Effects of highly active antiretroviral therapy on vaccine‐induced humoral immunity in HIV‐infected adults

Objectives

The acquisition of adequate vaccine‐induced humoral immunity is especially important in HIV‐infected individuals, who are at increased risk of infections. The aim of the study was to assess the safety of administering a complete vaccination programme to successfully treated HIV‐infected adults and to evaluate specific humoral responses and the effect of highly active antiretroviral therapy (HAART) interruption on these responses.

Methods

A placebo‐controlled, double‐blind clinical trial was designed and 26 HIV‐infected adults enrolled. Study participants were randomized to receive either a complete immunization schedule with commercial vaccines or placebo for 12 months. HAART was then discontinued for 6 months. Specific humoral responses were evaluated at baseline, at month 12 and after HAART interruption and compared between groups.

Results

There were neither local nor systemic secondary effects related to vaccination. Specific humoral responses to vaccines were adequate, but a loss of immunoglobulin G titres was observed after HAART interruption in 12 study participants.

Conclusions

HAART interruption may cause impairment of previously acquired vaccine‐induced immunity in HIV‐infected adults.     

Serum lipid profile in highly active antiretroviral therapy‐naïve HIV‐infected patients in Cameroon: a case–control study

Background

HIV status has commonly been found to affect the serum lipid profile.

Objectives

The aim of this study was to determine the effect of HIV infection on lipid metabolism; such information may be used to improve the management of HIV‐infected patients.

Methods

Samples were collected from December 2005 to May 2006 at Yaounde University Teaching Hospital, Yaounde, Cameroon. Lipid parameters were obtained using colorimetric enzyme assays, while low‐density lipoprotein cholesterol (LDLC) values were calculated using the formula of Friedewald et al. (1972) and atherogenicity index by total cholesterol (TC)/high‐density lipoprotein cholesterol (HDLC) and LDLC/HDLC ratios.

Results

HIV infection was most prevalent in subjects aged 31 to 49 years. Most of the HIV‐positive patients belonged to Centers for Disease Control and Prevention categories B (43.0%) and C (30.23%). Compared with control subjects, patients with CD4 counts<50 cells/μL had significantly lower TC (P<0.0001) and LDLC (P<0.0001) but significantly higher triglyceride (TG) values (P<0.001) and a higher atherogenicity index for TC/HDLC (P<0.01) and HDLC/LDLC (P=0.02); patients with CD4 counts of 50–199 cells/μL had significantly lower TC (P<0.001) and significantly higher TG values (P<0.001); patients with CD4 counts of 200–350 cells/μL had significantly higher TG (P=0.003) and a higher atherogenicity index for TC/HDLC (P<0.0002) and HDLC/LDLC (P=0.04); and those with CD4 counts >350 cells/μL had a higher atherogenicity index for TC/HDLC (P<0.0001) and HDLC/LDLC (P<0.001). HDLC was significantly lower in HIV‐positive patients irrespective of the CD4 cell count. Lipid parameters were also influenced by the presence of opportunistic infections (OIs).

Conclusion

HIV infection is associated with dyslipidaemia, and becomes increasingly debilitating as immunodeficiency progresses. HDLC was found to be lower than in controls in the early stages of HIV infection, while TG and the atherogenicity index increased and TC and LDLC decreased in the advanced stages of immunodeficiency.

     

182例HIV/AIDS实施高效抗反转录病毒治疗的疗效评价

目的分析182例HIV/AIDS实施高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)的效果及其影响因素,为进一步有效治疗提供依据。方法采用回顾性调查方法,对我院接受规范HAART的182例HIV/AIDS患者的CD4+T淋巴细胞绝对计数和病毒载量进行分析。结果 182例中,157例治疗后CD4+T淋巴细胞计数增加,且在治疗后前6个月内增加速度最快,随着治疗时间延长则较为缓慢。病毒载量在治疗后的6个月内下降最快,大部分降至血浆检测不到的水平,6个月后比较稳定;但随着治疗时间延长,部分患者的病毒载量出现反弹,可能与患者服药依从性差和病毒耐药性的出现有关。治疗前后CD4+T淋巴细胞计数差异有统计学意义(P0.05)。多因素logistic回归分析表明年龄和病毒载量是影响HAART疗效的危险因素,基线CD4+T淋巴细胞计数和按时服药是保护因素。结论 HAART能明显增加CD4+T淋巴细胞计数,降低病毒载量,有效控制机会感染,治疗效果显著。影响HAART疗效的因素是多方面的,在治疗过程中应综合考虑各种可能影响因素以提高疗效,对符合条件的患者应尽早进行规范的抗病毒治疗。     

