Osteonecrosis in Patients Infected With HIV

Metabolic complications of HIV therapy in children.

The long-term effects of fat metabolism, storage and utilization in HIV-1 infected patients on highly active antiretroviral therapy (HAART) including a protease inhibitor are profound and cause increasing concern. The main importance of these lipid/metabolic disorders lies in their assumed contribution to an increased risk of coronary heart disease (CHD). In the general population increased levels of lipoprotein(a) [Lp(a)] constitute an independent risk factor for CHD by itself as well as in combination with increased levels of cholesterol and low density lipoprotein (LDL)-cholesterol, respectively. Two hundred and fifty-six patients with 27 +/- 7 months HAART and 84 treatment-naive HIV-1 positive patients were screened for cardiovascular risk factors. The subjective perception of fat wasting and/or accumulation in different sites of the body, which was possible to evaluate in 235 patients on HAART and 73 treatment-naive patients, the levels of plasma triglycerides (TG), cholesterol, LDL and high-density lipoproteins (HDL)-cholesterol, LDL/HDL ratio and Lp(a) were measured. Of the patients on HAART, 42% (98/235) reported abnormal fat distribution as compared with 4% (3/73) of the treatment-naive patients (P<0.0001). The levels of TG, cholesterol and LDL-cholesterol, but not HDL-cholesterol or Lp(a) were higher (P<0.0001) in the HAART group as compared with the naive group. Very high Lp(a) levels (> 700 mg/l) were more common among HAART patients as compared with naive, 14% (36/256) vs 2% (2/83); P=0.0022. The Lp(a) levels correlated to the levels of LDL-cholesterol, but not to total cholesterol, HDL-cholesterol or TG, and did not differ between patients with and without subjective perception of abnormal fat distribution. A significant number of the HAART patients had very high levels of Lp(a) and various combinations of increased lipid values associated with considerably increased risk for CHD. The elevation of Lp(a) did not relate to any other clinical or laboratory parameter than to LDL-cholesterol.

Metabolic disorders associated with atherosclerosis and cardiovascular disease have been described in "HIV-infected" individuals. We investigated (i) whether normotensive "HIV-infected" individuals and hypertensive patients have similarities regarding their arterial elastic properties and (ii) the effect of highly active antiretroviral therapy (HAART) and metabolic factors on arterial stiffness. In a case-control study, we compared measurements of pulse wave velocity (PWV), arterial blood pressure, and markers of metabolic profile in 56 normotensive, "HIV-infected" patients (mean age 40 +/- 13 years) to 28 age- and sex-matched newly diagnosed untreated patients with hypertension and 28 healthy individuals. "HIV-infected" patients had higher PWV than healthy controls but lower PWV than hypertensives (8.1 +/- 1.4 m/s vs. 6.7 +/- 1.1 m/s vs. 9.0 +/- 1.0 m/s, P = 0.003 and 0.01, respectively). However, patients on HAART had similar PWV with hypertensives (8.4 +/- 1.4 vs. 9.0 +/- 1.0 m/s P = 0.25). Patients on HAART had higher PWV than patients without (8.4 +/- 1.4 m/s vs. 7.5 +/- 1.3 m/s, P = 0.03). Patients on HAART had higher total cholesterol, triglycerides, and diastolic blood pressure than patients naive to HAART (P < 0.05). In multivariate analysis, the independent determinants of increased PWV were HAART duration (unstandardized coefficient b v = 0.007, P = 0.04), serum cholesterol (b = 0.007, P = 0.04), mean or diastolic blood pressure (b = 0.049 and b = 0.060, P < 0.01). "HIV-infected" individuals have increased arterial stiffness compared to healthy controls. Patients on antiretroviral therapy have similarities regarding their arterial elastic properties with patients with untreated hypertension. There is an independent association between duration of antiretroviral therapy, cholesterol levels, and blood pressure with increased arterial stiffness in "HIV-infected" patients.

Are HIV-infected patients candidates for liver transplantation?

