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.     

HIV+ MALT lymphoma remission induced by highly active antiretroviral therapy alone

MALT lymphoma is usually described in association with Helicobacter pylori, HCV, HHV8, Campylobacter jejuni or in a setting of overreactive immunity. In HIV(+) patients, MALT lymphoma is most commonly described in children. We describe here an original case of HIV(+) MALT lymphoma with bronchial, conjuctival and laryngeal involvement for which a clinical and histopathological remission has been obtained with HAART alone. We conclude that HIV, as well as H. pylori, C. jejuni and HCV can target lymphogenesis in MALT lymphoma.     

HIV infection, highly active antiretroviral therapy and the cardiovascular system

Cardiovascular complications in the course of human immunodeficiency virus (HIV) infection are multifactorial and may be caused by the virus itself or by the related opportunistic infections and neoplasms. Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in peripheral artery and coronary artery diseases. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients candidate to antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk with the available guidelines.     

HIV infection in the era of highly active antiretroviral therapy: the Malaga Study

We analyse the characteristics of patients diagnosed with HIV infection in the highly active antiretroviral therapy era in the southeast of Spain. Data were collected on 470 HIV patients diagnosed between January 1997 and December 2002. The number of cases fell over recent years and HIV transmission was sexual in 70.5%. The mean CD4 lymphocyte count was 302.1 x 10(6)/L and the mean viral load 4.70 log(10). Diagnosis of HIV coincided with an AIDS-defining opportunistic illness in 30.6% of patients and a late diagnosis (CD4 < 200 x 10(6)/L) was made in 48.3% of patients. A late diagnosis was related to male gender (OR 2.50; 95% CI 1.20-5.12; P < 0.001) and AIDS case (OR 18.80; 95% CI 10.50-33.80; P < 0.00001). These results suggest that there has been a progressive reduction in new cases of HIV-infected patients, with the main route of transmission being sexual and that the diagnosis was late in almost half the patients.     

Osteoarticular complications related to HIV infection and highly active antiretroviral therapy.

With the significant increase in life expectancy for HIV-infected patients in the era of high potency antiretroviral therapy, major metabolic changes have been observed due to the prolonged period of the viral infection and the treatment itself. Osteoarticular changes resulting from these processes are mainly reported in long term HIV-infected patients receiving high potency antiretroviral therapy and include osteopenia/osteoporosis, osteonecrosis, carpal tunnel syndrome and adhesive capsulitis of the shoulder.     

Meta-analysis of adherence to highly active antiretroviral therapy in patients with HIV infection in China

With the widespread implementation of antiretroviral therapy in many countries, the HIV/AIDS epidemic has declined. However, little is known about the prevalence of adherence rate to Highly Active Antiretroviral Therapy (HAART) in patients with HIV infection in China. This is the first meta-analysis of cross-sectional studies of treatment adherence (≥ 95%) to HAART in Chinese patients. Both English (PubMed, PsycINFO, EMBASE, and Web of Science) and Chinese (WanFang, CNKI, and SinoMed) databases were systematically and independently searched by three investigators. Studies with adherence rate estimates of HAART were included. Adherence rate estimates of each eligible study were extracted and pooled using the random-effects model. A total of 40 studies conducted in China were eligible and analyzed. The mean rate of?≥?95% adherence to HAART was 81.1% (95%CI: 75.1%–88.0%, I²?=?97.3%) at one week, 80.9% (95%CI: 74.7%–85.9%, I²?=?96.6%) at one month, and 68.3% (95%CI: 46.1%–84.4%, I²?=?97.1%) at 3 months or longer. Subgroup analyses revealed that samples with no gender predominance, low education level, middle economic region, rural area, older age (42.3 years), and recent publication (2013 or later) were correlated to higher HAART adherence. The average rate of HAART adherence was relatively high in China, which indicates effective HIV/AIDS policy, prevention and control measures. However, the HAART adherence rate decreased over the study time period.     

Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection

Highly active antiretroviral therapy (HAART) regimens, especially those including protease inhibitors have been shown to cause, in a high proportion of HIV-infected patients, a metabolic syndrome (lipodystrophy/lipoatrophy, dyslipidemia, type 2 diabetes mellitus, insulin resistance) that may be associated with an increased risk of cardiovascular disease. A careful stratification of the cardiovascular risk of HIV-infected patients under HAART is needed according to the most recent clinical guidelines.     

Pulmonary manifestations of HIV infection in the era of highly active antiretroviral therapy.

