The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

OBJECTIVES: Electrocautery is one of the main treatment options for high-grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN. METHODS: An observational study of HIV-infected men who have sex with men (MSM) who underwent screening for anal dysplasia was carried out. The on-treatment effectiveness of electrocautery was evaluated (according to biopsy findings measured 6-8 weeks after treatment) in patients with HGAIN. A complete response was defined as resolution of anal intraepithelial neoplasia (AIN), a partial response as regression to low-grade AIN and recurrence as biopsy-proven HGAIN during follow-up. RESULTS: From May 2009 to November 2014, 21.9% (126 of 576) of patients screened were found to have HGAIN. Electrocautery effectiveness was evaluated in 83 patients. A complete response was observed in 27 patients [32.5%; 95% confidence interval (CI) 23.4-53.2%], a partial response in 28 patients (33.7%; 95% CI 24.5-44.4%) and persistence in 28 patients (33.7%; 95% CI 24.5-44.4%). The patients with the most successful results (81.8%) required two to four sessions of electrocautery. After a mean follow-up of 12.1 months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9 months (95% CI 22-37.7 months). No patient progressed to invasive cancer during the study or developed serious adverse events after treatment. No factors associated with poor response or recurrences were observed. CONCLUSIONS: Although electrocautery is the standard treatment for anal dysplasia, almost 50% of patients with HGAIN in our study did not respond or relapsed. New treatment strategies are necessary to optimize the management of anal dysplasia.

Outcome of neuropsychiatric symptoms related to an antiretroviral drug following its substitution by nevirapine: the RELAX study.

OBJECTIVES: The primary objective was to evaluate the improvement in neuropsychiatric symptoms attributed to an antiretroviral drug after that drug was substituted with nevirapine. The secondary objective was to evaluate the impact on patient adherence and quality of life. METHODS: A prospective, observational study was carried out that included patients with HIV-1 plasma suppression for whom an antiretroviral drug was substituted with nevirapine because of central nervous system (CNS) side effects, a Pittsburgh Sleep Quality Index (PSQI) score > 5 or a Hospital Anxiety and Depression Scale (HADS) score ≥ 10, and who had not initiated psychoactive drug treatment during the prior 6 weeks. Evaluations were carried out at baseline and 1 and 3 months after the switch using the PSQI, HADS, Epworth Sleepiness Scale, Medical Outcomes Study-Short Form 30 items (MOS-SF-30) and Simplified Medication Adherence Questionnaire (SMAQ). RESULTS: A total of 129 patients were included in the study. The drug substituted was mainly efavirenz (89.9%), and reasons for the switch included sleep disturbances (75.2%), anxiety (65.1%), depression (38.7%), attention disturbances (31%), and other reasons (31%), with a mean of 2.4 neuropsychiatric disturbances per patient. A statistically significant improvement was observed in all the tests evaluating neuropsychiatric symptoms and adherence at 1 and 3 months. The CD4 lymphocyte count remained stable (P = 0.096). Three (2.3%) patients had a detectable plasma HIV-1 RNA at the end of the study. Nine patients (6.9%) withdrew because of nevirapine-related toxicity (rash in seven patients and hypertransaminasaemia in two patients, none of which were > grade 2). CONCLUSIONS: The switch to nevirapine from a drug causing neuropsychiatric disturbances (primarily efavirenz) in subjects with virological suppression was effective in resolving those disturbances, with an improvement in all the parameters studied. This led to better adherence to treatment and quality of life, with no detrimental effect on their immunological and virological control.

Impact of the COVID-19 pandemic: Community and hospital shared pharmaceutical care model. Satisfaction and acceptability of patients with HIV infection on antiretroviral treatment.

