Long-acting injectable antiretrovirals for HIV treatment in the ICONA cohort: physicians' and nurses' points of view.

BACKGROUND: Implementation level of long-acting injectable agents cabotegravir/rilpivirine (LAI CAB/RPV) for human immunodeficiency virus (HIV) treatment in Italy is still not known. The aim of this study is to identify the status of implementation of LAI CAB-RPV and its barriers. MATERIALS AND METHODS: A cross-sectional online survey was conducted among infectious diseases (ID) physicians and nurses belonging to the ICONA network in Italy. Three validate 4-items measures were used: Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM) and Feasibility of Intervention Measure (FIM). RESULTS: Out of 61 ICONA centres, 38 (62%) completed the survey: 57.9% were academic centres, 42.1% were hospital-based. In total, 104 respondents were ID physicians (57.4%), 77 were nurses (42.5%); 4.5% of all PWH followed at the 38 centres started LAI CAB/RPV at time of study. Centres taking care of >1000 PWH reported 95% application of procedures for LA implementation, higher than other centres (P = 0.009). Mean score of AIM was (16.0, standard deviation, SD, 3.3), of IAM (16.0, SD 3.0) and FIM (16.0, SD 2.9). A linear correlation was found between AIM and the number of people with HIV who started LAI CAB/RPV (25-50 versus <25, coefficient of correlation [b] 2.57, 95%CI 0.91-4.60, P = 0.004), academic versus hospital-based centres (b -1.59, 95%CI -2.76-0.110044, P = 0.007) and the absence of preliminary systematic assessment of staff (b -1.98, 95%CI -3.31-0.65, P = 0.004). Implementation barriers were not significantly different according to the number of PWH/centre. CONCLUSIONS: LAI CAB/RPV implementation was low, with a great variability according to centre size. Tailored and centre-specific interventions to address barriers and to optimize the LA treatment implementation should be designed.

Virological rebound in human immunodeficiency virus-infected patients with or without residual viraemia: results from an extended follow-up.

Human immunodeficiency virus (HIV) -infected patients with HIV RNA loads of < 50 copies/mL were followed-up for a median (interquartile range) of 30.8 (11.7-32.9) months to study the effect of residual viraemia (RV) on virological rebound (VR). At baseline, 446 (60.3%) patients had undetectable HIV RNA (group A) and 293 (39.7%) had RV (1-49 HIV RNA copies/mL, group B) by kinetic PCR. VR occurred in 4 (0.9%) patients in group A and in 12 (4.1%) patients in group B (p 0.007). Time to VR was shorter among patients of group B (Log-rank test: p 0.003). However, the proportion of VR was extremely low also among patients with RV.

Once-daily saquinavir and ritonavir in treatment-experienced HIV-1-infected individuals.

To assess the efficacy of 48 weeks' treatment with saquinavir 1600 mg and ritonavir 100 mg, both given once daily (SQVOD), in drug-experienced HIV-infected patients, a SQVOD-based therapy was offered to 100 treatment-experienced patients via their own physicians. The patients starting this regimen were followed up for 48 weeks. HIV-RNA was assessed by means of NASBA (limit of quantification = 80 copies/mL). Fifteen patients received the SQVOD-based therapy. Six discontinued before week 48 because of failure, toxicity or intolerance due to the high pill burden and gastrointestinal side effects. The median baseline CD4+ cell counts and plasma HIV-RNA levels were 317 cells/microL (range 44-698) and 4.18 log copies/mL (range 2.65-6.18). At week 4, there was a mean decrease of 1.96 log copies/mL (P < 0.0001) in HIV-RNA, with 75% of the patients having fewer than 400 copies/mL; seven of the nine patients treated for 48 weeks reached fewer than 400 copies/mL. No substantial change in cholesterol or triglyceride values was observed over 48 weeks. As this SQVOD-based regimen had considerable short-term virologic activity in treatment-experienced HIV-infected patients, it may be a reasonable option when non-nucleoside reverse transcriptase inhibitors cannot be administered and once-daily dosing is preferred by the patient. However, the high pill burden and frequent gastrointestinal side effects of the soft gel capsule formulation of saquinavir may limit its long-term efficacy.

The 'cherry buffy-coat syndrome', a cause of decreased platelet yield in platelet concentrates obtained from buffy-coats.