Summary: Insulin resistance (IR) in the context of highly active antiretroviral therapy (HAART) is becoming more common in HIV-infected patients. Patients with chronic hepatitis C virus (HCV) infection have an increased risk of IR and type 2 diabetes mellitus. A cross-sectional study was performed to investigate whether chronic HCV infection constitutes a risk factor for IR in HIV-HCV-coinfected patients undergoing HAART. Inclusion criteria were positive HCV viremia and a sustained increase of alanine aminotransferase of at least twice the normal value. A total of 29 HIV-HCV patients, 76 HIV patients, and 121 HCV controls were tested for IR and body mass index (BMI). IR was measured using the homeostasis model assessment. In HIV-HCV and HIV patients, fat redistribution and lipid profile were assessed. There was no significant difference in age, CD4 cell count, HIV viral load, or duration of HAART between the HIV-HCV and HIV groups. HIV-HCV patients and HCV controls had a significant increase in IR when compared with HIV patients (0.25 ± 0.28 and 0.21 ± 0.34 versus 0.04 ± 0.37; p = .01 and p = .003, respectively). Lipoatrophy was observed more frequently in HIV-HCV patients in comparison with HIV patients (41% versus 14%; p = .003). In HIV-HCV patients, total cholesterol and triglyceride levels were significantly lower than in HIV patients. In multivariate analysis, IR, BMI, triglyceride levels, and peripheral fat wasting were the independent variables associated with HCV infection. Our findings suggest that chronic HCV infection is a significant factor associated with the development of metabolic abnormalities and with modifications in body composition in HIV patients receiving antiretroviral treatment.

Renal disease is a leading cause of morbidity in HIV-infected adults in the highly active antiretroviral therapy (HAART) era. Cystatin C has been proposed as a more sensitive marker of renal function, but it may be affected by ongoing inflammation. We aimed to study the cystatin C levels in a cohort of HIV-infected pediatric patients at 3 Spanish centers. This is a multicenter cross-sectional observational study. Renal function was assessed by means of first morning urine protein/creatinine and albumin/creatinine ratios and creatinine-estimated glomerular filtration rates (GFRs), together with the following inflammation markers: cystatin C, reactive C protein, β-2-microglobulin and 25(OH)-vitamin D levels. A control group of healthy children and adolescents was used. Eighty-three patients (51 females, median age: 13.3 years; 32 males, median age: 13.6 years) and 44 controls (24 females, median age: 12.2 years; 20 males, median age: 10.9 years) were included. Among the former, mean CD4 cell count was 860/mm, 29(35%) patients had a previous AIDS diagnosis, 73(88%) were on HAART and HIV viremia was undetectable in 61(73%). No differences in cystatin C levels were observed between the 2 groups. In HIV-infected patients, cystatin C levels correlated with GFR (r = -0.27; P = 0.01), age at first HAART (r = -0.21; P = 0.05), and β-2-microglobulin (r = 0.569; P < 0.01). In multivariate analysis, lower GFR (P = 0.014) and higher β-2-microglobulin levels (P = 0.001) remained as independent risk factors for higher cystatin C values. Cystatin C values were associated with GFR and β-2-microglobulin. Cystatin C may be useful as a marker of renal function in HIV-infected pediatric patients, independently of ongoing inflammation or viremia.

