasmic encephalitis (TE) incidence in acquired immunodeficiency syndrome (AIDS) patients. The TE incidence and mortality were evaluated in an AIDS cohort followed in Puerto Rico before, during, and after HAART implementation in the Island. Of the 2,431 AIDS studied patients 10.9% had TE diagnosis, with an incidence density that decreased from 5.9/100 person-years to 1.1/100 person-years after HAART. Cox proportional hazard analysis showed substantial mortality reduction among TE cases who received HAART. No mortality reduction was seen in those cases who received TE prophylaxis. Although this study shows a TE incidence and mortality reduction in the AIDS cohort after HAART, the incidence was higher than those reported in the United States AIDS patients. Poor TE prophylaxis compliance might explain the lack of impact of this intervention. Strengthening the diagnostic and opportune TE diagnosis and prompt initiation of HAART in susceptible patients is important to control this opportunistic infection.     

Mycobacterium xenopi osteomyelitis in a patient on highly active antiretroviral therapy (HAART)

Skeletal infections with atypical mycobacteria are a manifestation of advanced HIV disease, most patients having CD4 counts of less than 100 cells/mm(3). We report a case of Mycobacterium xenopi vertebral osteomyelitis in a patient on HAART with a CD4 count of 490 cells/mm(3) and viral load below the level of detection at the time of diagnosis.     

Healthcare use by varied highly active antiretroviral therapy (HAART) strata: HAART use, discontinuation, and naivety

OBJECTIVES: Prior reports have found a temporal association between the introduction of highly active antiretroviral therapy (HAART) and population rates of health service use among persons living with HIV. Our objective was to explore further the effect of HAART by comparing healthcare use among persons who use HAART and persons who discontinue HAART to that among HAART-naive and HIV-negative persons. METHODS: Longitudinal analyses of 1485 women with and at-risk for HIV who contributed data to the Women's Interagency HIV Study between April 1997 and March 2000. RESULTS: Compared with HAART-naive women, those using HAART had a higher probability of more than three primary care visits per 6 months [odds ratio (OR), 1.38; 95% confidence interval (CI), 1.16-1.65), a lower probability of more than one emergency room visit per 6 months (OR, 0.75; CI, 0.59-0.95), and a lower probability of more than one hospitalization per 6 months (OR, 0.67; CI, 0.51-0.88). Compared with HAART-naive women, women who had discontinued HAART had a higher frequency of primary care visits (OR, 1.57; CI, 1.26-1.97) but did not demonstrate a significant change in emergency room or hospital use. Modeling of a standardized population HIV-positive women without AIDS indicated hospitalization and emergency room use among HAART users was equivalent to that among HIV-negative women. CONCLUSIONS: HIV-positive HAART users (without AIDS) exhibited emergency room and hospitalization use patterns equivalent to those of HIV-negative women. Furthermore, the discontinuation of HAART was associated with a loss of the reduction in hospital use that was achieved with HAART.     

Incidence and determinants of new AIDS-defining illnesses after HAART initiation in a Senegalese cohort

Background  

Although a dramatic decrease in AIDS progression has been observed after Highly Active Anti Retroviral Therapy (HAART) in both low- and high-resource settings, few data support that fact in low-resource settings.     

Effect of highly active antiretroviral therapy (HAART) on hypergammaglobulinemia in HIV infected patients

To investigate the mechanism of hypergammaglobulinemia in HIV infected patients, the effect of highly active antiretroviral therapy (HAART) on the hypergammaglobulinemia was analyzed. Involved in this study were 34 untreated, 21 HAART-effective (complete response) and 14 HAART-non-effective (partial response) patients. Serum levels of HIV-RNA and gammaglobulin and immunoglobulin (Ig) isotypes were measured. Mean HIV-RNA levels of untreated and partial response patients were 1.6 x 10(4) copies/ml and 0.4 x 10(4) copies/ml, respectively. HIV-RNA levels of all complete response patients were below 4.0 x 10(2) copies/ml. Mean gammaglobulin percentages of untreated, partial response and complete response patients were 24.4%, 21.8% and 17.9%, respectively (p < 0.01 in untreated vs complete response patients). Mean IgG levels in the three groups were 2,489 mg/dl, 1,947 mg/dl and 1,618 mg/dl, respectively (p < 0.001 in untreated vs complete response patients). IgA levels were high in some untreated patients and lower in complete response patients. IgE levels were increased in some untreated and partial response patients, but there was no significant difference among the three groups. These results suggested that the hypergammaglobulinemia found in HIV infected patients was associated with HIV replication. The activation mechanism might differ by Ig isotypes.     