BACKGROUND AND OBJECTIVES: A large number of European blood centres, including our own, use the buffy-coat method for platelet production. In this article we describe a previously unnoticed phenomenon shown by a proportion of buffy-coats, which display an unusually bright cherry colour and low platelet counts. MATERIALS AND METHODS: We performed bacterial cultures, platelet counts, pO2, pCO2 and pH, and evaluated platelet activation by flow cytometry in cherry versus normal-colour (control) buffy-coats. In addition, we compared donor characteristics in the two groups and platelet counts in the packed red blood cells (RBC) obtained from the original donations. Finally, we monitored the frequency of cherry buffy-coats in the bags of three manufacturers, and determined the concordance rate of two trained technicians in detecting cherry buffy-coats. RESULTS: Bacterial cultures were negative. Cherry buffy-coats contained significantly fewer platelets, more O2, less CO2 and had a significantly higher pH than normal buffy coats. Platelet activation was slightly higher in cherry buffy-coats. RBC from donations yielding cherry buffy-coats contained a significantly higher number of platelets than controls. Donor characteristics were not significantly different. Cherry buffy-coats were significantly more frequent with bags from one manufacturer (24%) than from others (9% and 11.6%). The concordance study showed excellent agreement. CONCLUSIONS: Our hypothesis is that the cherry colour is caused by O2 accumulation in buffy-coats with low platelet counts. The latter may be caused by platelet activation and aggregation during blood processing. Further work is needed to determine the cause of this phenomenon, its frequency in different laboratories and means to prevent it.

Lichen myxoedematosus in a patient with AIDS.

We report a patient with acquired immunodeficiency syndrome (AIDS) who developed a widespread papular eruption due to deposition of mucin in the dermis. Paraproteinaemia was demonstrated. Lichen myxoedematosus type 2 was diagnosed. This is the third case of this rare disorder reported in a human immunodeficiency virus (HIV)-seropositive subject.

Intracellular protozoan infection in small intestinal biopsies of patients with AIDS. Light and electron microscopic evaluation.

Small intestinal biopsies of 21 patients with acquired immunodeficiency syndrome (AIDS) with light microscopic findings diagnostic or suspicious for parasite infection were investigated by transmission electron microscopy (TEM). TEM allowed us to identify and specify the genus and species of involved parasites in 16 out of the 21 cases: 7 Cryptosporidium parvum, 5 Enterocytozoon bieneusi and 4 Isospora belli. Cryptosporidium was easily identified on light microscopy (LM), and only slightly influenced by parasite burden in all the 7 cases; TEM confirmed LM diagnosis and made it possible to characterize the parasites as C. parvum. The identification of Microsporidium on LM in our cases was related to the burden of parasite; its presence was certainty identified in 2 cases and suspected in 3. TEM allowed to identify these parasites as E. bieneusi. Intracytoplasmic coccidia could be detected with certainly in semithin sections in all 4 cases, but TEM was always needed to specify the infectious agent as I. belli. In 5 cases the suspicious of protozoan infection on LM (3 microsporidia, 1 intracytoplasmic coccidia and 1 Cryptosporidium) was not confirmed by TEM. Our data suggest that TEM is an appropriate diagnostic tool in this field of pathology and necessary in most of the cases.

Severe abdominal pain in patients with AIDS: frequency, clinical aspects, causes, and outcome.

BACKGROUND: The exact prevalence of abdominal pain in AIDS patients, as well as the entire spectrum of causative disorders, has not yet been well defined. In addition, the existing data derive almost exclusively from surgical series describing only those patients who have undergone emergency surgical procedures. METHODS: We reviewed our experience with patients presenting with severe abdominal pain from a large series of non-selected consecutive AIDS patients seen at our institution over a period of 4 years. RESULTS: Of 458 patients, 71 (15%) had severe abdominal pain, and its occurrence was associated with a reduced patient survival. Specific diagnoses were made premortem in 42 patients (59%), potential causes of pain were identified at postmortem examination in 23 patients (33%), whereas no specific causes were found in 6 patients (8%). Most of the causative disorders (65%) were AIDS-related, whereas HIV-independent pathologic conditions were found in only 18% of the patients. The predominant site of pain, combined with a few key symptoms, had a high predictive diagnostic value in nearly half of the patients. The indications for emergency laparotomy were limited and substantially similar to those of the non-HIV population. CONCLUSIONS: Severe abdominal pain frequently complicates the course of AIDS, and its occurrence is associated with reduced survival. In most patients it is due to disorders closely associated with the HIV infection. Specific causes of pain may be identified in most of the cases by an appropriate diagnostic evaluation.

