Long-term effectiveness of infrared coagulation for the treatment of anal intraepithelial neoplasia grades 2 and 3 in HIV-infected men and women.

AIMS: To assess the effectiveness and safety of infrared coagulation (IRC) for the ablation of anal intraepithelial neoplasia (AIN) and to provide data on the prevalence of AIN in HIV-infected patients. PATIENTS AND METHODS: We performed a single-center, retrospective cohort study based on data collected from a prospectively compiled database of outpatients attended in the Clinical-Proctology-HIV-Unit (first visit). The effectiveness (normal anal cytology after 12 months of IRC) and safety of IRC were estimated. RESULTS: Between January 2005 and December 2011, a total of 69 (5%) patients with biopsy-proven AIN-2 or AIN-3 from among 1518 patients (1310 men; 208 women) were treated with IRC. The prevalence of cytological abnormalities was 49.5% [751/1518; (atypical squamous cells of unknown significance, 14%; low-grade squamous intraepithelial lesions, 27.5%; high-grade squamous intraepithelial lesions, 8%)]. High-resolution anoscopy revealed intra-anal condylomata in 31% of patients (236/751), nonvisualized lesions in 30% (227/751), and visualized lesions (from which biopsy specimens were taken) in 38% (288/751). The histological diagnosis was: AIN-1, 52% (151/288); AIN-2, 15% (44/288); AIN-3, 9% (25/288); normal, 19% (56/288); and nonevaluable, 4% (12/288). IRC was applied in-office in 66 patients (three refused to undergo treatment). At 12 months, all patients (n = 56) had a normal anal cytology result. Seven (13%) patients had biopsy-proven recurrence [mean (range) time-to-recurrence, 30 (18-43) months]. High-risk-human papilloma virus (HPV) infection was detected in all anal lesions (HPV-16 was the most common genotype). Agreement between cytological and histological results was poor. CONCLUSION: A high prevalence of AIN was found in both HIV-infected men and HIV-infected women. Although randomized clinical trials are lacking, IRC ablation of AIN-2 and AIN-3 lesions without concomitant condylomata could help prevent anal squamous cell carcinoma.

Reversal of HIV-1-associated osteoporosis with once-weekly alendronate.

HIV-1-infected patients with osteoporosis were randomly assigned to alendronate 70 mg once-weekly plus dietary counselling (n = 11) or diet counselling alone (n = 14). At week 96, 27% of patients on alendronate versus 96% of controls presented with osteoporosis. Spine bone mineral density (BMD) increases were detected at week 48, and progressed thereafter. Improvements in trochanter BMD were obtained after 2 years. Once-weekly oral alendronate may be an effective and safe treatment for HIV-1-associated osteoporosis.

Safety and efficacy of once-daily didanosine, tenofovir and nevirapine as a simplification antiretroviral approach.

OBJECTIVE: To assess the efficacy and safety of a once-daily antiretroviral regimen in HAART-experienced subjects with long-lasting viral suppression. METHODS: One-hundred-and-sixty-nine patients with chronically suppressed viral load (limit of detection <50 copies/ml) were recruited. Based on patient willingness to simplify treatment, 84 of them continued receiving their usual treatment (BID Group) and 85 switched to once-daily didanosine/tenofovir/nevirapine (QD Group) in a non-randomized fashion. RESULTS: At week 48, the proportion of patients with viral suppression in the QD and in the BID Group, respectively, was 97 vs 100% in the per-protocol analysis (P = 0.497), and 76 vs 86% for the intention-to-treat analysis (P = 0.176). Nevertheless, CD4 count decreased in the QD Group, with a mean decline of 95 cells/mm3 (95% CI: 45-145). Twelve subjects in the QD Group (14%) discontinued treatment due to adverse events, mainly nevirapine-related hepatitis (6%). No significant differences regarding the rate of acute pancreatitis or peripheral neuropathy were observed between both groups. A significant improvement in the lipid profile was only seen in the QD Group. High levels of adherence were observed in both groups during follow-up, as well as a good quality of life. At week 48, a reduction in effort to take medication (P < or = 0.001) and an increment in the satisfaction with the treatment (P < 0.001) was only seen in the QD group. No differences were observed in median nevirapine trough levels between patients on twice-daily nevirapine at baseline (4820 ng/ml) and subjects in the QD Group (6090 ng/ml, P = 0.30). CONCLUSION: Treatment simplification to a once-daily antiretroviral regimen based on didanosine, tenofovir and nevirapine may be a valid approach in HIV-infected subjects with long-lasting viral suppression. Combination of standard doses of didanosine and tenofovir may have contributed to the CD4 cell decline observed with this QD regimen.

Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.

INTRODUCTION: Alternation of antiretroviral drug regimens has been proposed as a novel treatment strategy for HIV infection. However, some concerns persist regarding antiviral efficacy, adherence, toxicity and resistance evolution in the long term. METHODS: A total of 161 antiretroviral-naive HIV-1-infected patients were randomized to receive stavudine/didanosine/efavirenz (group A) or zidovudine/lamivudine/ nelfinavir (group B) or to alternate between the two regimens every 3 months starting with regimen A (group C). Antiviral efficacy, adherence, safety and tolerability were analysed every 12 weeks. RESULTS: After 96 weeks, time to virological failure was significantly delayed in the alternating regimen compared with the standards of care regimens. Virological suppression was seen in 46%, 48% and 58% of patients in groups A, B and C, respectively, in the intention-to-treat analysis and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014; B vs C: P=0.016; A vs B: P=0.849). At the end of the study, 94% of patients in group A and 92% in groups B and C reported an adherence greater than 95%. Alternating therapy was associated with a similar impact on CD4+ counts in comparison with the standards of care regimens, as well as a lower mitochondrial DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the mitochondrial substudy performed on 37 patients. The frequency and intensity of adverse events in the alternating group decreased during subsequent cycles. DISCUSSION: Our results favour the hypothesis that proactive therapy switching may delay the accumulation of resistance mutations. Moreover, the alternating regimen was well tolerated and adherence remained comparably high in all treatment groups. The lower mtDNA/nDNA ratio decrease observed in this group may imply a lower impact on mitochondrial toxicity than in standard regimens.

Virological, immunological, and clinical impact of switching from protease inhibitors to nevirapine or to efavirenz in patients with human immunodeficiency virus infection and long-lasting viral suppression.

Seventy-seven subjects infected with human immunodeficiency virus were randomized to switch from protease inhibitor (PI) therapy to nevirapine therapy (group A; n=26) or to efavirenz therapy (group B; n=25) or to continue PI therapy (group C; n=26). At month 12, viral suppression had been maintained in 96% of patients in group A, 92% of patients in group B, and 92% of patients in group C. A significant increase in the CD4(+) level was observed in all 3 groups. In group A, lipid profiles improved, whereas levels of gamma-glutamiltransferase and alanine aminotransferase significantly increased; 1 subject interrupted treatment because of hepatotoxicity. In group B, an increase in gamma-glutamiltransferase levels was also observed, and 3 patients interrupted treatment because of central nervous system symptoms. Two patients in group C withdrew therapy. Quality of life significantly improved for groups A and B. In patients receiving effective PI-based therapy, the replacement of the PI with either nevirapine or efavirenz is safe and virologically effective.