A prospective study to estimate the incidence and pattern of adverse drug reactions to first-line antiretroviral therapy (tenofovir, efavirenz, and lamivudine).

Background: Antiretroviral drugs are efficacious but are associated with long-term toxicities, drug interactions, and emergence of drug resistance. Objective: To study the incidence and pattern of adverse drug reactions in human immunodeficiency virus (HIV) patients receiving first-line antiretroviral therapy (ART) (tenofovir, efavirenz, and lamivudine (TEL) which was introduced by NACO in 2013. Materials and Methods: A prospective, single-center observational study that included 135 treatment-naive HIV patients who were started on fixed drug once-daily regimen (TEL). At baseline, detailed clinical history, body weight, waist-hip ratio, complete blood count, liver and renal function test, CD4 cell count were performed. Clinical monitoring for cutaneous, neuropsychiatric, and gastrointestinal side effects was done every month along with laboratory monitoring and anthropometric measurement for every 6 months. CD4 counts were measured at baseline and end of the study at 12 months. Results: Out of 135 participants, 89 (65.9%) were males and 46 (34%) were females. The mean age and the mean duration of illness at inclusion were 35.10 ± 8.97 years and 1.2 ± 0.6 years, respectively. The mean increase in weight at baseline and at 12 months (57.55 ± 6.56 to 64.04 ± 8.2) was statistically significant (95% confidence interval [CI]: 4.35-8.62, P < 0.001). The mean CD4 counts at baseline were 309.73 ± 118.44 and increased after 12 months of treatment to 421 ± 129.4 which was statistically significant (95% CI: 81.54-140.99, P < 0.001). The mean difference in platelet count was statistically significant between baseline and 12 months (95% CI: 10.32-46.13, P = 0.002). The mean difference in serum urea levels at baseline and at 6 months (95% CI: 0.60-1.61, P < 0.001) as well as 12 months were statistically significant (95% CI: 0.08-1.03, P = 0.02). The mean increase in serum creatinine at baseline (0.75 ± 0.12) and at 12 months (0.97 ± 0.16) was also significant (95% CI: 0.21-0.28, P < 0.001). There was a significant difference between mean creatinine clearance at baseline and at 12 months (109.9 ± 13.75 to 99.33 ± 12.52, P < 0.0001). One patient discontinued treatment due to adverse effects while two patients were shifted to second-line antiretroviral treatment. Limitations: Small sample size, single-center study and short follow-up period, long-term toxicities were not appreciated. Conclusion: Fixed drug combination with TEL as a first-line ART for HIV is a safe regime as we observed minimal side effects with current regimen.

Identification of clinical and immunological factors associated with clinical relapse of pemphigus vulgaris in remission.

BACKGROUND: Pemphigus vulgaris is a potentially fatal autoimmune epidermal blistering disease with a chronic and relapsing course. It is difficult to predict clinical relapse. Identification of clinical and immunological factors that are associated with early clinical relapse in a prospective study design may help in planning treatment for better maintenance of clinical remission. AIM: The aim of our study was to identify clinical and immunological factors associated with clinical relapse within 9 months of study inclusion in patients with pemphigus vulgaris in clinical remission. METHODS: Forty consecutive consenting patients who had been diagnosed to have pemphigus vulgaris and were in clinical remission on minimal therapy or off therapy were included. The patients were followed up every 3 months until 9 months. Clinical factors considered relevant were recorded at the beginning of the study. Immunological factors such as CD19+ B-cell count and CD19+CD27+ memory B cells/plasma cell count in peripheral blood were assessed at baseline [anti-desmoglein (Dsg) 1 and 3 titers were first assessed at 3 months, not at baseline] and repeated every 3 months, until 9 months or clinical relapse whichever was earlier. Direct immunofluorescence (DIF) of skin biopsy specimen was performed at study initiation and again at the time of clinical relapse or study completion, whichever occurred earlier. All patients completed the study. RESULTS: Of 40 patients, 11 (27.5%) experienced relapse as per definition, while 29 (72.5%) remained in complete remission. Clinical relapse during study duration was significantly more common in those who had onset of disease in oral mucosa [odds ratio (OR), 10.71; 95% confidence interval (CI) 1.21-94.86, P = 0.02], pruritus (OR 8.4; 95% CI 1.76-40.02, P = 0.01), and extensive cutaneous involvement during previous disease activity (OR 7.36; 95% CI 1.34-40.55, P = 0.03) and also pruritus during remission (P = 0.004). Immunological factors found to be significantly associated with early clinical relapse were raised CD19+ B-cell count at baseline (OR 7.84; 95% CI 1.39 - 53.41, P = 0.01), immunoglobulin G (OR 4.85; 95% CI 1.09-23.44, P = 0.04), and C3 (OR 20.33; 95% CI 3.02-199.5, P < 0.001) positivity in the intercellular space of the epidermis on DIF at study onset and rising anti-Dsg 3 antibody titers (OR 19.96; 95% CI 1.85- 310.9, P = 0.03). LIMITATIONS: Limited sample size, short follow-up duration, and inability to perform anti-Dsg enzyme linked immunosorbent assay for all the patients at all the time points of assessment are limitations of this study. CONCLUSION: Immunological relapse can be determined before clinical relapse, so that treatment can be restarted/modified and clinical remission can be maintained.

Nevoid hyperkeratosis of male breast: Successful treatment with minocycline.

Nevoid hyperkeratosis of the nipple and/or areola (NHNA) is an uncommon disease with no definite etiology. NHNA of the male breast is rare in clinical practice. Despite being a benign disease, it is distressing for patients and therapeutically challenging for clinicians. We report a male patient with NHNA who responded favorably to minocycline treatment.