高效抗反转录病毒治疗相关性脂肪代谢综合征

自1996年高效抗反转录病毒治疗(HAART)应用于临床以来,艾滋病的发病率和死亡率已经大大降低。但HAART治疗需长期或终身服药,因此,药物的毒副作用容易导致患者的依从性下降。其中脂肪代谢综合征就是HAART用药过程中的一个比较常见的远期不良反应之一。HAART药物中与脂肪代谢有关的主要是蛋白酶抑制剂(PIs)和核苷类逆转录酶抑制剂(NRTIs),可以引起各种代谢异常和内分泌紊乱综合征。其具体的发病机制目前尚不清楚。本文就脂肪代谢综合征的发病机制、检测及治疗进行了阐述。     

Revelations of HIV-infected patients treated with highly active antiretroviral therapy (HAART) in rural Uganda

The purpose of this qualitative study was to explore the psychosocial changes revealed by persons living with HIV/AIDS (PLWHA) in western Uganda as a result of the introduction of highly active antiretroviral therapy (HAART). Fourteen participants were interviewed on two occasions. Two focus groups discussions were also conducted. Patients experienced important personal benefits as a result of HAART and the resulting clinical improvement. These benefits included a restoration of hope, self-esteem and personal agency. Patients were also relieved of the great fear which they had about the conditions of their death. The financial and social struggles introduced by AIDS illness continued after the introduction of HAART. The conclusion is that the HAART programs should provide more holistic care to patients to address the persistent family issues identified in this study.     

HIV related and non-HIV related mortality before and after the introduction of highly active antiretroviral therapy (HAART) in Norway compared to the general population

The objective of the study was to compare the mortality in HIV infected individuals to the general population, and to explore the relative contribution of HIV to mortality before and after the introduction of highly active antiretroviral therapy (HAART). All HIV patients attending Ullev?l University Hospital, Oslo, Norway before (cohort 1) and after (cohort 2) the introduction of HAART were included. Causes of deaths were classified as HIV related or not. Mortality in the Norwegian general population was standardized according to the distribution of age and gender in our cohorts. Ratios between mortality in our cohorts and the standardized mortality were calculated. The risk ratio (RR) for 5-y mortality compared to the general population was 22.6 (95% confidence interval (CI), 19.5-26.4) in cohort 1 (n = 782), and 3.96 (95% CI 2.25-6.97) in cohort 2 (n = 398). The non-HIV related mortality RR was 4.42 (95% CI 3.18-6.13) in cohort1 and 0.89 (95% CI 0.29-2.76) in cohort 2. Higher age and low CD4 cell count were associated with increased mortality. Thus, in the HAART era the mortality in HIV patients was reduced by 80%. However, the mortality in the HAART era was still 4 times higher than in the general population.     

Considering childbearing in the age of highly active antiretroviral therapy (HAART): Views of HIV-positive couples

Objectives: Based on a qualitative study conducted in Bulawayo, Zimbabwe, this article examines how the availability of HAART since April 2004 may impact the views and choices of HIV-positive couples on childbearing. Methods: In-depth interviews were conducted with 15 couples where at least one partner was HIV positive. All respondents were of reproductive age and had or were confronting reproductive and sexual decision-making. Results: HAART seems to have had a profound impact on the subject of childbearing among those who still desire to have children. Where hitherto individuals had only a desire for a child many are now, as a result of the availability of HAART, actively planning to have one. HAART has not only transformed their physical state but it has also transformed mostly what had been desire into intention. The impact, however, has not been uniform. Some respondents still desired to have a child but were not yet convinced about the efficacy of HAART in preventing vertical transmission. Some respondents felt that HAART may have a negative impact on the foetus and as such were against childbearing by HIV-positive people. No respondent indicated that their desire or intention to have a child had been extinguished by the advent of HAART. Conclusion: Based on the findings of the study, HAART seems to have had a differential but nonetheless significant role in the reproductive plans of HIV-positive couples. The study also notes that there is a need to make available complete and unbiased information on HAART, mother-to-child transmission risk (MTCT) and pregnancy to HIV-positive couples so as to enable them to make informed decisions.     

Incidence and associated factors of pulmonary tuberculosis in HIV-infected children after highly active antiretroviral therapy (HAART) in China: a retrospective study

China is a country with high tuberculosis (TB) incidence but relatively low HIV prevalence. However, due to difficulties in diagnosis and reporting, true burden of HIV-associated TB in children is unknown. The objective of this study was to describe the incidence of pulmonary TB (PTB) after antiretroviral therapy (ART) and to study risk factors. A retrospective study was performed based on routinely collected data from China national pediatric free antiretroviral treatment database. A total of 3365 children under 15 years on ART from July 2005 to October 2012 were included. Multivariable logistic regression was used to detect associated factors. Two thousand nine hundred and ninety (89%) children got infected from HIV-positive mother, with median age of 6.7 (4.1, 10.0) years at highly active antiretroviral therapy (HAART) initiation in this program. Seventy-seven (2.3%) children were diagnosed with PTB after ART during 7.3 years cohort observation. Median time of occurrence was 212 (30–514) days. Overall incidence was 0.83 (0.65–1.01)/100 person-years (py), with the peak of 3.6/100 py in the first 3 months after antiretroviral treatment. WHO stage IV at baseline showed 2 (95% CI 1.0–6.8) times more risk for developing TB. Late clinical stage at ART initiation was shown to relate with TB incidence. PTB coinfection leads to higher mortality. Early diagnosis and treatment of HIV are highly required to reduce HIV-associated morbidity and mortality due to TB.     

