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Background: Although many drug regimens have been used in the treatment of human immunodeficiency virus (HIV) infection, the National AIDS Control Organization (NACO) of India recommends the use of a fixed-dose combination of tenofovir/lamivudine/dolutegravir (TLD) as a first-line regimen since 2020. In spite of much global data on the use of this combination, experience in the Indian population is still limited. We aim to find out the efficacy and tolerability of this novel regimen, in a tertiary care center of Eastern India., Materials and Methods: A descriptive observational study, longitudinal in design performed in the antiretroviral therapy (ART) center of a tertiary care hospital in Kolkata, West Bengal, India. All patients who attended the ART center from April 2021 to October 2022 were enrolled in the study following inclusion and exclusion criteria. A detailed history, clinical examination, necessary biochemical tests, and CD4 count of all patients were done at baseline. Subsequently, they were followed up for 6 months with monthly visits when they were enquired about any adverse effects requiring therapy interruptions. At the end of 6 months, CD4 count and viral load were measured., Results: Out of a total sample of 249 patients, the TLD regimen was efficacious in 99.2% ( n = 247) in whom viral load was suppressed to <1,000 copies/mL after 6 months of treatment. The regimen had to be temporarily discontinued in 6% of patients ( n = 15). The most common cause of treatment interruption was hepatic dysfunction (3.2%) followed by cutaneous manifestation (2.4%). In 14 out of 15 patients, the regimen could be reintroduced and was safely tolerated afterward. Only one patient had to be shifted to an alternative regimen due to tenofovir-induced nephrotoxicity. Thus TLD was tolerated in 99.6% ( n = 248) patients., Conclusion: The fixed-dose combination of TLD is a highly efficacious and well-tolerated first-line regimen for ART naïve patients with HIV infection having >95% adherence. How to cite this article: Sengupta D, Ghosh S, Pain S, et al. Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India. J Assoc Physicians India 2023;71(9):72-74., (© Journal of the Association of Physicians of India 2023.)

Objectives: As per National AIDS Control Organization (NACO) estimates, there are 2.1 million people living with HIV (PWH) in India, of whom 1.2 million are on first-line antiretroviral therapy (ART). This study explored the use of a single-tablet regimen containing tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg + efavirenz 400 mg (TLE400 STR) as a first-line switch strategy in PWH in Pune, India., Methods: This retrospective cohort study was conducted in private sector ART clinics in three tertiary-level hospitals in Pune, India. PWH > 12 years of age (n = 502) who initiated first-line ART (predominantly TLE600 STR), completed ≥ 6 months of follow-up and achieved virological suppression [plasma viral load (VL) < 1000 HIV-1 RNA copies/mL] were identified and switched to TLE400 STR. The virological and immunological efficacy of TLE400 STR at 6 and 12 months of follow-up were noted. Grade 3/4 adverse events (especially efavirenz-related neuropsychiatric adverse events) leading to regimen discontinuation were also noted., Results: Of 502 PWH who switched to TLE400 STR, complete virological suppression (VL < 20 copies/mL) was maintained in more than 97% of patients at follow-up. TLE400 STR was successful in maintaining CD4 counts within the range observed at the start of the regimen. Grade 3/4 adverse events leading to TLE400 STR discontinuation were seen in 11 (2.2%) patients. Virological failure (VL > 1000 copies/mL) and treatment regimen failure were seen in six (1.2%) and 49 (9.8%) subjects, respectively., Conclusions: TLE400 STR exhibits excellent efficacy and safety as a switch strategy and should be introduced in the Indian National ART Program, especially for PWH who are virologically suppressed on TLE600 STR., (© 2020 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

A 58-year-old, nonalcoholic, nonsmoker, official in private enterprise presented with a confirmed case of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and an itchy, violaceous skin eruption over the lower part of the left leg. He noticed a change in the color and texture of the skin for the first time 2 years ago. Ever since that time, the eruptions had insidiously progressed. He was started on highly active antiretroviral therapy (HAART), comprising 600 mg of zidovudine, 300 mg of lamivudine, and 600 mg of efavirenz for the past year. Despite the therapy, the lesions continued to progress. He claimed to be very compliant with therapy. In addition, he developed pulmonary tuberculosis during the course of the disease. Accordingly, he was treated with a daily schedule' of antitubercular therapy, comprising 450 mg of rifampicin, 300 mg of isoniazid, 1500 mg of pyrazinamide, and 800 mg of ethambutol for 9 months. He experienced a significant loss of weight and appetite. The patient was a divorcee but refused to divulge any details of his married life after a considerate and focused discussion by a trained counselor on HIV/AIDS. He emphatically denied any extramarital sexual contact, blood transfusion, and surgery in the past. Ultimately, the patient's disease status was defined by HIV viral load (< 20 copy/mL) after obtaining informed consent.