STUDY OBJECTIVES: To determine whether the spectrum of HIV-related pulmonary disease seen by a university medical center Pulmonary and Critical Care Medicine Service has changed since the introduction of highly active antiretroviral therapy (HAART). DESIGN: Retrospective chart review. SETTING: A tertiary care university hospital. PATIENTS: All HIV-infected patients referred to the Pulmonary and Critical Care Medicine Service from January 1, 1993, through December 31, 1995 (era 1) and from July 1, 1997, through June 30, 2000 (era 2). INTERVENTIONS: Inpatient and outpatient charts were reviewed for data regarding patient demographics, CD4 cell counts, viral load levels, duration of HIV seropositivity, history of opportunistic infections, and final diagnosis. RESULTS: Pneumocystis carinii pneumonia (PCP) was less common in the HAART era than in the pre-HAART era, whereas bacterial pneumonia and non-Hodgkin's lymphoma (NHL) were more common in the HAART era than in the pre-HAART era. HAART was protective against PCP (odds ratio [OR], 0.37; confidence interval [CI], 0.16 to 0.89) in a manner dependent on the CD4 cell count. Patients receiving HAART were at increased risk for the development of bacterial pneumonia (OR, 2.41; CI, 1.12 to 5.17) and NHL (OR, 15.11; CI, 3.14 to 28.32). A history of PCP indicated a risk factor for bacterial pneumonia (OR, 2.14; CI, 1.13 to 4.04). A history of cytomegalovirus infection indicated a risk factor for NHL (OR, 6.0; CI, 1.27 to 28.32). CONCLUSIONS: There have been significant changes in the spectrum of HIV-related pulmonary complications seen by our Pulmonary and Critical Care Medicine Service in the HAART era.     

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.     

Virologic and immunologic response to highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) delays clinical progression to AIDS by suppressing viral replication, allowing the immune system to reconstitute. These virologic and immunologic consequences do not occur uniformly among HAART users; markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while under HAART. In this paper, we review studies describing the heterogeneous virologic and immunologic progression following the initiation of HAART, and update findings obtained in the Multicenter AIDS Cohort Study that show that CD4 cell count and history of antiretroviral therapy at the time of initiation are independent determinants of response.     

Intracellular cytokines in the acute response to highly active antiretroviral therapy

OBJECTIVES: Successful highly active antiretroviral therapy (HAART) is usually associated with a rapid decline in HIV plasma RNA levels and a gradual increase in CD4 T cells. We examined whether changes in cytokine production and profile precede other immunological changes and whether these might occur in temporal association with plasma HIV RNA changes. DESIGN AND METHODS: Eleven HIV-1-infected patients were enrolled into a prospective cohort study; eight patients were naive to antiretroviral therapy. Blood samples were collected pre-therapy (week 0) and at 1, 2, and 3 weeks post-initiation of therapy. RESULTS: All 11 patients enrolled remained on triple HAART for 1 week, eight for 2 weeks, and six for > or = 3 weeks. When compared to week 0, these patients had a > or = 2-log10 decline in HIV plasma RNA levels and/or a decline to < or = 400 copies/ml by week 3 of therapy (p = 0.004). The numbers and percentages of CD4 and CD8 T cells, and the percentage of naive, memory, and activated T cells did not change significantly between weeks 0 and 1 or 0 and 3. Of all the immune parameters examined only: the percentage of CD4 T cells spontaneously producing tumor necrosis factor (TNF)-alpha (median, 2.4 versus 0.5% P = 0.025); the percentage of CD8 T cells spontaneously producing TNF-alpha (median, 0.6 versus 0.2% P = 0.037); and the percentage of CD3 T cells spontaneously producing interleukin-4 (median, 1.8 versus 0.8% P = 0.004) changed significantly between weeks 0 and 3. CONCLUSIONS: In these patients, decreases in the percentage of T cells spontaneously producing TNF-alpha or interleukin-4 preceded changes in CD4 T cells. If confirmed by others, these observations may be useful as early predictors of response to and early failure of HAART.     

Intensive care in patients with HIV infection in the era of highly active antiretroviral therapy

STUDY OBJECTIVES: The use of highly active antiretroviral therapy (HAART) has dramatically improved morbidity and mortality in patients with HIV infection. The types of critical illness and their outcomes in HIV-infected patients in recent years is unknown. DESIGN: We reviewed the medical records of all patients admitted to the Medical ICU of Beth Israel Medical Center, NY, from January to June 2001 and compared their characteristics with patients admitted to the same unit from November 1991 to October 1992. RESULTS: Of 441 admissions in the first half of 2001, 63 admissions (14%) were in 53 HIV-seropositive patients. There were 65 admissions to the Medical ICU during the 1-year period spanning 1991 to 1992. Compared with the earlier period, the 2001 patients were more likely to be black (52% vs 26%, respectively; p < 0.01) and injection drug users (75% vs 48%, respectively; p < 0.01), and were less likely to be white (11% vs 23%, respectively; difference not significant) and homosexual men (6% vs 26%, respectively; p < 0.01). In 2001, patients were less likely to be admitted with respiratory failure (22% vs 54%, respectively; p < 0.01) and with Pneumocystis jiroveci pneumonia (formerly referred to as Pneumocystis carinii) [3% vs 34%, respectively; p < 0.001], and were more likely to be admitted with non-HIV-related diseases (67% vs 12%, respectively; p < 0.001). Overall survival was much higher in the later period (71% vs 49%, respectively; p < 0.01). CONCLUSIONS: In the era of HAART, more patients with HIV infection were admitted to the ICU over a 12-month period than were 10 years previously. Patients were more likely to be injection drug users and were more likely to be admitted to the ICU because of non-HIV-associated conditions.     