OBJECTIVE: The health crisis due to the COVID-19 pandemic is a challenge in the dispensing of outpatient hospital medication (OHM). Models of Antiretroviral Therapy (ART) based on community pharmacy support (ARTCP) have proven to be successful. The aim was to evaluate the degree of satisfaction, acceptability and limitations of the implementation of ARTCP, in the context of a pandemic, in our environment. METHODS: Descriptive cross-sectional study carried out in a Barcelona hospital, during the months of July-November 2020. A telephone survey was carried out via a questionnaire on the quality dimensions of the model (degree of satisfaction, acceptability) and associated inconveniences. Data collected: demographics, antiretroviral treatment (ART), concomitant medication, drug interactions (DDIs), CD4 lymphocyte count and plasma viraemia. Data analysis included descriptive statistics. RESULTS: A total of 533 (78.0%) HIV patients receiving ART were included. 71.9% (383/533) of these patients were very satisfied and 76.2% preferred attending the community pharmacy rather than the hospital. The mean satisfaction rating was 9.3 (DS: 1.4). The benefits reported were: 1) proximity to home (406: 76.1%); 2) lower risk of contagion of COVID-19 (318: 59.7%); 3) shorter waiting time (201: 37.1%); 4) time flexibility (104: 19.5%); 5) reduction of financial expenses (35: 6.57%). A total of 11 (2%) patients reported no benefit. Only 22.9% reported disadvantages associated with ARTCP: 1) lack of privacy (65: 12.2%); 2) lack of coordinationorganization (57: 10.7%). CONCLUSIONS: The COVID-19 pandemic has had an impact on the provision of pharmaceutical care for HIV patients. The ARTPC model has proved efficient, with patients reporting a high degree of satisfaction.

Use of non-nucleoside analogues together with rifampin in HIV patients with tuberculosis.

OBJECTIVE: The concomitant use of rifampin (RFP) with efavirenz (EFV) or nevirapine (NVP) is frequent in HIV patients with tuberculosis (TB). The necessity of increasing the dose of EFV remains controversial. The aim of the study was to evaluate the outcome of HIV infection in patients treated with non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) and RFR. METHODS: Retrospective analysis of HIV patients who were simultaneously treated with RFP and NVP or EFV. The dose of EFV was considered to be adjusted in those patients receiving 600 mg when weighing <60 kg and 800 mg if >60 kg and was considered nonadjusted when the dose given was 600 mg in patients >60 kg. RESULTS: 63 patients were included: 13 received NVP and 50 received EFV-based ART (30 adjusted and 20 nonadjusted). Treatment failure was observed in 7 (53.8%) of the NVP group; 11 (55%) of the nonadjusted EFV group, and 8 (26.7%) of the adjusted EFV group (P = .04). The relative risk (RR) of treatment failure comparing nonadjusted and adjusted EFV was 3.36 (95% Cl, 1.02-11.11). The proportion of treatment failure was 9/18 (50%) in the nonadjusted and 5/27(18.5%) in the adjusted EFV group. CONCLUSIONS: The effectiveness of NVP and nonadjusted EFV was lower than adjusted EFV-based ART. It may be advisable to increase the dose of EFV to 800 mg once daily when administered with rifampin in patients weighing >60 kg.

Impact of different patterns of nonadherence on the outcome of highly active antiretroviral therapy in patients with long-term follow-up.

OBJECTIVES: The aim of the study was to evaluate the impact of different patterns of nonadherence on treatment outcomes in patients with long-term follow-up. METHODS: This cohort study included patients who began highly active antiretroviral therapy during 1996-1999, with the last follow-up in 2007. Adherence was evaluated every 2 months by monitoring of pharmacy refills and by using self-reports. Patients were considered nonadherent at a specific visit when less than 90% of the prescribed drugs had been taken. Adherence was categorized as follows. (A) Continuous adherence: a patient had to be adherent in all of the evaluations throughout the period of follow-up. (B) Treatment interruption: drugs were not taken for more than 3 days, for any reason. Treatment failure was defined as viral load >500 HIV-1 RNA copies/mL or death. Cox proportional risk models were used to calculate adjusted relative hazards (ARHs) of treatment failure. RESULTS: A total of 540 patients were included in the study, with a median follow-up of 8.3 years. Only 32.78% of patients achieved and maintained continuous adherence, and 42.78% of patients had treatment interruptions. Noncontinuous adherence [ARH 1.48; 95% confidence interval (CI) 1.02-2.14] and treatment interruptions (ARH 1.39; 95% CI 1.04-1.85) were associated with treatment failure for the overall cohort; however, for patients with more than 3 years of follow-up, only treatment interruptions were independently associated with treatment failure. CONCLUSIONS: Only one-third of patients managed to achieve continuous adherence, and almost half of the patients had treatment interruptions, which have a particularly marked effect on treatment outcomes over the long term.