There is limited information on the prevalence and pattern of HIV drug-resistant mutations (DRMs) among HIV-1-coinfected tuberculosis (TB) patients before and after antiretroviral treatment. Patients with HIV-1 and TB were recruited into a clinical trial from two different once-daily antiretroviral regimens and followed for a period of 6 months after ART initiation. Patients were treated with standard short-course anti-TB treatment (2EHRZ3/4RH3) and were randomized to receive ddI/3TC with either nevirapine or efavirenz, once daily. Genotypic drug resistance (DR) testing was carried out for the pol gene at baseline and at the time of virological failure. At baseline, major DRMs with respect to NNRTIs (G190GA) and TAMs (T215S and I) were observed in 3 out of 107 patients. Of 15 treatment failures, 14 had more than one major NRTI and NNRTI mutation. V106M was the major NNRTI mutation that emerged in EFZ and Y181C in the NVP group. Among NRTI mutations, M184V was the commonest followed by L74I/V. Primary drug resistance to antiretroviral drugs was low among HIV-1 co-infected TB patients in south India. A once-daily regimen of ddI/3TC/EFZ or NVP results in a specific pattern of NNRTI mutations and negligible thymidine analog mutations (TAMs).

Background: The clinical efficacy of highly active antiretroviral therapy (HAART) in children has been well documented in the developed countries, although most of the regimens are Protease Inhibitor (PI) based which are too expensive. To circumvent this problem World Health Organization (WHO) has recommended Non- Nucleotide Reverse Transcriptase Inhibitor (NNRTI) based regimen for resource-limited countries., Aim: To assess the long-term efficacy of first line World Health Organization (WHO)-recommended generic highly active antiretroviral therapy (HAART) regimens in treatment -naïve children., Materials and Methods: Observational retrospective analysis was done. Thirty patients on HAART for >or= 6 months were included (27 on Stavudine; three on Zidovudine with Lamivudine/ Nevirapine). No protease inhibitors were used., Results: Median age was seven years (Interquartile [IQR]: 5.62-8.50) and median duration on HAART was 18 months (IQR: 6-24). No new staging events were observed after six months of initiation of HAART. The median CD4% increased from 6.0 % at baseline to 15.5% at six months, 21.7% at 12 months, 25.4% at 18 months, 24.6 % at 24 months 25.3% at 30 months and 23.7% at 36 months. There was only one case of immunological failure. Stratifi ed analysis based on baseline CD4% show that even patients with a baseline CD4 % of <5% achieved percentage of >25% at 18-24 months and maintained it subsequently. Significant increase in the weight and body mass index Z scores was observed but significant fall in the height Z scores were observed. This sub group of patients with poor linear height velocity would require detailed endocrine evaluation after testing for viral loads., Conclusions: Non- Nucleotide Reverse Transcriptase Inhibitor based HAART regimens are feasible and effective in long term in resource-limited setting despite initiation of treatment in advanced stages. These can be continued in NACO/WHO scale up programmes at present for children.

Background: Because of the lack of suitable pediatric antiretroviral (ARV) agents, adult fixed-dose ARVs are commonly used in children. This practice poses concerns about dose inaccuracy, which may lead to resistance or toxicity., Objective: The objective of the present study was to evaluate the bioequivalence of a new pediatric fixed-dose combination (FDC) ARV tablet for oral suspension as compared with individual liquid formulations., Methods: The FDC ARV tablet for oral suspension contained lamivudine 40 mg, nevirapine 70 mg, and stavudine 10 mg. This formulation was compared with 4 mL of lamivudine 10 mg/mL, 7 mL of nevirapine 50 mg/5 mL, and 10 mL of stavudine 1 mg/mL. This was an open-label, balanced, randomized, 2-treatment, 2-period, 2-sequence, single-dose crossover study in 36 Indian male volunteers under fasting conditions. Blood samples were collected before dosing and at 0.167, 0.25, 0.333, 0.5, 0.667, 0.833, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, and 192 hours after dosing in each period., Results: The mean (SD) age, weight, and height of the Indian volunteers were 24.78 (5.31) years (range, 18-38 years), 57.06 (8.59) kg (range, 45-77 kg), and 165.14 (5.34) cm (range, 156-176 cm), respectively. The mean (SD) values for T(max), C(max), and AUC(0-t) for the FDC and the individual liquid formulations, respectively, were as follows: lamivudine, 0.71 (0.22) and 0.89 (0.50) hour, 594 (167) and 514 (139) ng/mL, 2382 (617) and 2227 (666) ng /mL per hour; nevirapine, 1.7 (1.1) and 2.5 (1.2) hours, 1248 (275) and 1185 (238) ng/mL, 70,372 (14,869) and 71,278 (17,435) ng/ mL per hour; and stavudine, 0.44 (0.11) and 0.43 (0.11) hour, 348 (82) and 395 (107) ng/mL, and 576 (113) and 631 (142) ng/mL per hour. The ratios and 90% CIs for the least-squares mean Cmax and AUC values were found to be within the prespecified range of 80% to 125% for each component., Conclusion: The FDC pediatric formulation of lamivudine, nevirapine, and stavudine was bioequivalent to the individual liquid formulations in these fasting, healthy Indian men.

