Anemia in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Anemia is common in HIV infection, particularly in advanced disease states. We wished to determine how highly active antiretroviral therapy (HAART) and other factors affected the level of hemoglobin in HIV infection. METHODS: We analyzed data from 905 patients receiving care at Johns Hopkins in Baltimore, Maryland after July 1, 1996. Analyses were done of hemoglobin levels obtained at baseline and during 1 year of follow-up in patients who received and did not receive a HAART regimen. Use of HAART and other demographic and clinical factors were examined. RESULTS: Eleven percent of patients had a hemoglobin count <10 g/dL, 27% had a hemoglobin count 10 to 12 g/dL, and 21% had a hemoglobin count of >14 g/dL at baseline before HAART was started. During 1 year of follow-up, use of HAART was associated with a hemoglobin levels >14 g/dL in 42% of patients, irrespective of use of zidovudine as part of HAART regimen, compared with 31% of patients who did not use HAART. In multivariate analysis, use of HAART was strongly associated with not having anemia during 1 year of follow-up, adjusting for patient gender, race, injection drug use history, baseline CD4 and HIV-1 RNA levels, and anemia treatments. CONCLUSIONS: HAART is an effective treatment of the anemia of HIV infection. Patients who continue to have symptomatic anemia while receiving HAART may need additional intervention.     

Improvement of anemia among HIV-infected injection drug users receiving highly active antiretroviral therapy

Although anemia is common during HIV infection, it is unclear whether potent antiretroviral therapy would improve or worsen anemia. We conducted a study to examine the impact of highly active antiretroviral therapy (HAART) on anemia in a cohort of HIV-positive injection drug users (IDUs) in Baltimore, Maryland. At baseline, the overall prevalence of anemia was 40%. During mean follow-up of one year, among 102 subjects who received HAART, there was a mean increase in hemoglobin of 3.6 +/- 1.7 g/L (p =.0003) [corrected] and a mean decrease in log(10) plasma HIV load of 0.25 +/- 0.06 copies/ml (p <.0002) [corrected]. Among 103 control subjects who were not receiving antiretroviral medications, there was a mean decrease in hemoglobin of 4.2 +/- 1.1 g/L (p <.04) [corrected] and mean increase in log(10) plasma HIV load of 0.78 +/- 0.17 copies/ml (p <.0001) [corrected]. Multivariate analysis using mixed linear models showed that HAART was associated with an increase of hemoglobin of 0.223 g/L per month (p <.0001) after adjusting for body mass index, opportunistic infections, and gender. HAART was associated with an improvement in anemia, and potential mechanisms that may be involved include a reduction in opportunistic infections and the anemia of chronic disease and an improvement in nutritional status.     

Sexual dysfunction in HIV-infected patients treated with highly active antiretroviral therapy

Sexual disturbances develop in some patients treated with highly active antiretroviral therapy (HAART). To evaluate sexual dysfunction and the influence that different antiretrovirals could have on those parameters, we conducted a prospective study in patients with stable clinical condition attending an HIV outpatient clinic. A total of 351 evaluations were performed in 189 HIV-infected men, who were interviewed about symptoms of sexual dysfunction. Sexual hormones as well as other clinical and laboratory parameters were also measured at the time of each evaluation. The mean CD4 count was 451.1 x 10(6) cells/L, and viral load was undetectable in two thirds of the determinations. The prevalence of sexual dysfunction was 19.5% overall, but it was influenced by treatment, particularly (although not exclusively) by protease inhibitors (PIs) (27.1% vs. 3.8% for untreated patients). Sexual dysfunction was not related to hypophyseal or gonadal hormonal values. Although several parameters were associated with sexual dysfunction in the univariate analysis, only antiretroviral treatment was significantly predictive of this disorder in a logistic regression analysis. Sexual dysfunction is common in HIV-infected patients in stable clinical condition receiving HAART, and all antiretroviral drugs, particularly PIs, seem to be related to it. Sexual dysfunction in these patients is not related to hormonal causes.     

Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy

Circulating soluble urokinase plasminogen activator receptor (suPAR) reflects the immune and pro-inflammatory status of the HIV-infected patient. Highly active antiretroviral therapy (HAART) suppresses suPAR. Independent of the immune response to HAART, suPAR remains elevated in some HIV-infected patients, reflecting possibly a low-grade pro-inflammatory state. Low-grade inflammation has been implicated in insulin resistance and other features of dysmetabolism. Accordingly it is hypothesized that circulating suPAR is associated with the metabolic status of HIV-infected patients on HAART. Fasting plasma suPAR was determined in 36 normoglycaemic HIV-infected patients on HAART (n = 18 lipodystrophic, and n = 18 non-lipodystrophic) who had estimated insulin sensitivity (Rd) and non-oxidative glucose disposal (NOGM) by euglycaemic hyperinsulinaemic clamps, indirect calorimetry, and glucose tracer infusion. Five patients had circadian suPAR concentrations measured (24 hr, 20 min-intervals). suPAR and non-HDL-cholesterol were higher and Rd, NOGM, and limb fat were lower in lipodystrophic patients than in non-lipodystrophic patients (P < 0.05). suPAR correlated positively with non-HDL-cholesterol and inversely with Rd, NOGM and limb fat (P < 0.005, n = 36). suPAR also correlated positively with leukocyte count and TNF-alpha (P < 0.01, n = 36) but not with IL-6. In multiple regression analyses suPAR was a stronger predictor of dysmetabolism than TNF-alpha and IL-6. Circadian suPAR did not systematically fluctuate. In conclusion, suPAR may reflect the metabolic status of the HIV-infected patient on HAART, thus linking low-grade inflammation, immune constitution, lipid and glucose metabolism, and fat redistribution. Circadian suPAR concentration appeared stable, suggesting that sampling schedule does not affect measurement. Further studies addressing whether suPAR predicts lipodystrophy and dysmetabolism in HIV-infected patients are warranted.     

Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients

OBJECTIVES: To assess the effect of antiretroviral therapy (ART) adherence on survival in HIV-infected patients. DESIGN: Cohort study at a single hospital in Barcelona, Spain. METHODS: Data on HIV-infected patients older than 18 years of age who began ART during the period 1990 to 1999 were analyzed. Patients were considered nonadherent if the total dose of antiretroviral drug was less than 90% of that prescribed. Adherence was assessed through self-report and hospital pharmacy appointments. Cox regression with time-dependent variables was used. RESULTS: A total of 1219 patients were included. The first ART was with monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy in 45.8%. In multivariate analysis, the variables that presented significant differences with respect to mortality were clinical stage at the beginning of treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14-4.13), CD4 cell count (<200 cells/microL: RH = 5.89; CI: 3.44-10.10), type of treatment (monotherapy: RH = 9.76; CI: 4.56-20.90; bi-therapy: RH = 9.12; CI: 4.23-19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77-8.46). CONCLUSIONS: The modifiable factors most strongly associated with survival were type of treatment and adherence. It would be desirable to accompany therapy with intervention strategies intended to improve adherence.     

Non-AIDS-defining malignancies among HIV-infected patients in the highly active antiretroviral therapy era

In the highly active antiretroviral therapy (HAART) era, the incidence of AIDS-defining malignancies (ADMs) has declined significantly. On the other hand, the incidence of other malignancies not known to be associated with immunosuppression (non-ADMs) has not changed and remains significantly higher than in the general population. Some recent controlled studies even suggest that the incidence of selected non-ADMs has increased in the HAART era. These trends warrant a high index of suspicion for malignancies among HIV care providers and a renewed focus on understanding the mechanisms underlying the increased rates. Potential explanations for the higher non-ADM rates include longer survival of patients with HIV on HAART, with only partial immune recovery achieved in most patients; high incidence of human papillomavirus, Epstein-Barr virus, and hepatitis C virus coinfection in patients with HIV infection; and potential oncogenicity of long-term HIV infection or of long-term HAART.     