Frequency and severity of potential drug interactions in a cohort of HIV-infected patients Identified through a Multidisciplinary team.

OBJECTIVES: Interactions between antiretroviral treatment (ART) and comedications are a concern in HIV-infected patients. This study aimed to determine the frequency and severity of potential drug-drug interactions (PDDIs) with ART in our setting. METHODS: Observational study by a multidisciplinary team in 1259 consecutive HIV patients (March 2015-September 2016). Data on demographics, toxic habits, comorbidities, and current ART were collected. A structured questionnaire recorded concomitant medications (including occasional and over-the-counter drugs). PDDIs were classified into four categories: (1) no interactions, (2) mild (clinically non-significant), (3) moderate (requiring close monitoring or drug modification/dose adjustment), and (4) severe (contraindicated). STATISTICAL ANALYSIS: chi-square test, logistic regression analysis. RESULTS: In total, 881 (70%) patients took comedication, and 563 (44.7%) had ≥ PDDI. Forty-one comedicated patients (4.6%) had severe and 522 (59.2%) moderate PDDIs. Moderate PDDIs mainly involved cardiovascular (53.8%) and central nervous system (40.2%) drugs. Independent risk factors for PDDIs were ART containing a boosted protease inhibitor (odds ratio [OR]=9.11, 95% confidence interval [CI] 5.15-16.11; p = 0.0001) and/or non-nucleoside reverse transcriptase (NNRTI) (OR = 4.34, 95%CI 2.49-7.55; p = 0.0001), HCV co-infection (OR = 3.26, 95%CI 2.15-4.93; p = 0.0001), and use of two or more comedications (OR = 3.36, 95%CI 2.27-4.97; p = 0.0001). Adherence and effectiveness of ART were similar in patients with and without PDDIs. The team made 133 recommendations related to comedications (drug change or dose adjustment) or ART (drug switch or change in administration schedule). CONCLUSIONS: Systematic evaluation detected a significant percentage of PDDIs requiring an intervention in HIV patients on ART. Monitoring and advice about drug-drug interactions should be part of routine practice.

A prospective study of the risk of tuberculosis among HIV-infected patients.

OBJECTIVE: To evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. METHODS: Prospective longitudinal follow-up of 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration > or = 5 mm). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. RESULTS: Active TB developed in 23 out of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test but a positive Multitest developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and nine who converted during follow-up). Active TB developed in seven out of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in four out of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +/- 103 x 10(6)/l (range, 1-400 x 10(6)/l). CONCLUSIONS: Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

PIP: This study sought to evaluate the risk of developing active tuberculosis (TB) in a cohort of HIV-1-infected patients. A prospective longitudinal follow-up was carried out on 839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269 (32%) were homosexual men. Tuberculin skin tests were performed at baseline and annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was offered to those with a positive tuberculin test (induration or= 5 mm.). Diagnosis of TB was accepted if it could be confirmed microbiologically (acid-fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures) or pathologically (presence of caseating granulomas) and patients had consistent clinical manifestations. Active TB developed in 23 of the 733 (3.1%) patients with a negative tuberculin skin test after a mean follow-up of 16 +or- 11 months (range, 2-52 months), with an estimated cumulative probability of 1.5 and 7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the 87 patients with a negative tuberculin test, but a positive Multitest, developed TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline and 9 who converted during follow-up). Active TB developed in 7 of the 26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2 per 100 patient-years), in 4 of 61 patients 3-27 months after having completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years), and in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4 lymphocyte count of the 34 patients who developed it during follow-up was 77 +or- 103 x 106/L (range, 1-400 x 106/L). Among HIV-infected patients in whom the tuberculin skin test is negative, the risk of developing active TB is sufficient to consider prophylaxis if the CD4 count falls below 400 x 106/L, at least in those patients with skin anergy living in high-risk geographical areas such as Spain. When the tuberculin skin test was positive, isoniazid (9 months) provided a 45% protection beyond the period of its administration.

Hyperperfusion and early technetium-99m-HMPAO SPECT appearance of central nervous system toxoplasmosis.