We were very interested to read the article by Dean et al. [1] on the treatment of tuberculosis (TB) in HIV-infected patients. Additional data shedding light on this complex and important problem [2] are very welcome. The authors recommend starting highly active antiretroviral therapy (HAART) early (within the first 2 months of TB therapy) in patients with a CD4 cell count of less than 100 × 106/l. However, the basis for such a recommendation is not clear from the data presented. The critical aspect of the study design is the separation of patients. Two major groups are compared: those who received no HAART during TB therapy, and those who had HAART concomitant with TB therapy. The latter group included a number of patients (18%) who were already on HAART at the time of the diagnosis of TB, and all patients starting HAART at any time between 0 and 14 months after starting TB treatment. The comparison is thus between no HAART and HAART at any time after the start of TB therapy. The use of HAART at any time was associated with fewer deaths and AIDS-defining illnesses, but such an observation does not allow one to reach conclusions about the optimum timing of the initiation of HAART. The key question for most clinicians, as the authors’ recommendations indicate, is not whether any HAART at any time is useful, but whether early antiretroviral treatment is better than delayed treatment. Because the median time of the initiation of HAART was in fact 2 months, it would have been interesting to compare patients starting therapy within 2 months with those who started treatment after the induction phase, and to separate out those patients already on antiretroviral therapy when TB developed. The latter group present different issues from patients not known to be HIV infected when TB develops, and are most usefully considered separately. Physicians with experience in the field are only too aware of the problems of HAART in the first 2 months of quadruple TB treatment. Confirmation of the extraordinarily high rate of adverse drug events (54% of patients), many requiring an interruption of therapy (34% of patients), is a valuable contribution of the study. The adverse events occurred predominantly in the first 2 months of TB therapy, and were nearly twice as likely in those on concomitant HAART. A further potential disadvantage of early HAART is the possibility of precipitating more frequent or severe immune reconstitution reactions [3,4]. Finally and importantly, because of drug interactions and the increased pill burden (especially with antiretroviral therapy in the first 2 months of TB treatment) that may affect adherence adversely, concerns remain over the long-term effects of concurrent HIV and TB therapy on viral suppression and TB relapse rates. As stated, such long-term effects could not be assessed in this study. Of the potential benefits of early HAART, clearly an associated reduction in mortality, if causal, overrides all other considerations. However, any association between the use of HAART and improved outcome in an uncontrolled retrospective review needs to be interpreted with caution. There was little discussion of this critical issue, and it would be very useful to see data on the timing and probable causes of death. Given the fact that the median time to the initiation of HAART was 2 months, if a significant number of these deaths occurred early, the apparent association of HAART with survival may have resulted from selection bias, with survivors having a greater chance of going on to receive HAART. Regarding the number of further AIDS-defining illnesses, it would be useful to know what these were. Of note is the fact that two-thirds occurred after the first 2 months and none occurred in the first month. The number of such episodes prevented by early treatment may therefore be small. With an increasing understanding of the drug interactions involved in concomitant TB and HIV therapy [2], and the publication of some outcome data [5], starting antiretroviral therapy in the continuation phase of TB treatment has become easier. The study suggests that such an approach is associated with a reduction in AIDS-defining illnesses in the short term. The development of simpler antiretroviral regimens and TB treatment by directly observed therapy also makes HIV therapy in the first 2 months of TB treatment a realistic option. However, many of the potential problems with concurrent therapy apply particularly to this period. We need additional data, ideally from controlled prospective studies with adequate follow-up, to determine whether HAART in the first 2 months of TB treatment is in our patients’ best interests. Thomas. S. Harrisona Derek C. Macallana Charlotte F. J. Raynerb Mark Wansbrough-Jonesa

New antiretroviral drugs and approaches to HIV treatment.

suPAR associates to glucose metabolic aberration during glucose stimulation in HIV-infected patients on HAART

Homocysteinaemia in HIV-infected patients treated with highly active antiretroviral therapy.

Patients with HIV infection often complain of cognitive disturbances, which can be related to AIDS dementia or HIV-associated encephalopathy (HIVE). We investigated the impact of highly active antiretroviral therapy (HAART) in comparison with other therapeutic regimens on the progression of these cognitive disturbances as measured by visual event-related potentials (ERP). In a cross-sectional study, 214 patients without secondary neuromanifestation of their infection were divided into four groups with respect to their treatment status for 1 year before examination: (1) without antiretroviral treatment, (2) zidovudine monotherapy, (3) zidovudine in combination with didanosine, zalcitabine, or lamivudine, and (4) HAART. In a prospective longitudinal study, we divided 54 patients into three groups: (1) without antiretroviral treatment, (2) zidovudine monotherapy, and (3) HAART. Latencies of the P2, N2, and P3 components and the amplitude of the P3 component were evaluated. A significant negative correlation between CD4(+) lymphocyte cell count and P3 latency was found in all patients (p < 0.004). In the cross-sectional study, P3 latency was significantly decreased in the HAART group as compared with patients with no antiretroviral treatment (p < 0.01). During the 1-year period of the prospective longitudinal study, the P3 latency significantly increased in patients with no antiretroviral treatment (p < 0.05) and significantly decreased in patients with HAART (p < 0.05). In summary, these results suggest that HAART has an improving therapeutic effect on cognitive processing in HIV-infected patients and is superior to zidovudine monotherapy or dual antiretroviral treatment. Because prolongation of ERP might in part reflect HIVE, we conclude that this condition represents an indication for HAART.

