Effect of GB virus C co-infection on response to generic HAART in African patients with HIV-1 clade C infection

In 38 African AIDS patients initiating generic HAART, GB virus C (GBV-C) RNA-positive patients retained GBV-C viraemia during 52 weeks of HAART, had a faster decline in HIV viral load (P = 0.03), fewer opportunistic infections (14.3 versus 50%, P = 0.18), and suffered no serious adverse events (none versus 61%, P = 0.008) compared with patients without GBV-C. GBV-C co-infection may be associated with a beneficial effect on African AIDS patients treated with generic HAART.     

Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients

To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.     

Early and late effects of highly active antiretroviral therapy: a 2 year follow-up of antiviral-treated and antiviral-naive chronically HIV-infected patients

BACKGROUND: Control of HIV replication can be observed in highly active antiretroviral therapy (HAART)-treated and, occasionally, in HAART-naive patients. The immunological correlates of these situations were examined in a longitudinal study. DESIGN: A prospective study. Immunovirological analyses in 16 chronically HIV-infected, HAART-naive patients (time 0) who started HAART. Fifteen patients (short-term HAART) were re-evaluated after 24 months (time 1). Results were compared with those of 30 patients who received HAART for more than 12 months before the study period (long-term HAART) and were analysed at the same timepoints. Fifteen patients who were antiviral therapy naive (naive) at both timepoints were also studied. RESULTS: Over a 24-month period CD4 and CD8 cell counts and viraemia remained unchanged in naive and long-term HAART patients; CD4 cell counts increased and viraemia diminished in short-term HAART individuals. Antigen-stimulated proliferation was unmodified in naive and short-term HAART patients, but improved in long-term HAART individuals. Gp160-stimulated IL-2 and IFN-gamma production was augmented in long-term HAART patients and marginally modified in other patients. IL-7 production was unmodified in naive individuals, augmented in short-term HAART patients, and diminished in long-term HAART patients. Chemokine production was similar in all patients. Naive patients showed the highest CD8 cell counts at both timepoints. CONCLUSION: HAART has a major impact on the outcome of HIV infection, even if functional immune modulation in HAART-treated patients is evident only after long periods of therapy. Low but detectable HIV replication in HAART-naive patients with preserved immune functions might not be associated with CD4 cell reduction, functional immune defects, or changes in viraemia.     

HIV infection in the elderly

The prevalence of HIV in patients over the age of 50 years is increasing. Although older patients may achieve equal or better virologic suppression at equal rates compared with younger patients, the immunologic benefit of highly active antiretroviral therapy (HAART) in older patients may be reduced compared with younger patients. Comorbidities are more common in older patients than younger patients and can impact management of HIV in these patients. Providers must be cognizant of drug-drug interactions and side effects of HAART regimens when selecting an antiretroviral regimen in older HIV patients. As the HIV-infected population ages, there is a growing need to better determine the ideal HAART regimen and timing of HAART initiation in older patients.     

Does transient HAART during primary HIV-1 infection lower the virological set-point?

OBJECTIVES: To assess the influence of patient characteristics, treatment precocity (how early) and duration of sustained virological response to highly active antiretroviral therapy (HAART) on HIV RNA levels after withdrawal of treatment started during primary infection and to compare HIV RNA levels after HAART withdrawal with levels reached at the same time point during the natural history of infection in the pre-HAART era. DESIGN: HIV RNA was analysed using linear mixed-effects models for 58 patients from the PRIMO cohort (1996-2003) treated during primary infection (with sustained virological responses until HAART interruption) and 116 untreated patients enrolled in the SEROCO cohort within 6 months following infection (1988-1995). Viral loads were estimated in PRIMO patients 36 months after infection (12 months after treatment interruption) and were estimated for the SEROCO patients 36 months after infection, after adjustment for gender and age. RESULTS: HIV RNA levels 12 months after HAART interruption were independently associated with levels at HAART initiation and with the CD4 cell count at HAART interruption, but not with the precocity of HAART or the duration of virological response to HAART. Thirty-six months after infection, mean HIV RNA levels were 3.95 log10 copies/ml 12 months after stopping HAART and 4.11 log10 copies/ml in never-treated patients. CONCLUSION: Viral load 12 months after withdrawal of transient effective HAART started during primary infection is similar to viral load at the same time after infection in never-treated patients, suggesting that early HAART initiation does not lower the virological set-point.     