Three correlative 99mTc-HMPAO brain SPECT studies were performed on an AIDS patient from the early stage of a CNS toxoplasma lesion to its resolution after specific therapy. A hyperactive area in the right parieto-occipital lobe appeared in the first SPECT study, matching the heterogeneous T2-weighted image with Gd-DTPA enhancement reported on MRI. Both studies were performed 3 days after the onset of neurological symptoms when no abnormalities were found on a CT scan. This fact can be explained by the hyperemia that occurs in the acute stage of inflammation. Three months later, along with clinical improvement under specific treatment, both MRI and brain SPECT were normal. No hypoperfusion was seen in SPECT images, probably because the necrotic phase of the toxoplasma lesion was not reached in this case.

Subglottic stenosis in an HIV positive patient: an exceptional form of clinical presentation in Kaposi's sarcoma.

The case of a 29-year-old HIV positive male patient suffering from a Kaposi's sarcoma exclusively located in the proximal third of the trachea and subglottic region is presented. The patient was found to have included an obstruction of the upper airway. A characteristic endoscopic appearance led to the final diagnosis. A combined treatment with Nd-YAG laser endoscopic resection and laringotracheal irradiation was performed. Pathological examination confirmed Kaposi's sarcoma.

Virologic outcome and predictors of virologic failure of highly active antiretroviral therapy containing protease inhibitors.

In this observational single-center cohort study outside the clinical trial setting, outcome and predictors of virologic failure of highly active antiretroviral therapy (HAART) containing a protease inhibitor were evaluated in human immunodeficiency (HIV)-infected persons. The study population consisted of 807 protease inhibitor-naive HIV-seropositive patients who initiated antiretroviral therapy with reverse transcriptase inhibitors and protease inhibitors (indinavir, nelfinavir, ritonavir) between January 1997 and January 1999. Demographic variable, plasma HIV-1 RNA levels, CD4+ T-cell count, adverse drug reactions, and adherence to HAART were assessed. Virologic treatment response was defined as a decrease in plasma HIV-1 RNA load from baseline to below 500 copies per milliliter after 12 months of therapy. Levels of HIV-1 RNA were undetectable in 43% of patients at 12 months. Factors associated with failure to suppress viral load included age 40 years or younger, baseline CD4+ T cell count less than 200 x 10(6) per liter baseline viral load greater than 4.3 log(10) per milliliter, and non-adherence to HAART. After adjustment by logistic regression, non-adherence was the only statistically significant variable associated with virologic failure (odds ratio 0.38, 95% confidence interval 0.21 to 0.67). Unselected patients in whom protease inhibitor is started in a usual clinical setting achieve viral suppression less frequently than do patients in controlled clinical trials. Failure to adherence to HAART was the strongest predictor of virologic failure.

[Encephalic toxoplasmosis in patients with the acquired immunodeficiency syndrome. A clinico-radiological study and the therapeutic results in 78 cases]. / Toxoplasmosis encefálica en pacientes con síndrome de inmunodeficiencia adquirida. Estudio clínico-radiológico y resultados terapéuticos de 78 episodios.

During a 40-month period 78 episodes of encephalic toxoplasmosis (ET) were diagnosed in 57 patients among 394 with acquired immunodeficiency syndrome (AIDS) (based on CDC criteria) in the Hospital Clinic from Barcelona. 38 patients were parenteral drug abusers (66.7%), 17 were homosexual males (29.8%) and 2 were heterosexual females (3.5%). ET was the first opportunistic infection in 28 patients (49.1%). The most common symptoms at the time of diagnosis were focal neurological signs (62.8%) and fever (52.6%). Usually, computed tomography showed single or multiple hypodense lesions (70.3%) with ring-like (46.1%) or nodular (28.3%) uptake. Serology (indirect immunofluorescence) was diagnostic in only 24 cases (42.1%). The acute episodes were treated with the combination pyrimethamine/sulfadiazine (P/S) during 3-6 weeks, and folinic acid was associated. If the patient had previous allergy to sulfonamides or allergy developed during the acute phase, clindamycin (C) was given instead of S. The patients surviving the acute episode (49, 86, 0%) underwent, if they consented, maintenance therapy with P/S two days per week (15 patients) or with C if sulfonamide allergy was present (10 patients). No relapse was observed in those receiving P/S, but 40% of those treated with P/C relapsed. It was concluded that ET is a common opportunistic infection in the AIDS patients, that the treatment of the acute phase with P/S or with P/C is satisfactory, and that maintenance therapy with P/S two days per week may be effective to prevent relapses.

