Immune restoration disease in HIV-infected individuals receiving highly active antiretroviral therapy: clinical and immunological characteristics

BACKGROUND: HIV-infected patients responding to HAART can show a diverse spectrum of symptoms caused by inflammatory reaction. The pathogenesis of this phenomenon, called immune restoration disease (IRD), is unclear. This study describes the spectrum of IRD and analyses the immunological and clinical parameters that could be related to its development. METHODS: In a retrospective, matched case-control study, 17 HIV-infected individuals who developed inflammatory symptoms < 12 months after initiation of HAART were included. HIV-infected controls were matched for age, gender and CDC classification. Factors included in the analysis were: CD4+ and CD8+ cell counts, deltaCD4+ and deltaCD8+, CD4/CD8 ratios, HIV-1-RNA load (VL), AVL and the number of CDC events prior to HAART. RESULTS: The median time after initiation of HAART and developing IRD (n = 17) was 72 days (range 2-319). In nine cases (53%) a mycobacterial infection was identified as the underlying cause. HAART was started at a mean CD4+ count (+/- SD) of 55 x 10(6) /l (+/- 59) and 85 x 10(6) /l (+/- 78.0) for cases and controls, respectively (p = 0.13). After initiation of HAART, the CD4+ count showed a 10.6 fold increase at the onset of IRD in the cases and a 2.7 fold increase in the controls in an equal period of time (p = 0.020). The other parameters analysed did not differ significantly between cases and controls. CONCLUSION: We conclude that the risk of developing IRD is associated with a high-fold increase in CD4+ lymphocytes. In this study, mycobacteria are the pathogens most frequently associated with IRD.     

Clinical and immunological benefits from highly active antiretroviral therapy in spite of limited viral load reduction in HIV type 1 infection

Both naive and memory T lymphocyte responses are lost during advanced HIV infection. Treatment with highly active antiretroviral therapy (HAART) is associated with an increase in T lymphocytes and a reduction in viral load. However, the viral response to HAART in patients with low levels of helper T lymphocytes and a high viral load is often not satisfactory. We investigated the capacity of long-term HAART to reconstitute the immune system in severely ill patients. A nonselected longitudinal patient population with high baseline viral levels and CD4(+) cells below 100 x 10(6)/liter were monitored for 2 years during HAART. Markers to estimate the therapeutic effects included viral levels and cell surface markers representing naive and memory T lymphocytes as well as activation markers, B cells, NK cells, and clinical events. After 2 years of treatment, viral load was reduced to undetectable levels in 55% (viral responders, vRs) and less than 1 log (median value) from baseline in 45% (viral low responders, vLRs). Elevated numbers of memory and naive CD4(+) and CD8(+) cells as well as a decrease in activation markers were seen in both vRs and vLRs. However, the magnitude was greater in vRs. No differences in the clinical outcome were observed between vRs and vLRs. We conclude that most patients, even in advanced stages of HIV disease, benefited from HAART. The magnitude of the response was related to good viral reduction, but even patients with poor viral reduction had a recovery of naive and memory CD4(+) and CD8(+) cells. Even a small reduction in viral load is thus of importance for health and potentially also for years of survival.     

Predictive value of adherence in patients starting highly active antiretroviral treatment for HIV infection

Strict adherence to the prescribed drug regimen is one of the most important predictors of success in the antiretroviral therapy of HIV infection. Ideally, patients should learn to optimise their drug adherence before they start antiviral therapy. This study evaluated the predictive role of adherence during the first four weeks of treatment for mid-term treatment outcome. Adherence was evaluated using electronic dosing systems during the first 25 days of therapy in 66 drug-na?ve patients starting a new antiretroviral therapy. Treatment outcome (HIV-RNA suppression) was evaluated at week 24 of treatment. Good adherence (>95%doses taken) was associated with better rates of viral suppression (77% vs. 44% Patients with HIV-RNA below 50 copies/ml). Specific education programmes targeted at the achievement of optimal adherence during the first few weeks of therapy might result in better treatment results.     