HIV infection and high-density lipoprotein: the effect of the disease vs the effect of treatment

HIV infection is commonly associated with hypoalphalipoproteinemia. It is not clear how much the HIV infection and/or treatment contribute to the changes in high-density lipoprotein (HDL) levels. Blood lipids of HIV-positive males were assessed in a retrospective study. The following groups of patients were studied: (1) untreated for at least 6 months; (2) treatment with highly active antiretroviral therapy (HAART) without protease inhibitor (PI); (3) treatment with a HAART regimen that includes a PI (HAART/PI); (4) treatment with HAART that includes low-dose ritonavir and a PI (HAART/PI/boost). Lipoprotein levels were compared with those of age-matched HIV-negative healthy subjects. Compared with the control group, HDL-cholesterol (HDL-C) levels were 22%, 11%, 14%, and 11% lower for currently untreated HIV, HAART, HAART/PI, and HAART/PI/boost groups, respectively. Negative correlations were found among HDL-C level, peak and current viral load, and duration of the disease and the treatment. A positive correlation was found between HDL-C and current and nadir CD4 cell count and CD4 percentage. When patients were divided into subgroups based on duration of antiretroviral therapy, patients treated with HAART and HAART/PI for 3 to 6 years were significantly less likely to have high HDL-C levels compared with the control group and patients treated for 1 to 3 years. A 5-fold decrease in the proportion of subjects with high HDL-C and a 3-fold increase in those with low HDL-C were found in the group treated with HAART/PI/boost. These data suggest that hypoalphalipoproteinemia in patients with HIV is likely to be secondary to HIV infection itself.     

Morbidity and mortality in ageing HIV‐infected haemophilia patients

Over 25 years of follow‐up is now available for HIV‐infected haemophilia patients. The aim of this study was to retrospectively asses the morbidity and mortality of HIV infection and the effects of HAART in these patients. Data on HIV infection, its treatment and all types of comorbidity were collected from medical records of all 60 HIV‐positive haemophilia patients who were treated at the Van Creveldkliniek since 1980 and compared with data from 152 HIV‐negative patients with severe haemophilia and the general age‐matched male population. AIDS developed in 27 patients (45%), while 31 patients died (52%). Death was solely or partially AIDS‐related in 71%. Development of AIDS and AIDS‐related deaths declined strongly after the introduction of HAART. Only one major ischaemic cardiovascular event occurred in our study population. Of the 27 patients who were still treated at our clinic in 2010, 25 (93%) were on HAART. They had more often hypertension and diabetes, but less often overweight and obesity and lower cholesterol levels than the general population. The occurrence of spontaneous intracranial bleeding was higher in HIV‐positive haemophilia patients on HAART than in HIV‐negative patients with severe haemophilia (16.6 vs. 1.2 per 1000 patient years). Since the introduction of HAART, the impact of HIV infection on morbidity and survival has decreased. The increased prevalences of hypertension and diabetes, however, warrant regular screening. HIV‐positive haemophilia patients on HAART appear to have an increased risk of spontaneous intracranial bleeding.     

Trends of mortality and causes of death among HIV-infected patients in Taiwan, 1984-2005

Background

The aim of this study was to analyse the trends of mortality and causes of death among HIV‐infected patients in Taiwan from 1984 to 2005.

Methods

Registered data and death certificates for HIV‐infected patients from Taiwan Centers for Disease Control were reviewed. Mortality rate and causes of deaths were compared among patients whose HIV diagnosis was made in three different study periods: before the introduction of highly active antiretroviral therapy (HAART) (pre‐HAART: from 1 January 1984 to 31 March 1997), in the early HAART period (from 1 April 1997 to 31 December 2001), and in the late HAART period (from 1 January 2002 to 31 December 2005). A subgroup of 1161 HIV‐infected patients (11.4%) followed at a university hospital were analysed to investigate the trends of and risk factors for mortality.

Results

For 10 162 HIV‐infected patients with a mean follow‐up of 1.97 years, the mortality rate of HIV‐infected patients declined from 10.2 deaths per 100 person‐years (PY) in the pre‐HAART period to 6.5 deaths and 3.7 deaths per 100 PY in the early and late HAART periods, respectively (P<0.0001). For the 1161 patients followed at a university hospital (66.8% with CD4 count <200 cells/μL), HAART reduced mortality by 89% in multivariate analysis, and the adjusted hazard ratio for death was 0.28 (95% confidence interval 0.24, 0.33) in patients enrolled in the late HAART period compared with those in the pre‐HAART period. Seventy‐six per cent of the deaths in the pre‐HAART period were attributable to AIDS‐defining conditions, compared with 36% in the late HAART period (P<0.0001). The leading causes of non‐AIDS‐related deaths were sepsis (14.7%) and accidental death (8.3%), both of which increased significantly throughout the three study periods. Compared with patients acquiring HIV infection through sexual contact, injecting drug users were more likely to die from non‐AIDS‐related causes.