Persistent low-level viraemia and virological failure in HIV-1-infected patients treated with highly active antiretroviral therapy

OBJECTIVE: To assess the prognostic significance of persistent low-level viraemia (PLV, defined as persistent plasma viral loads of 51-1000 HIV-1 RNA copies/mL for at least 3 months) in patients who had achieved viral suppression on antiretroviral therapy (ART). METHODS: A retrospective cohort of HIV-infected patients who received ART, were followed-up for > or =12 months, made regular visits to the clinic during which blood tests were performed for an ultrasensitive HIV RNA assay every 3 months, and achieved viral loads <50 copies/mL were evaluated. Virological failure was defined as two consecutive viral load measurements >1000 copies/mL. RESULTS: Of 362 patients, 78 (27.5%) experienced PLV. The demographics of patients with and without PLV were similar. PLV occurred at a mean (+/-standard deviation) of 22.6+/-16.9 months after ART initiation and lasted for 6.4+/-3.4 months. During a median follow-up of 29.5 months, patients with PLV had a higher rate of virological failure (39.7% vs 9.2%; P < 0.001). The median time to failure was 68.4 months [95% confidence interval (CI) 37.0-99.7] for patients with PLV and >72 months for patients without PLV (log rank test, P < 0.001). By Cox regression, patients with PLV had a greater risk of virological failure [hazard ratio (HR) 3.8; 95% CI 2.2-6.4; P < 0.001]. Among patients with PLV, a PLV of >400 copies/mL (HR 3.3; 95% CI 1.5-7.1; P = 0.003) and a history of ART (HR 2.4; 95% CI 1.0-5.7; P = 0.042) predicted virological failure. CONCLUSIONS: PLV is associated with virological failure. Patients with a PLV >400 copies/mL and a history of ART experience are more likely to experience virological failure. Patients with PLV should be considered for treatment optimization and interventional studies.     

Predictors of growth and body composition in HIV‐infected children beginning or changing antiretroviral therapy

Objectives

The aim of the study was to describe growth and body composition changes in HIV‐positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters.

Methods

Ninety‐seven prepubertal HIV‐positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999–2002 (NHANES) to generate z‐scores and with results for HIV‐exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters.

Results

All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height²) z‐scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z‐score decreased (P=0.045), but body mass index and per cent body fat z‐scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid‐thigh circumference and FFM z‐scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z‐scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid‐thigh muscle circumference were also associated with CD4 percentage. Case–control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time.

Conclusions

In these HIV‐positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received.     

Effects of age and sex on immunological and virological responses to initial highly active antiretroviral therapy

BACKGROUND: Highly active antiretroviral therapy (HAART) has increased longevity. Currently, women comprise >50% of HIV-infected individuals worldwide. It is not known if there are differences between the sexes in the immunological and virological responses to HAART across the age strata. METHODS: Immunological reconstitution and virological response in the first 6 months of a first HAART regimen in two observational clinical HIV-infected cohorts were compared by both sex and age (>or=50 vs. <50 years old). RESULTS: A total of 246 individuals (28% women) were included in the study; 63 cases (>or=50 years old) and 183 controls (<50 years old). Over two-thirds of patients had HIV RNA levels <400 HIV-1 RNA copies/mL and CD4 count increases >or=50 cells/microL at 6 months from therapy initiation. There were no differences in immunological reconstitution across age and sex strata (P=0.81) and no differences in virological suppression, even after adjusting for type of HAART (P=0.68) or restricting the analysis to women only (P=0.81). These results suggest that younger and older women and men may have similar short-term initial HAART outcomes. CONCLUSIONS: Further evaluation of longer term clinical response to initial HAART regimen based on sex and age is indicated, especially with more efficacious and simplified antiretroviral regimens and the associated decrease in mortality.     