One-year adherence to clinic visits after highly active antiretroviral therapy: a predictor of clinical progress in HIV patients

OBJECTIVE: To determine whether adherence to clinic visits early after initiation of highly active antiretroviral therapy (HAART) is predictive of long-term clinical outcome. DESIGN: Observational cohort study. SETTING: A tertiary referral hospital. SUBJECTS: A total of 387 adult HIV patients who were followed for at least 1 year after initiation of HAART between January 1998 and December 2004. MAIN OUTCOME MEASUREMENTS: The effect of 1-year adherence to clinic visits on the occurrence of new AIDS-defining illness or death was assessed using Kaplan-Meier survival estimates, and hazard ratios were estimated using Cox proportional hazards regression model. RESULTS: Multivariate analysis revealed that advanced clinical stage, fewer new drugs in HAART, and longer total elapsed time without clinical visits for 1 year after HAART were all significant risk factors for the occurrence of new AIDS-defining illnesses or death. Compared with no missed visits, the hazard ratio adjusted by clinical stage and number of new drugs in HAART was 2.87 (95% confidence interval [CI], 1.34-6.16, P = 0.007) for one missed appointment, 4.37 (95% CI: 1.74-10.98, P = 0.002) for two, and 8.19 (95% CI: 2.95-22.78, P < 0.001) for three or more. CONCLUSION: Adherence to clinic visits early after initiation of HAART is an independent predictor for long-term clinical progression in HIV patients.     

Rapid efficacy of highly active antiretroviral therapy in a case of HIV myelitis

An HIV-seropositive patient with severe immunodepression was diagnosed as having HIV myelitis. Plasma and cerebrospinal fluid (CSF) HIV-RNA PCR were, respectively, 4.11 and 5.19log(10). After 1 month of treatment with highly active antiretroviral therapy (HAART), there was clinical recovery and both plasma and CSF HIV viral load had decreased considerably. This dramatic improvement was associated with a high concentration of antiviral drugs in the CSF, suggestive of the direct efficacy of HAART on HIV myelitis.     

HIV/HBV co-infection and rate of antiretroviral treatment change after highly active antiretroviral treatment initiation in a cohort of HIV-infected patients in Greece

The current study investigated the impact of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection on the rate of change of antiretroviral drugs after the initiation of highly active antiretroviral treatment (HAART). The data on 1425 HIV-positive patients with recorded serology for hepatitis B surface antigen (HBsAg) were retrospectively analysed. The estimated rate of treatment change was slightly higher in the HBsAg-positive group (0.57 per year) compared with the HBsAg-negative group (0.50 per year). Although this difference was insignificant in multivariable modelling, the confidence intervals of the estimates barely included unity. Antiretroviral drug family, calendar period, prior exposure to antiretrovirals and the diagnosis of acquired immunodeficiency syndrome were independently associated with the number of drug alterations. A slight impact of co-infection on the frequency of treatment change after the beginning of HAART cannot be excluded. However, the paucity of studies on this issue necessitates the conduct of further research.     

Pegylated liposomal doxorubicin plus highly active antiretroviral therapy versus highly active antiretroviral therapy alone in HIV patients with Kaposi's sarcoma

Twenty-eight HIV patients either naive or failing highly active antiretroviral therapy (HAART)with moderate-advanced Kaposi's sarcoma (KS)were randomly chosen to initiate a new HAART regimen plus pegylated liposomal doxorubicin(PLD) or the new HAART regimen alone. After 48 weeks, better response rates were observed in the HAART plus PLD group (76% versus 20%).In HIV-infected patients with moderate-advanced KS, HAART alone may not be enough for KS response.     

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.     

Bilateral blindness after starting highly active antiretroviral treatment in a patient with HIV infection and cryptococcal meningitis

A 26-year-old HIV-seropositive Caucasian man with cryptococcal meningitis developed permanent bilateral blindness shortly after starting highly active antiretroviral treatment. The blindness may have been a consequence of an immune reactivation inflammatory syndrome caused by this treatment.     