Background: In India, there is a lack of awareness and inadequate knowledge about use of Highly Active Antiretroviral Therapy (HAART) due to social stigma leading to intentional non-adherence among Human Immunodeficiency Virus (HIV) infected patients thus, Educational Intervention (EI) must be sought. Need for the study: There is a need for an EI program for HIV-infected patients for improving adherence to Antiretroviral Therapy (ART). Aim: The aim of the study was to evaluate the impact of an EI on use of HAART and its effect on adherence behavior in Intervention Care Group (ICG) in comparison with Standard Care Group (SCG) in HIV infected patients. Methods: A prospective, randomized, controlled study was conducted at Kasturba hospital Manipal from August 2009 to May 2012 in HIV infected patients. The baseline response for Knowledge, Attitude, Belief, and Practice (KABP) questionnaire was assessed. Block randomization was used to assign the patients to the SCG and ICG. In ICG group, patients are educated every 4 weeks for a total of 16 weeks with Patient Information Leaflet (PIL), adherence counseling and awareness to Adverse Drug Reactions (ADRs) to ART by a clinical pharmacist. In ISG group, patients are given standard care for ART treatment by a clinician. Post KABP response was documented in both groups at 16th week and adherence rate was measured. Repeated-measures Analysis of Variance (RANOVA) was used for the comparison of pre and post total KABP responses between ICG and SCG. Results: A total of 256 HIV positive patients were enrolled. Out of which 16 patients were excluded because they were on traditional medicines and 240 HIV-infected patients with HAART were finally included in the study, of whom 120 (89 [74.2%] men, 31[25.8%] women) were randomly assigned to the ICG and 120 (99 [82.5%] men, 21[17.5%] women) to the SCG. Pre and post KABP responses significantly increased with mean ± standard deviation (SD) (p<0.001) and greater than 95% of adherence (p<0.001) was reported in ICG after EI in comparison with SCG. Conclusion: The EI program on use of HAART in this study changed their intentional non-adherence behavior, negative beliefs and social stigma.

Highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of patients with human immunodeficiency virus (HIV). Specific toxicities cited for HAART include elevations in serum levels of total cholesterol and triglycerides, reduction in high-density lipoprotein cholesterol, alterations in the distribution of body fat, increases in insulin resistance, and diabetes, which are major risk factors for cardiovascular disease (CVD). The majority of the studies examining the incidence of CV events demonstrated an increase in CV event rate with HAART in the HIV-infected population. Overall, the CVD risk appears to be greater in the HIV-infected population than in the general population, and the increased CV risk is associated with HAART, particularly with protease inhibitor use. Despite the relative risk (RR) for CVD being significantly high (the hazard ratio for myocardial infarction ranging between 1.3 and 7.1), the absolute risk for CVD remains low, with the CV event rates ranging between one and seven events per 1000 person-years. Although there is general consensus that the benefits of HAART far outweigh toxicity-related risks of the treatment with HAART, prolonged survival among HIV-infected patients will likely support the use of different antiretroviral regimens with potentially less CV toxicity in the future.

Background: Even though highly active antiretroviral therapy (HAART) for HIV (Human Immune Deficiency) patients has considerably improved viral load suppression, more people still struggle to reduce viral loads. The aim of the study was to determine the associated factors of virological failure in HIV patients on antiretroviral therapy (ART) in the Upper East Region of Ghana. Methods: A retrospective cross-sectional study involving 366 participants aged 15 years and above who were on HAART for six (6) months or longer with viral load results in 2020. Bivariate and multiple logistic regression analyses were conducted to identify the determinants of virological failure among HIV patients at 95% confidence interval (C.I.) with a significant level pegged at a p value less than 0.05. Results: The prevalence of viral load failure was 47.0% and adherence to antiretroviral therapy was 62.6% among patients on HAART. The significant predicators of virological failure were basic education (AOR (adjusted odds ratio) = 7.36, 95% C.I = 4.91–59.71), High school/Vocational /Technical education (AOR = 4.70, 95% C.I. = 1.90–9.69), monthly salary/income ˂ GHS 375.00 (AOR = 7.20, 95% C.I. = 1.73–29.95), duration on ART for ˂1 year (AOR = 0.27, 95% C.I. = 0.10–0.75), ART regimen (Tenofovir + Lamivudine + Efavirenz) (AOR = 3.26, 95% C.I. = 1.95–11.25), 3–5 times missed medication per month (AOR = 2.86, 95% C.I. = 1.34–6.08) and ≥6 missed medication per month (AOR = 23.87, 95% C.I. = 10.57–53.92). Conclusion: Educational status, salary/income, ART duration, ART combination regimen, and number of doses missed were statistically significantly associated with virological failure in patients on antiretroviral therapy. The majority of the respondents adhered to ART, which led to moderate viral load suppression but lower than the target for 2020. There is the need to strengthen the ongoing accelerated social behavior change communication among patients on ART to enhance adherence in order to attain the new UNAIDS target of 95% viral load suppression by 2030 in the Upper East Region of Ghana.

Acceleration of confirmed coronary artery disease among HIV-infected patients on potent antiretroviral therapy.