Conclusions

The mortality of HIV‐infected patients declined significantly after the introduction of HAART in Taiwan. In the HAART era, AIDS‐related deaths decreased significantly while deaths from non‐AIDS‐related conditions increased.     

Thrombotic thrombocytopaenic purpura in HIV-infected patients

Thrombotic thrombocytopaenic purpura (TTP) results from deficiency of von Willebrand factor-cleaving protease (vWF-cp) activity. Eight HIV-infected patients presented with TTP, representing 12.5% of all TTP treated at this centre. In four patients presentation with TTP revealed underlying HIV infection, the other four patients were previously known to be HIV infected, with plasma exchange and highly active antiretroviral therapy (HAART) all recovered. Normalization of vWF-cp activity was associated with recovery. Relapse occurred in two patients who discontinued HAART against medical advice, suggesting that HIV has a causal role in this condition. Given the clear benefit from HAART in addition to plasma exchange, these data suggest that all patients presenting with TTP should undergo HIV testing.     

Predictors of CD4+ cell count response and of adverse outcome among HIV-infected patients receiving highly active antiretroviral therapy in a public hospital in Peru.

OBJECTIVES: Our aim was to investigate CD4+ cell recovery and adverse outcome after highly active antiretroviral therapy (HAART) under the Peruvian National Program for HIV. METHODS: A prospective, observational study was conducted between May 2004 and September 2005. Data were collected from records of patients receiving HAART at a public hospital under the Peruvian National Program for HIV. Predictors of CD4+ cell count recovery and adverse outcome were analyzed by multiple regression. RESULTS: Three hundred and twenty-six patients were included in the study. The mean increase in CD4+ cell count at six months was 114 cells/microl (95% confidence interval: 103-126). Patients with a lower CD4+ cell count at baseline and those starting HAART with a didanosine-based regimen had a higher increase in CD4+ cell count at six months. Patients starting HAART with a stavudine-based regimen had a lower increase in CD4+ cell count at six months. World Health Organization clinical stage IV at diagnosis of HIV infection, a low body weight at baseline, and starting HAART with a stavudine-based regimen were independently associated with an adverse outcome. CONCLUSIONS: The CD4+ cell response to HAART under Peruvian National Program for HIV was comparable with reports from other countries. However, the fact that advanced clinical disease predicted adverse outcome emphasizes the need for earlier access to HAART.     

AIDS-defining illnesses: a comparison between before and after commencement of highly active antiretroviral therapy (HAART)

Attempts to address the significant impact of HAART on medical variables on the Malaysian HIV/AIDS population have yet to be evaluated. This study aims to analyze the proportions of AIDS-defining illnesses (ADIs) before and after HAART. A retrospective study was carried out on 128 new cases of HIV infected patients who first commenced HAART in 2004 at the national HIV reference center. Before commencement of HAART, 76 clinical episodes of ADIs were recorded in 52 patients. Most common being pulmonary Mycobacterium tuberculosis (28.9%), PCP (27.6%) and disseminated and extrapulmonary Mycobacterium tuberculosis (11.8%). During HAART, 8 clinical episodes of ADIs were documented in 7 patients with a median time of onset of 10 weeks after initiation of HAART (range, 4-36 weeks). The median CD4 count at the time of the commencement of HAART for these patients was 11 cells/mm(3). ADIs reported include PCP (2 episodes), disseminated and extrapulmonary Mycobacterium tuberculosis (2 episodes), extrapulmonary cryptococcosis (1 episode), esophageal candidiasis (1 episode), recurrent pneumonia (1 episode) and disseminated or extrapulmonary histoplasmosis (1 episode). Three (37.5%) of these occurred despite a reduction of viral load by at least 2 log(10) and an increased in the CD4 cell count. In conclusion, ADIs can still present after the initiation of successful HAART especially in those with CD4 counts below 100 cells/mm(3). In Malaysia, ADIs are the major causes of HIV/AIDS associated morbidity and mortality, thus increased awareness on the management of these illnesses is warranted especially in the months following HAART.     