Thyroid function in human immunodeficiency virus patients treated with highly active antiretroviral therapy (HAART): a longitudinal study

Objective Given that few and controversial data have been reported on thyroid function in human immunodeficiency virus (HIV) patients on highly active antiretroviral therapy (HAART), we further investigated whether HAART affects thyroid hormones. Design and patients Two hundred two consecutive adult HIV patients in stable clinical condition were enrolled, 182 on HAART and 20 naïve; 128 were rechecked during follow‐up. Body mass index (BMI), CD4 cell count, HIV RNA, hepatitis C and B virus status and infection duration were determined in all HIV patients and HAART duration in treated patients. In all patients and in 60 controls, the following were measured: FT4 and FT3 by radioimmunoassay; TSH, antithyroid peroxidase (TPO) and antithyroglobulin (TG) antibodies by immunoradiometric assay. Results Abnormalities in thyroid function tests were found in 23/182 (12·6%) HAART patients, but not in naïve patients. Most abnormalities were subclinical hypothyroidism, with mean FT4 and TSH levels lower and higher, respectively, in HAART patients compared to naïve patients and controls, FT4 levels being significantly lower than controls. TSH negatively correlated with CD4 count nadir and positively with HAART duration. During follow‐up, FT4 and FT3 significantly decreased and TSH increased in patients continuing HAART, whereas CD4 counts were unmodified; subclinical hypothyroid conditions persisted and further cases occurred, whereas the only hypothyroid patient who interrupted HAART shows a normalization of thyroid tests. Patients on stavudine, included in most hypothyroid patient protocols, had significantly lower FT4 levels with prolonged treatment. Conclusions HAART, particularly stavudine, is associated with a high prevalence of subclinical hypothyroidism. Hypotheses are made regarding responsible mechanisms and risk factors. Thyroid function should be tested and sequentially rechecked in HAART patients.     

HAART对HIV感染者/AIDS病人短期生活质量影响研究

目的 探讨艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人接受抗病毒治疗6个月时,生活质量有无变化.方法 给予安徽省两地40名HIV感染者/AIDS病人高效抗逆转录病毒治疗(HAART),应用病历报告表的形式收集参加治疗病人的人口学信息、流行病学、临床及实验室检查信息,同时采用MOS-HIV量表,对病人治疗前和治疗6个月时生活质量进行调查,对相关数据进行统计分析.结果 40名HIV感染者/AIDS病人平均年龄(42.2±8.8)岁(26～62岁),治疗前CD4平均为(197±41)个/μl(94～271),治疗6个月时体重平均增加(5.1±4.5)kg(t＝7.24,P＜0.01),CD4平均增加(122±109)个/μl(t＝7.07,P＜0.01).采用MOS-HIV量表评定,病人躯体状况及精神状况在治疗后均有显著改善;维度分析显示,在健康感知、认知功能、疼痛、精神健康、精力与劳累、健康压力、生活状况、健康的变化方面,治疗前后的差异有显著的统计学意义(P＜0.01).结论 抗病毒治疗6个月时病人CD4细胞计数明显升高、体重增加、生活质量改善,躯体及精神状况均有所提高.     

Inpatient care of the HIV infected patient in the highly active antiretroviral therapy (HAART) era

The inpatient presentation of the HIV infected patient has changed over the years. From the early years when patients presented with accumulating opportunistic infections that led to an early demise to the HAART era with reports of dramatic decreases in opportunistic infections and improvements in life expectancy, the evolution of inpatient HIV care has been a challenge to the clinician. In the HAART era the presentation of the HIV inpatient has diversified and in many ways is more challenging than the management of the HIV inpatient in the pre-HAART era. We will discuss the changing dynamics of HIV inpatient care from socioeconomic changes to changes in the presentation and reasons for hospitalization.     

Reactive hemophagocytosis associated with the initiation of highly active antiretroviral therapy (HAART) in a patient with AIDS

Reactive hemophagocytosis has been associated with neoplasia, bacteria, parasitic, and viral infections including human immunodeficiency virus (HIV). Here we present a case of reactive hemophagocytosis associated with the initiation of highly active antiretroviral therapy (HAART), probably representing a syndrome termed the immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution syndrome.