Adipokine profiles and lipodystrophy in HIV‐infected children during the first 4 years on highly active antiretroviral therapy

Objective

The aim of the study was to evaluate the evolution of plasma adipokines and lipodystrophy in protease inhibitor‐naïve vertically HIV‐infected children on highly active antiretroviral therapy (HAART).

Patients and methods

We carried out a multicentre retrospective study of 27 children during 48 months on HAART. Every 3 months, CD4+ T‐cells, CD8+ T‐cells, viral load (VL), cholesterol, triglycerides, lipoproteins and adipokines were measured. Diagnoses of lipodystrophy were based on clinical examinations.

Results

We found hypercholesterolaemia (>200 mg/dL) in 9.5, 30.4, 21.7, 14.3 and 13.3% of the subjects at months 0, 12, 24, 36 and 48, respectively, and hypertriglyceridaemia (>170 mg/dL) in 14.3, 8.3, 13, 4.5 and 0% at the same time‐points. During follow‐up, and especially at the end of the study, we found an increase in plasma resistin levels and significant increases in total plasminogen activator inhibitor type 1, adiponectin, and leptin levels (P<0.05). We also observed slight increases in the leptin/adiponectin ratio, homeostatic model assessment, and C‐peptide values during the first months of treatment followed by a moderate decrease or stabilization after 24 months on HAART. At the end of the study, 12 of the 27 children (44.4%) had lipodystrophy, 10 (37%) had lipoatrophy, and 11 (40.7%) had lipohypertrophy; and only three of the 27 children (11.1%) were diagnosed with lipoatrophy and lipohypertrophy with scores ≥2.

Conclusions

HIV‐infected children showed an increase in serum adipokine levels, but this was not associated with the emergence of lipodystrophy during 48 months on HAART.     

Effect of early initiation of highly active antiretroviral therapy on CD4 cell count and HIV-RNA viral load trends within 24 months of the onset of acute retroviral syndrome

Objectives

The effect of starting highly active antiretroviral therapy (HAART) early after the onset of acute retroviral syndrome (ARS) on CD4 and HIV‐RNA trends was studied over a 2‐year follow‐up period.

Methods

Four groups of HIV‐infected patients stratified according to the time interval from ARS onset to HAART initiation and a control group of untreated patients were compared. Results The results indicated that the earlier the start of HAART, the faster was the rate of CD4 increase and HIV‐RNA decrease. However, this difference did not seem to persist at 24 months.

Conclusions

The optimal treatment strategy for HIV‐infected patients needs to be explored further.     

Efficacy and safety of pegylated interferon alpha‐2a therapy for chronic hepatitis C in HIV‐infected patients with haemophilia

Summary. The objective of this study was to evaluate the efficacy and safety of pegylated interferon (PEG‐IFN) alpha‐2a monotherapy in a cohort of Chinese haemophilic patients co‐infected with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) and undergoing highly active antiretroviral drugs therapy. Twenty‐two (n = 22) patients with CD4 lymphocyte counts over 200 cells μL^?1 were treated with 180 μg of PEG‐IFN alpha‐2a subcutaneously once in a week for 48 weeks. HCV load (HCV RNA), HIV load (HIV RNA) and CD4 lymphocyte counts were measured at baseline and 4, 12, 24, 48 and 72 weeks after initiation of anti‐HCV therapy. Efficacy and safety were analysed according to baseline CD4 status (≥350 cells μL^?1). Significant HCV‐RNA decreases (>1 log₁₀ copies mL^?1) were observed through week 72 after PEG‐INF alpha‐2a monotherapy across both CD4 strata. CD4 status was not associated with treatment outcomes as evaluated using rapid viral response rate (P = 0.655), early viral response rate (P = 0.387), end‐of‐treatment viral response rate (P = 1.000) or sustained viral response rate (SVR, P = 0.674). A sustained virological response was achieved in nine patients (41%), five with genotype 2a (83%) and four with genotype 1b (25%, P = 0.023). SVR was HCV genotype dependent. Eleven patients required a dose reduction in PEG‐IFN alpha‐2a. PEG‐IFN alpha‐2a monotherapy could be considered as a safe and effective option for the treatment of HCV infection in HIV patients with haemophilia, particularly in resource‐limited settings. While higher CD4 lymphocyte counts resulted in greater HCV‐RNA reduction, HCV genotype was a predictor for sustained virological response.