HAART后艾滋病病人脂肪肝临床特点分析

目的为提高艾滋病(AIDS)病人高效抗反转录病毒治疗(HAART)后合并非酒精性脂肪肝(NAFLD)的确诊率,对艾滋病病毒(HIV)感染者/AIDS病人(简称HIV/AIDS病人)HAART后出现的高脂血症、NAFLD的临床特征进行横断面研究,初步探讨艾滋病病人HAART后合并非酒精性脂肪肝的临床和流行病学特征。方法以HAART后高脂血症作为切入点,分析HAART后高脂血症病人的体重指数(BMI)、血压、HIV感染时间、HAART治疗的药物和治疗时间、CD4细胞水平、空腹血糖、血脂水平、肝肾功能,完善腹腔彩超检查,通过影像学发现艾滋病病人中脂肪肝的变化。对有或无脂肪肝病人的上述指标进行比较。结果从2004年开始免费抗病毒治疗的300例病人中,筛查出42例HIV/AIDS病人,其中28例(66.7%)为NAFLD组,14例(33.3%)为非脂肪肝组。NAFLD组病人体重指数(23.61±2.55)kg/m2、空腹血糖(6.98±2.34)mmol/L、丙氨酸转氨酶(ALT)为(47.95±25.4)U/L;非脂肪肝组体重指数(22.06±1.96)kg/m2、空腹血糖(5.86±0.70)mmol/L,ALT为(25.22±6.75)U/L,两组比较差异有统计学意义。结论 NAFLD是HAART治疗后HIV/AIDS病人中常见的并发症,高脂血症、体重指数和高血糖与NAFLD的发生具有相关性;ALT升高是HIV/AIDS病人并发NAFLD的结果;HAART治疗的方案和治疗时间与NAFLD的发生无关。     

Two decades of HIV infection in a cohort of haemophilic individuals: clinical outcomes and response to highly active antiretroviral therapy

OBJECTIVES: Many haemophilic individuals infected with HIV died before receiving antiretroviral therapy (ART). Most who remain alive are chronically infected with hepatitis C virus (HCV), which has implications for their prognosis and choice of ART. The clinical status of a cohort of HIV-positive haemophilic men is reported together with their response to highly active antiretroviral therapy (HAART). DESIGN: Longitudinal cohort study. SETTING: A comprehensive care haemophilia centre. PATIENTS: A group of 111 haemophilic men who seroconverted to HIV in the period 1979 to 1985. RESULTS: The cohort has been followed since 1979. By 30 April 1999, 57 of the 111 men had developed AIDS and 65 had died: Kaplan-Meier rates of 57.0% [95% confidence interval (CI) 46.9-67.0) and 65.1% (95% CI 52.7-77.4) by 19.5 years, respectively. AIDS rates have declined since 1997 but death rates have remained high, largely owing to deaths from non-HIV-related causes. Thirty-five patients remain alive and under follow-up at the clinic. The 28 men who had received ART had lower CD4 cell counts than the seven patients who had not received ART, but the two groups were otherwise similar. In total, 21 patients are known to have started HAART while under care at the centre. By 10-12 months after starting HAART, viral loads dropped by 2.06 log10 copies/ml and CD4 cell counts increased by 60 x 10(6) cells/l. In 10 out of 18 patients with viral loads initially > 400 copies/ml, a viral load below this level was attained; four had changed therapy at the time. CONCLUSIONS: While the decision to initiate HAART in haemophilic men should be made carefully because of the possible adverse events, our results suggest that a good response rate was achieved in this group of men.     

Initial virological and immunologic response to highly active antiretroviral therapy predicts long-term clinical outcome.

Little is known about the long-term clinical outcomes for human immunodeficiency virus (HIV)-infected patients who have received highly active antiretroviral therapy (HAART). Determining factors associated with long-term clinical outcomes early in the course of treatment may allow modifications to be made for patients who are at a greater risk of treatment failure. To evaluate these factors, we studied 213 HIV-infected patients who had received HAART for at least 115 weeks. In the univariate analysis, virological response, which was measured as the change in virus load from baseline at month 3 of treatment, was the single best predictor of clinical outcome (relative hazard, 0.722; P=.001), independent of virological suppression. In the multivariate analysis, virological response and immunologic response, which was measured as an increase in CD4 cell count of >200 cells/mm(3), resulted in better prediction of clinical outcomes than did use of either variable alone (P=.02). Our results indicate that changes in virus load and immunologic response together are good predictors of clinical outcome and can be assessed after the initiation of HAART, which would allow clinicians to identify patients early in the course of therapy who are at greater risk of negative outcome.