Prevention of symptomatic recurrences of esophageal candidiasis in AIDS patients after the first episode: a prospective open study.

OBJECTIVES: To evaluate the efficacy and safety of low-dose antifungals as prophylaxis of recurrent esophageal candidiasis after the first episode in patients with AIDS. METHODS: After the first episode of esophageal candidiasis, 122 consecutive AIDS patients were randomly assigned to two different regimens of continuous long-term antifungal prophylaxis (ketoconazole 200 mg or fluconazole 50 mg/day p.o.) or no antifungal therapy over a period of 2 yr. Patients were followed up by monthly clinical controls and upper GI endoscopy in the case of recurrence of esophageal symptoms. RESULTS: One hundred and six patients were clinically evaluable over a mean observation time of 7.5 months. Prophylaxis with oral antifungals significantly reduced symptomatic relapses of esophageal candidiasis, the cumulative probability of relapse at 12 months being 38% in the prophylaxis group, compared with 84% in the untreated group. Both antifungals were sufficiently safe and well tolerated. The clinical response of a second episode of candidiasis to the reintroduction of standard oral antifungals was markedly worse in patients on prophylaxis (especially with ketoconazole) than in untreated patients, presumably due to the development of resistance to the antifungal. CONCLUSIONS: Continuous prophylaxis with both-fluconazole and ketoconazole is effective in preventing recurrences of Candida esophagitis in AIDS patients; however, the possible emergence of strains resistant to these antifungals, as well as the high cost of the therapy, should raise doubts as to whether or not this type of prophylaxis should be extended to all AIDS patients with Candida esophagitis, rather than to limit its use to specific subgroups of patients, such as those with frequent symptomatic relapses.

Non-Hodgkin's lymphoma and AIDS: frequency of gastrointestinal involvement in a large Italian series.

Even though the close association between AIDS and non-Hodgkin's lymphoma (NHL) is widely known, few studies have evaluated the frequency of gastrointestinal involvement in a large series of AIDS patients with heterogeneous risk factors. We therefore reviewed the demographic and clinical features of patients with AIDS and NHL seen at our institution over a period of 5 years. NHLs complicated AIDS in 70 of 786 (9%) cases in our study. All but one of the tumours were of high- or intermediate-grade histologic subtype, and 80% of 56 patients with diagnosis made during lifetime had disease stages III or IV, most with extranodal localization. The gastrointestinal tract was involved in 23 cases (33%), 13 of whom had an antemortem diagnosis. All these patients complained of significant symptoms, the most frequent being GI bleeding followed by recurrent abdominal pain with or without masses. Three patients had evidence of lymphomatous disease along both the upper and lower GI tract, but more often a single localization was present. Prognosis of patients with NHLs was very poor, and there was no significant difference in survival between patients with and without GI localization at the time of initial diagnosis.

Treatment of AIDS-related refractory diarrhoea with octreotide.

We evaluated the effect of octreotide, a long-acting synthetic analogue of native somatostatin, on bowel frequency in 13 patients with AIDS-associated refractory diarrhoea. Cryptosporidium enteritis and cytomegalovirus colitis were the most common causes of diarrhoea. All patients received 100 micrograms t.i.d. octreotide subcutaneously for 1 week; those who did not improve were given 250 micrograms t.i.d. for a further 7 days. Bowel frequency returned to normal in 1 patient, who was affected with cryptosporidiosis, and decreased by more than 50% in 7 others, another patient improved on the higher dose. In 1 case, the beneficial effect disappeared after 10 days of treatment. No major adverse events due to the therapy were observed. We conclude that octreotide has a potential therapeutic use in severe AIDS-related refractory diarrhoea. How to identify patients who may respond remains unknown at present.

Pseudomonas infections in patients with AIDS and AIDS-related complex.