Retrospective analysis of suspending HAART in selected patients with controlled HIV replication

We sought to determine the consequences of stopping highly active antiretroviral therapy (HAART) in a group of 41 HIV-infected individuals with undetectable HIV viral loads and CD4+ counts greater than 500 cells per microliter for 6 months or more. Clinical and laboratory parameters were monitored, as was the time to HAART reinitiation. Three months after HAART interruption, the median CD4+ count declined by 162 cells per microliter and HIV viral load increased by 24,000 copies per milliliter. Over the next year, CD4+ counts continued to decrease by an average of 11 cells per microliter per 3-month intervals. In contrast, HIV viral loads remained stable over the same period. Five of 7 patients (71%) with elevated cholesterol levels and 6 of 13 patients (46%) with elevated triglyceride levels had these values normalize after stopping HAART. After a median of 21 months follow-up, 26 of 41 patients (63%) have restarted HAART. Patients with Centers for Disease Control (CDC) HIV/AIDS C classification were more likely to restart HAART than those with A or B classification (p = 0.008). Reasons for HAART restart included clinical events in 8 patients. Fifteen patients restarted HAART for immunologic reasons: CD4+ count less than 300 cells per microliter (n = 7); HIV viral load greater than 55,000 copies per milliliter (n = 3); or both (n = 5). Three patients restarted HAART because of personal preference. Within 4 months, all 26 patients who restarted HAART achieved HIV viral loads less than 50 copies per milliliter. Although patients were able to rapidly achieve nondetectable HIV viral loads after restarting HAART, the inability to foresee clinical events among 8 patients (20%) is disconcerting. We advise caution before HAART interruption, particularly for those patients with a preceding history of significant HIV-related complications.     

Kinetics of lactate metabolism after submaximal ergometric exercise in HIV-infected patients

Objectives It is unknown whether high levels of lactate result from enhanced production or decreased degradation. We therefore investigated differences in the kinetics of plasma lactic acid in HIV‐infected patients receiving or not receiving highly active antiretroviral therapy (HAART) and in uninfected controls after submaximal ergometric exercise. Methods Ten healthy controls, 11 HIV‐infected therapy‐naïve patients, 15 HIV‐infected patients on HAART with normal baseline lactate levels, and nine HIV‐infected patients on HAART with elevated baseline lactate levels >2 mmol/L performed 10 min of ergometric exercise, with a heart rate of 200 beats/min minus age. Lactate levels were measured at baseline, at the end of exercise and 15, 30, 45, 60 and 120 min thereafter. Results Mean baseline lactate levels were 1.4, 1.5, 1.5 and 2.8 mmol/L in the controls, the therapy‐naïve patients, the patients on HAART with normal lactate levels and the patients on HAART with elevated lactate levels, respectively. Maximum lactate levels after exercise were similar in all groups (9.7, 9.4, 9.0 and 10.1 mmol/L, respectively). Significant differences were found in the slope of lactate decline between controls and untreated individuals (P=0.038) and between patients on HAART with normal baseline lactate and patients on HAART with elevated baseline lactate (P=0.028). Conclusions Differences in lactate metabolism do exist between healthy controls and HIV‐infected therapy‐naïve individuals. Thus, HIV infection in itself may influence lactate levels. Elevated baseline lactate levels are associated with a delayed decline of lactate after exercise. These results could be explained by impaired lactate clearance. Lactate production upon exercise does not seem to be affected by baseline lactate levels.     

Initial observations on the efficacy of highly active antiretroviral therapy in the treatment of HIV-associated autoimmune thrombocytopenia

BACKGROUND: Immune thrombocytopenic purpura (ITP) occurs in as many as 40% of patients infected with the human immunodeficiency virus (HIV). We sought to evaluate the effect of highly active antiretroviral therapy (HAART) on platelet counts in such patients. METHODS: Data collected from 11 homosexual men with HIV-associated ITP and < or = 50 x 10(9) platelets were analyzed after they were placed on HAART. At initial evaluation, 7 patients were antiretroviral naive, 2 were taking zidovudine alone, and 2 were receiving combination antiretroviral therapy for known HIV infection. For 6 patients with <30 x 10(9) platelets, prednisone was initially coadministered with HAART. The primary outcome measure was the platelet count response to HAART, which was measured weekly until counts had normalized on 3 consecutive occasions, then every 3 months while on HAART. Secondary outcome measures were HIV-viral RNA levels and CD4+ cell counts. RESULTS: One month after the initiation of HAART, 10 evaluable patients had an increase in mean platelet count. This improvement was sustained at 6 and 12 months' follow-up for 9 of 10 evaluable patients. Increases in mean platelet count at 6 and 12 months of the 9 responders were statistically significant. The range of follow-up in the 9 responders is 21 to 46 months (median, 30 months), with no thrombocytopenic relapses. The 9 long-term platelet responders have been maintained on HAART and at 12 months had a mean reduction of > 1.5 log10 in HIV viral RNA serum levels and a marked improvement in CD4+ T-lymphocyte cell count. CONCLUSION: HAART seems to be effective in improving platelet counts in the setting of HIV-associated ITP, enhancing CD4+ cell counts, and reducing HIV viral loads.     