Risk of side effects associated with the use of nevirapine in treatment-naïve patients, with respect to gender and CD4 cell count.

OBJECTIVES: A warning about the use of nevirapine (NVP) by its pharmaceutical manufacturer has been issued in which it has been recommended that NVP should not be prescribed in patients with increased risk of toxicity based on CD4 cut-offs and gender. The aim of this study was to determine whether these recommendations are of use in preventing side effects. METHODS: This retrospective study included antiretroviral drug-naïve patients who started treatment with NVP. Patients were divided into two groups: those with high CD4 counts (H; women: CD4 count >250 cells/microL; men: CD4 count >400 cells/microL) and those with low CD4 counts (L; women: CD4 count <250 cells/microL; men: CD4 count <400 cells/microL). RESULTS: A total of 142 patients were included in the study, 61 in the H group and 81 in the L group. Skin rash developed in 6.56% of patients [95% confidence interval (CI) 2.67-15.70%] in the H group and in 14.81% of patients (95% CI 8.72-24.17%) in the L group (P=0.18). Hepatotoxicity developed in 4.92% (95% CI 1.79-13.50%) and 6.17% (95% CI 2.73-13.66%) of patients with high and low CD4 cell counts, respectively (P=1.0). CONCLUSION: The recommendations not to use NVP in drug-naïve patients at increased risk of toxicity on the basis of gender and CD4 cell count do not seem to be of use in preventing the occurrence of side effects. However, a small number of patients were included in this study, and hence the possibility cannot be excluded that the recommendations are appropriate in another clinical practice setting.

Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir-boosted saquinavir. The CIVSA Study.

BACKGROUND: The addition of a low dose of ritonavir to protease inhibitors (PIs) has become a widespread strategy to improve PI pharmacokinetics. As resistance is a major barrier to long-term suppression, in salvage therapy genotype and/or phenotype scoring is currently used to predict the response. We evaluated the relationship between the saquinavir (SQV) inhibitory quotient (IQ) (virtual and genotypic) and virological response. METHODS: Eligible patients were on a PI-containing highly active antiretroviral therapy (HAART) regimen excluding SQV and had a viral load >5000 HIV-1 RNA copies/mL. The PI was switched to SQV/ritonavir (RTV) 1000/100 mg twice a day (bid) and the same two backbone nucleoside reverse transcriptase inhibitors (NRTIs) were maintained at least until week 4, when the resistance test results became available. Genotype and virtual phenotype were determined at baseline, while the SQV trough plasma concentration was determined at week 4. RESULTS: Fifty-three patients were included in the study. Mean baseline viral load and CD4 count were 137,693 copies/mL and 263 cells/microL, respectively, the mean number of previous PIs was 2.3 and the mean number of protease gene mutations (PGMs) was 4.1. Using an on-treatment analysis, at week 16 the mean increase in CD4 count was 70.9 cells/microL, viral load was <200 copies/mL in 17 out of 37 patients (45.9%), and 30 out of 45 patients (66.7%) were considered virological responders (VRs) (viral load <200 copies/mL or viral load declined > or =1 log(10) at week 16). Median virtual phenotype was 1.3 (0.6-6.9). Baseline differences were detected between VR and non-VR populations: the mean numbers of PGMs were 3.2 and 5.8 (P<0.05), the mean numbers of SQV-associated mutations were 2 and 3.8 (P<0.05), and the mean CD4 counts were 365.9 and 184.3 cells/microL (P<0.05), respectively. Mean SQV trough concentrations at week 4 were 1.1 and 1.0 microg/mL (not significant), and mean virtual IQs were 0.7 and 0.1 (P<0.01), respectively. Multivariate analysis showed that baseline PGMs >5 or SQV-associated mutations>5, virtual phenotype, baseline viral load >50,000 copies/mL, and virtual IQ <0.5, but not genotypic IQ, were the variables independently associated with non-VR. CONCLUSION: In heavily pretreated patients, the use of SQV virtual IQ or alternatively virtual phenotype, as well as PGMs, is a useful tool for the prediction of virological response.