Pulmonary infiltrates in HIV-infected patients in the highly active antiretroviral therapy era in Spain

OBJECTIVE: To study the incidence, etiology, and outcome of pulmonary infiltrates (PIs) in HIV-infected patients and to evaluate the yield of diagnostic procedures. DESIGN: Prospective observational study of consecutive hospital admissions. SETTING: Tertiary hospital. PATIENTS: HIV-infected patients with new-onset radiologic PIs from April 1998 to March 1999. METHODS: The study protocol included chest radiography, blood and sputum cultures, serologic testing for "atypical" causes of pneumonia, testing for Legionella urinary antigen, testing for cytomegalovirus antigenemia, and bronchoscopy in case of diffuse or progressive PIs. RESULTS: One hundred two episodes in 92 patients were recorded. The incidence of PIs was 18 episodes per 100 hospital admission-years (95% confidence interval [CI]: 15-21). An etiologic diagnosis was achieved in 62 cases (61%). Bacterial pneumonia (BP), Pneumocystis carinii pneumonia (PCP), and mycobacteriosis were the main diagnoses. The incidences of BP and mycobacteriosis were not statistically different in highly active antiretroviral therapy (HAART) versus non-HAART patients. The incidence of PCP was lower in those receiving HAART (p =.011), however. Nine patients died (10%). Independent factors associated with higher mortality were mechanical ventilation (odds ratio [OR] = 83; CI: 4.2-1,682), age >50 years (OR = 23; CI: 2-283), and not having an etiologic diagnosis (OR = 22; CI: 1.6-293). CONCLUSIONS: Pulmonary infiltrates are still a frequent cause of hospital admission in the HAART era, and BP is the main etiology. There was no difference in the rate of BP and mycobacteriosis in HAART and non-HAART patients. Not having an etiologic diagnosis is an independent factor associated with mortality.     

Sexual dysfunction in 156 ambulatory HIV-infected men receiving highly active antiretroviral therapy combinations with and without protease inhibitors

We conducted a cross-sectional study of 156 ambulatory HIV-infected homosexual or bisexual men to assess and compare the prevalence and characteristics of sexual dysfunction according to treatment combinations (group A, protease inhibitor [PI] treatment; group B, no PI treatment; and C, PI treatment interrupted >1 month previously). The study was based on a self-administered 163-item questionnaire that included a French translation of the International Index of Erectile Function, five sections of the Derogatis Sexual Functioning Inventory, and open questions. Data analysis was performed using Mann-Whitney and Kruskal-Wallis H nonparametric tests (quantitative values) and chi2 tests (qualitative values) using SPSS software (SPSS, Chicago, IL, U.S.A.). One hundred fifty-six patients completed the study. The median age +/- SD of the patients was 40.5 +/- 7.7 years, and the median CD4+ cell count +/- SD was 415 +/- 236/mm3. One hundred eleven (71%) of 156 patients reported some degree of sexual dysfunction since the beginning of their treatment (65 [71%] of 91 group A patients; 15 [65%] of 23 group B patients; and 31 [74%] of 42 group C patients), with no significant difference among the groups. Of the 111 patients, 99 (89%) reported decrease or loss of libido, 76 (68%) reported orgasmic perturbation, 96 (86%) reported erectile dysfunction, and 65 (59%) reported ejaculation perturbation, with no significant difference among the three groups. There were no significant differences among the three groups regarding the International Index of Erectile Function and Derogatis Sexual Functioning Inventory scores. These data suggest that PI-based therapy does not seem to increase sexual dysfunction in this patient population.     

Long-term survival and serious cardiovascular events in HIV-infected patients treated with highly active antiretroviral therapy

There is continuing interest in the longer term effects of highly active antiretroviral therapy (HAART) on the risk of cardiopulmonary events. We assessed this using updated administrative data from an open retrospective cohort of HIV-infected persons receiving care from the US Veterans Affairs (VA). Information on 41,213 HIV-infected patients receiving VA care between January 1993 and December 2003 was included. Patients were followed for an average of 4 years or 168,213 person-years of follow-up. The death rate fell from 20.9 deaths per 100 patient-years of observation in 1995 to 5.2 deaths per 100 patient-years in 2003. In patient-level analysis, adjusted hazard ratios for death dropped precipitously for all races to a low of 0.18 (95% confidence interval: 0.15 to 0.23) at 72 months of exposure to HAART. Hazards for serious cardiovascular events remained near 1.0 for exposure to HAART, and hazards for serious cardiovascular events, stroke, or death were only slightly higher than for death alone. No selection effects or secular trends were found. The benefits of HAART continued to increase in the 8 years after introduction and with 6 years of individual use. The risk of serious cardiovascular events should be factored into individual patient management but does not pose an important public health risk.     

Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral therapy or receiving a first-line treatment

Background: The combination antiretroviral therapy (cART) has dramatically improved the life expectancy of patients with HIV infection, but may lead to several long-term metabolic abnormalities. However, data about the frequency of metabolic syndrome (MS) in HIV-infected people vary considerably across different observational studies.

Methods: The prevalence of MS among HIV-infected patients was evaluated by a cross-sectional study conducted among subjects naive to cART or receiving the first antiretroviral regimen and referring to our Clinics from January 2015 to December 2015. The diagnosis of MS was made based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), and International Diabetes Federation (IDF) criteria.

Results: The study recruited 586 patients: 98 naive to cART and 488 under the first antiretroviral treatment. The prevalence of MS, according to NCEP-ATP III criteria, was significantly higher among treated patients than among naive ones (20.9% vs. 7.1%; p = 0.014). The most frequently reported components of MS among treated patients were high triglycerides (44.3%), low high-density lipoprotein cholesterol (41.1%), and hypertension (19.7%). On multivariate analysis, long duration of HIV infection, low nadir of CD4 lymphocytes, high body mass index, current use of one protease inhibitor, and long duration of cART were significantly associated with a higher risk of MS, while current use of one integrase inhibitor was significantly associated with a lower risk of MS.

Conclusions: The non-negligible prevalence of MS among HIV-infected patients under cART requires a careful and periodic monitoring of its components, with particular attention to dyslipidemia and hypertension.     

Safety, tolerability, pharmacokinetics, and efficacy of an interleukin-2 agonist among HIV-infected patients receiving highly active antiretroviral therapy.

We sought to determine the safety, maximum tolerated dose, optimal dose, and preliminary dose efficacy of intermittent subcutaneously (s.c.) administered BAY 50-4798 among patients with HIV infection receiving highly active antiretroviral therapy (HAART) compared with patients receiving HAART alone. A phase I/II randomized, double-blind, dose-escalation study was conducted of the safety, tolerability, pharmacokinetics, and efficacy of s.c. BAY 50-4798 administered to HIV-infected patients already receiving stable HAART. There were no unexpected safety findings in a population of HIV-infected patients receiving HAART plus SC BAY 50-4798 as adjunctive therapy. BAY 50-4798 exhibited nearly dose-proportional pharmacokinetics, and accumulation was minimal during multiple-dose treatment. Limited efficacy data indicated that treatment with BAY 50-4798 caused at least a transient increase in CD4(+) T cell counts in some recipients, particularly at the early time points. In general, this effect appeared to increase with increasing dose. Bay 50-4798 was generally well tolerated across the dose range tested, but a lack of potent, sustained immunologic activity suggests that further optimization of dose and schedule will be necessary.     

Gender and hospitalization patterns among HIV-infected drug users before and after the availability of highly active antiretroviral therapy

We examined highly active antiretroviral therapy (HAART) era and pre-HAART era hospitalization rates among 604 HIV-infected drug users in a prospective study in Bronx, New York. Medical history and risk behaviors were elicited by semiannual interviews. Standardized medical record review abstracted discharge diagnoses for all hospitalizations. Hospitalization rates from January 1997 to December 2000 were compared with rates from January 1992 to December 1996. The rate of hospitalizations per 100 patient-years in the HAART era was 49.3 compared with 44.1 in the pre-HAART era (P = 0.13). Among women, the rate was significantly higher in the HAART era than in the pre-HAART era (68.1 vs. 49.4 hospitalizations per 100 patient-years, respectively; P = 0.01). In the second era, HAART users had lower rates than those who did not use HAART (37.2 vs. 83.4 hospitalizations per 100 patient-years, respectively; P < 0.001) for both HIV-associated and non-HIV-associated illnesses. Multivariate analysis revealed that in the HAART era, female gender (relative risk ratio = 1.72, P = 0.03) and not using HAART (relative risk ratio = 1.82, P = 0.02) independently predicted increased hospitalization risk. In the pre-HAART era, women were at independently higher risk of hospitalization (relative risk ratio = 1.36, P = 0.05). Among HIV-infected drug users, those who use HAART have a decreased risk of hospitalization; those who do not use HAART remain at high risk of continuing morbidity from both HIV-related and non-HIV-related illness and have high hospitalization rates.