Isosporiasis in patients with HIV infection in the highly active antiretroviral therapy era in France

BACKGROUND: Isosporiasis, a rare cause of diarrhoea among HIV-infected patients in the pre-highly active antiretroviral therapy (HAART) era, seems to be re-emerging. METHODS: A retrospective study was carried out for the period 1995-2003 in two hospitals in Paris to describe the prevalence, clinical characteristics and therapeutic outcome of isosporiasis in HIV-infected patients, and to compare the findings with those for cryptosporidiosis and microsporidiosis. RESULTS: The prevalence of isosporiasis increased from 0.4 per 1000 patients in the pre-HAART era (1995-1996) to 4.4 per 1000 patients in the HAART era (2001-2003), whereas the prevalence of cryptosporidiosis and microsporidiosis decreased. Compared with patients with either cryptosporidiosis (n=91) or microsporidiosis (n=58), patients with isosporiasis (n=28) more frequently originated from sub-Saharan Africa (72%), were more frequently female and heterosexual, and had a higher median CD4 count at diagnosis (142 cells/microL). All patients with isosporiasis presented with diarrhoea, which was severe enough to lead to hospital admission for 60% of them. Fever was uncommon (7%). All patients were treated for isosporiasis, 27 of them with cotrimoxazole. Relapse of isosporiasis occurred in six of 16 patients (38%) despite maintenance cotrimoxazole therapy and HAART. CONCLUSION: Isosporiasis in France occurs mostly in patients emigrating from sub-Saharan Africa and can induce severe diarrhoea. Relapse is common despite cotrimoxazole maintenance therapy.     

An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation

Abstract: A 52-year-old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica . Because of the potential fatal course of nocardiosis, transplantectomy was performed and long-term antibiotic treatment was instituted. Three-and-a-half years later, this patient underwent successful re-transplantation under co-trimoxazole prophylaxis. At present, more than 1 year after his second transplant has been performed, there are no signs of recurrence of Nocardia infection. To our knowledge, this is the first report of a patient with nocardiosis with an intrarenal abscess as presenting symptom.     

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation. Thymic transplantation was done without immunosuppression, using postnatal HLA-unmatched cultured allogeneic thymus tissue. Patients were immunized every 6 months with the neoantigen keyhole limpet hemocyanin (KLH) and the recall antigen tetanus toxoid (TT). T cell phenotype and function and T cell receptor rearrangement excision circles (TRECs) were assessed. Thymic allografts were biopsied at 2 months. Six HIV-infected patients completed the study. Four patients received cultured allogeneic postnatal thymic grafts, two others were controls. CD4+ T cell counts increased and T cell-proliferative responses to Candida antigen and TT normalized in all patients. Proliferative responses to KLH developed in three of four transplant recipients and one of two controls. Patients responding to KLH after secondary immunization had greater TREC increases compared with the patients who did not respond. All thymic allografts were rejected within 2 months. In summary, four of six patients developed T cell-proliferative responses to the neoantigen KLH over the first 2 years of HAART. The transplanted thymus tissue, however, was rejected. There was no clear difference in restoration of T cell function in the transplant recipients compared with the controls. Increases in TRECs after initiation of HAART may correlate with improved immune function.     

The eldest of older adults living with HIV: response and adherence to highly active antiretroviral therapy

Objective

The study objective was to analyze the characteristics and the response to therapy in the eldest of the older adults living with human immunodeficiency virus.

Methods

The study included a cohort of patients with human immunodeficiency virus aged 55 years or more on initiating highly active antiretroviral therapy (HAART). Immunologic and virologic response, morbidity, and mortality were assessed. Patients were categorized as aged less than 65 years and 65 years or more.

Results

A total of 112 patients were included (82 patients aged < 65 years and 30 patients aged ≥ 65 years). There were no differences between the age groups in baseline characteristics, survival, and virologic response. There was a trend toward better adherence and a lower CD4+ cell increase after HAART in the older group.

Conclusion

A relationship was found between lower CD4+ cell increase after HAART and advanced age. We found the best adherence to treatment in the eldest of the older adults, and this has been shown to be the only protective independent factor related to virologic failure.     

Immunological response to highly active antiretroviral therapy in children with clinically stable HIV-1 infection

We studied changes in 60 immunological parameters after the administration of highly active antiretroviral therapy (HAART) in 192 clinically stable antiretroviral drug-experienced HIV-1-infected children 4 months-17 years old. The studied immunological parameters included standard lymphocyte subsets and lymphocyte surface markers of maturation and activation. The most significant changes during the 48-week study period were seen for CD8(+), CD8(+)CD62L(+)CD45RA(+), CD8(+)CD38(+)HLA-DR(+), and CD4(+) T cell percentages (P < .0001 for all parameters). These changes suggest that significant decreases in the expression of activation markers and increases in the expression of naive markers in the CD8(+) T cell population may be related to better virologic control in these HIV-1-infected children, who had relatively stable immune function at the initiation of HAART. At week 44 of HAART, the major immunological parameters in these HIV-1-infected children moved from baseline values to about halfway to two-thirds of the way toward the values in healthy, uninfected children.