Background: There is a paucity of reports on Highly Active Antiretroviral therapy (HAART) in children. We studied feasibility and effectiveness fixed dose combination (FDC) of lamivudine, nevirapine and stavudine in HIV infected children., Design: Interventional study., Setting: A Tertiary care center., Subjects: Twenty five consecutive HIV positive antiretroviral naive children older than 18 months., Methods: The study subjects were started on weight-appropriate doses of the FDC and followed up for 6 months. Weight, CD4 counts, absolute lymphocyte count (ALC) and number of episodes of illness were assessed before and after HAART. Adherence and barriers to adherence were studied., Results: Mean weight increased from 15.2 to 16.8 kg (P < 0.001) while mean CD4 counts increased from 488/cmm to 765/cmm (P < 0.001). Only 2 cases of drug associated adverse event were encountered. Improvement in Center for Disease Control (CDC) immunological classification of the subjects was significant while that in World Health Organization (WHO) clinical staging was not statistically significant. Follow up visits were 95% of the expected 175 visits. The average distance traveled by the patient for every visit was 72 km (one way)., Conclusions: Use of FDC in weight specific dosages is feasible and effective for treatment of Pediatric HIV in resource scarce setting. These preliminary results need to be tested in a different setting.

Low-cost generic antiretroviral drugs are available in resource-limited settings for treatment of HIV infections. However, few bioequivalence data in specific populations in which these generics are likely to be used are available. We conducted a randomized crossover bioequivalence study of generic and brand name formulations of nevirapine, zidovudine, and lamivudine in HIV-negative Indian women using US Food and Drug Administration (FDA) criteria. Subjects took single doses of all formulations separated by a 14-day washout period. Plasma concentrations were measured over 96 hours during each study period. Average bioequivalence was determined using natural log-transformed maximum concentration (C(max)) and area-under-the-concentration-time curve (AUC) mean ratio data. Fifteen Indian women were enrolled. The 90% confidence intervals for nevirapine (14 subjects) and lamivudine (15 subjects) C(max), AUC from 0 to the last measurable time point (AUC(0-t)), and AUC from 0 to infinity (AUC(0-infinity)) mean ratios and zidovudine (15 subjects) AUC(0-t) and AUC(0-infinity) mean ratios were all within 0.80 to 1.25. However, the 90% confidence interval for zidovudine C(max) mean ratio was 0.70 to 1.46. Generic and brand name nevirapine and lamivudine met FDA average bioequivalence criteria. Lack of average bioequivalence for zidovudine was found for C(max) but is not expected to be clinically significant, because the total AUC values were similar between formulations.

The present study compared pharmacokinetic (PK) profile and single-dose tolerability of 2 marketed brands of lamivudine (3TC) 150-mg tablets, Lamivir (Cipla, Mumbai, India) and Epivir (GSK, Basingstoke, UK). The randomized, 2-treatment study was conducted in 24 fasting, healthy, Indian male subjects. Each subject received Epivir and Lamivir formulation separated by 7 days of drug-free washout period. Plasma concentrations of 3TC were used to estimate PK parameters such as maximum observed plasma concentration (Cmax) and area under plasma concentration-time curve (AUCinfinity). Geometric mean ratios (relative to Epivir) and resultant 90% CI of 3TC for Cmax and AUCinfinity were 1.00 (0.89-1.12) and 1.01 (0.94-1.07), respectively. As 90% CIs were entirely within 0.80-1.25 for log-transformed data, the 2 formulations were considered bioequivalent in the extent (AUCinfinity) and rate of absorption (Cmax and time to Cmax [tmax]). The means of primary PK parameters of 3TC, Cmax, and AUCinfinity in Indian subjects were comparable to those previously reported in the literature. Both formulations exhibited similar tolerability under fasting conditions.

We prospectively studied the initial results of 6 months of generic efavirenz-based therapy on the plasma viral load in 40 patients at YRG Centre for AIDS Research and Education, a tertiary HIV referral centre in southern India. The median baseline plasma viral load was 259,000 copies/ml and at 6 months 95% of patients had plasma viral loads less than 400 copies/ml. The data support the use of generic non-nucleoside reverse transcriptase inhibitor-based regimens in resource-limited settings.

Generic fixed-dose combinations of antiretrovirals are frequently prescribed for the treatment of human immunodeficiency virus infection. A randomized, 2-way study was conducted in 24 fasting, healthy, Indian male subjects to assess bioequivalence between a single combination tablet containing lamivudine, stavudine, and nevirapine (treatment A) with respect to separate marketed tablets administered simultaneously (treatment B). Each subject received treatments A and B separated by 19 days of a drug-free washout period. Plasma concentrations of antiretrovirals, determined by a validated liquid chromatography/tandem mass spectrometry assay, were used to assess pharmacokinetic parameters such as maximum observed plasma concentration and area under the plasma concentration curve. Pharmacokinetic parameters were comparable for either treatment. As geometric mean ratios (% treatment A/treatment B) of log-transformed parameters of area under the plasma concentration curve and plasma concentration, as well as their resultant 90% confidence intervals, were within 80% to 125% and 75% to 133%, respectively, 2 treatments were considered bioequivalent in the extent and rate of absorption. Both treatments exhibited similar tolerability under fasting conditions.