Evolution of coinfection with human immunodeficiency virus and hepatitis C virus in patients treated with highly active antiretroviral therapy.

A retrospective analysis of data from a cohort of patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) who were treated with highly active antiretroviral therapy (HAART) at 3 infectious diseases units in northern Italy was performed. While the patients were receiving HAART, CD4(+) cell counts significantly increased and HIV RNA serum levels decreased. However, no significant overall changes in alanine aminotransferase (ALT) levels and HCV RNA serum levels were observed. Fifteen (4.6%) of 323 patients died within 3 years of follow-up; death was related to cirrhosis in 5 patients (1.6%). No significant difference was observed between cirrhosis-related mortality and mortality related to other causes. Patients with ALT levels >4 times the normal values at initiation of HAART showed a significant decrease in ALT levels, whereas patients with normal ALT levels at initiation of HAART showed a significant increase over time, suggesting that HAART may have long-term beneficial or detrimental effects, depending on patient characteristics.     

Alcohol Consumption and HIV Disease Progression: Are They Related?

BACKGROUND: The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). METHODS: We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. RESULTS: No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p = 0.006). CD4 cell counts in those with moderate (368 cells/microl) and at-risk (360 cells/microl) alcohol use were lower than for subjects who reported none (426 cells/microl; p = 0.07). CONCLUSION: Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression.     

Appendicitis in HIV-infected patients during the era of highly active antiretroviral therapy

Background

Limited studies have suggested increased incidence rates and unusual clinical presentations of appendicitis among HIV‐infected patients during the pre‐highly active antiretroviral therapy (HAART) era. Data in the HAART era are sparse, and no study has evaluated potential HIV‐related risk factors for the development of appendicitis.

Methods

We retrospectively studied 449 HIV‐infected patients receiving care at a US Naval hospital involving 4750 person‐years (PY) of follow‐up. We also evaluated the rates of appendicitis among HIV‐negative persons at our medical facility. We compared demographics, HIV‐specific data, and HAART use in HIV‐infected patients with and without appendicitis.

Results

Sixteen (3.6%) of 449 patients developed appendicitis after HIV seroconversion. The incidence rate was 337 cases/100 000 PY, more than fourfold higher than among HIV‐negative persons. Eighty‐eight per cent of cases among HIV‐infected patients had an elevated white blood count at presentation, 39% were complicated, and 64% required hospitalization. HIV‐infected patients with appendicitis compared with those who did not develop appendicitis were less likely to be receiving HAART (25 vs. 71%, P<0.001), had higher viral loads (3.5 vs. 1.7 log₁₀ HIV‐1 RNA copies/mL, P=0.005), and were younger (median age of 30 vs. 41 years, P<0.002). In the multivariate model, receipt of HAART remained protective [odds ratio (OR) 0.21, P=0.012] for appendicitis, while younger age was positively associated (OR 1.08, P=0.048) with appendicitis.

Conclusion

Acute appendicitis occurs at higher incidence rates among HIV‐infected patients compared with the general population. Our study demonstrates that the lack of HAART may be a risk factor for appendicitis among HIV‐infected patients; further studies are needed.     

300例艾滋病患者高效抗逆转录病毒治疗后免疫重建规律探讨

目的探讨高效抗逆转录病毒治疗（HAART）对中国南部地区艾滋病患者的免疫重建规律。方法收集近3年来300例患者的完整资料,按基线CD4^＋T细胞数分为A、B、C三组,观察基线及治疗1、3、6、12月末CD4^＋T淋巴细胞数、12月末血浆病毒载量（VL）、临床症状和毒副作用。结果抗病毒治疗12月末300例患者CD4^＋T淋巴细胞计数平均上升127个／1,以治疗3月后增长明显,3、12月末与基线CD4^＋T淋巴细胞计数比较差异有显著性（P〈0．05）;12月末273例（91％）患者血浆病毒载量（VL）〈5copies/ml,27例（9％）患者病毒载量（VL）〉50copies/ml,高病毒载量A组16例,C组4例;A组与C组比较差异有显著性（P〈0．05）;药物不良反应主要是外周神经炎（35．4％）、骨髓抑制（18．2％）、皮疹（15．2％）、肝功能损害（12．1％）、乳酸酸中毒（12．1％）和肾结石（6．1％）。结论HAART治疗对中国南部地区的艾滋病患者有效,能够实现免疫重建,但存在较多毒副作用。