We identified and reviewed retrospectively all the cases of infection by Pseudomonas and related genera in patients with AIDS and AIDS-related complex (ARC) who were hospitalized at our Institution over a 36-month period. We recorded 48 episodes of infection in 34 of 355 patients with AIDS, and in two of 73 patients with ARC: 25 pneumonias (9 community-acquired and 16 of nosocomial origin). 20 urinary tract infections, two soft tissue infections and one sepsis. In 14 of 16 patients with nosocomial pneumonia but in only one of nine patients with community-acquired pneumonia did we find coexisting opportunistic lung diseases. The following micro-organisms were isolated: P. aeruginosa in 41 cases, P. fluorescens in three cases, Xanthomonas maltophilia (P. maltophilia) in two cases, P. putida in one case. Comamonas testosteronis (P. testosteronis) and Comamonas acidovorans (P. acidovorans) in one case. Amikacin and ceftazidime, alone or in combination, appear to be the optimal choice of therapy for severe Pseudomonas infections in HIV-infected patients, although in our study six of 47 isolates were resistant in vitro to amikacin, and nine of 31 isolates were resistant to ceftazidime.

Opportunistic infections of the esophagus not responding to oral systemic antifungals in patients with AIDS: their frequency and treatment.

To determine the spectrum of esophageal disease responsible for dysphagia/odynophagia in AIDS patients not responding to current oral antifungals, we studied 49 consecutive patients whose esophageal symptoms failed to improve after a minimum of 3 wk of therapy with oral ketoconazole or fluconazole. An esophageal candidiasis resistant to oral antifungals was the most frequent disease found (22 single infections and four mixed with viruses). Viral esophagitis was identified in 13 cases (eight herpes simplex virus and five cytomegalovirus), and an esophagitis of unknown origin was documented in two patients. Other causes of symptoms included peptic esophagitis (four cases), esophageal stenosis (two cases), and Kaposi's sarcoma of the esophagus (one patient). Most patients with esophageal opportunistic infection experienced prompt relief of symptoms and complete endoscopic resolution on the specific antifungal (amphotericin B or fluconazole iv) or antiviral (acyclovir or gancyclovir iv) therapy, with the exception of those with concomitant fungal and viral infection who responded poorly to treatment. We conclude that most AIDS patients with dysphagia/odynophagia who do not respond to oral antifungals have an opportunistic infection of the esophagus. Nevertheless, specific antifungal or antiviral therapy is worthwhile, because it will eradicate, at least temporarily, the causative pathogens in most such patients.

Kaposi's sarcoma and AIDS: frequency of gastrointestinal involvement and its effect on survival. A prospective study in a heterogeneous population.

The frequency and distribution of gastrointestinal Kaposi's sarcoma were prospectively investigated in 33 consecutive AIDS patients with heterogeneous risk factors and established skin or lymph-node disease. The influence of visceral involvement and degree of immunosuppression at the time of diagnosis on patient survival was also evaluated. Gastrointestinal lesions were found in 17 cases (51%): 5 patients (15%) had both upper and lower GI tract involvement, 8 patients (24%) had only gastroduodenal lesions, and 4 (12%) only lower tract disease. No difference in the frequency of visceral involvement was found between the two major risk groups (homosexuals and intravenous drug abusers). The degree of immunosuppression at diagnosis was the major determinant of survival, whereas gastrointestinal involvement did not in itself significantly influence patient survival. Morbidity from enteric Kaposi's sarcoma was quite low, 80% of these lesions being clinically silent during the follow-up period.

Acute upper gastrointestinal bleeding in patients with AIDS: a relatively uncommon condition associated with reduced survival.

To determine the cumulative incidence of acute upper gastrointestinal bleeding and its effect upon survival in patients with AIDS, 453 consecutive AIDS patients diagnosed in our hospital between June 1985 and March 1989 were followed for a median period of six months (maximum 42 months). The cumulative probability of acute gastrointestinal bleeding was 3% at six months and 6% at 14 months. This event was associated with significantly reduced survival. Independent risk factors for bleeding were: severe thrombocytopenia at the time of diagnosis and non-Hodgkin's lymphoma as the first clinical manifestation of AIDS. The potential causes of bleeding were investigated in all cases by emergency endoscopy or by necropsy examination in those patients whose clinical condition precluded the procedure. In nine of 15 patients, bleeding was due to lesions specifically associated with AIDS, but in the remainder the source of bleeding was not a direct consequence of HIV infection. We conclude that acute upper gastrointestinal bleeding rarely complicates the course of AIDS, but its occurrence is associated with decreased survival. As many of the causes are potentially treatable, a complete diagnostic approach is indicated in these patients, except those who are terminally ill.