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Context: Combating human immunodeficiency virus/acquired immunodeficiency syndrome epidemic has been possible due to advances in prevention strategies and Antiretroviral therapy (ART). Optimal adherence to ART is a major factor in achieving the desired immunological, virological, and patient well‑being outcomes. Several socio‑demographic, patient, treatment, and health‑care system‑related factors influence nonadherent behavior to ART. Aims: This study was planned to assess (1) ART adherence level, (2) factors and reasons associated with nonadherence, and (3) impact of suboptimal adherence on treatment outcomes. Settings and Design: This was a cross‑sectional analytical study of 300 patients in a tertiary care hospital in Puducherry, India. Methods: Random sampling was used to collect data from patient treatment cards and a predesigned structured questionnaire. The pill count method was used to calculate adherence level. Statistical Analysis Used: Nonadherence was chosen as a dependent variable and factors affecting adherence were chosen as independent variables. Test for significance was carried out by Chi‑square test and Fisher’s exact test. Results: Optimal adherence was seen in 68.3%. Factors significantly associated with nonadherence were lower education level, high prior CD4 count, irregular follow‑up, missing doses in the past, and being late for pharmacy pill refills. Adherence was positively associated with mean increase in CD4 count over 6 months. Conclusions: In our study, the adherence rate is suboptimal which can lead to failure of ART. Nonadherence was associated with a decrease in CD4 count overtime. Most of the factors significantly affecting ART adherence were patient behavior related. These factors can be used for target intervention during reinforcement adherence counseling. [ABSTRACT FROM AUTHOR]

Introduction: India has a huge burden of HIV/AIDS infection. Tenofovir-based first-line therapy is the preferred treatment for newly diagnosed cases of HIV infection. Materials and Methods: The present prospective study was done among newly diagnosed cases of HIV infection. The patients were followed up for 6 months from the day of enrollment. Sociodemographic parameters, CD4 counts, and adverse drug reactions (ADRs) were analyzed at baseline and after 6 months. Bivariate and multivariate logistic regression was performed with the occurrence of ADRs as outcome variable. Results: In this study, 67 patients were enrolled with a mean age of 32.75 (±14.39) years. Mean CD4 count at the start of treatment was 241.5/mm3. The mean difference in CD4 count was 383.05/mm3 (standard deviation = 274.9). Dizziness, tingling, numbness of extremities, and muscle cramps were the most common adverse effects. On multivariate logistic regression, the occurrence of ADRs was seen to be significantly higher only in illiterate patients. Conclusion: The present study highlights the importance of long-term follow-up of the patients on antiretroviral therapy. Adequate monitoring of the treatment parameters is of utmost importance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Antiretroviral therapy (ART) is highly toxic, may cause various adverse drug reactions (ADRs). Hence, regular monitoring and reporting of ADRs to ART are essential to ensure the maximum benefit from these medications. The aim/objective of this study is to evaluate the pattern, causality, severity, and preventability of ADRs due to antiretroviral drugs. Materials and Methods: A descriptive observational study was carried out on people living with human immunodeficiency virus (HIV), at ART center of SMS Medical College and attached group of hospitals, Jaipur, after due approval from the Institutional Ethics Committee. ADRs due to various ART regimens were studied over a period of 12 months. Clinical information of ADRs and other relevant details was collected on predesigned pro forma and causality, severity, and preventability of reported ADRs were duly assessed. Results: Five hundred and twenty-four HIV patients taking ART presented with a total of 996 ADRs. Maximum ADRs were implicated by tenofovir + lamivudine + efavirenz and were related to the central nervous system (35.3%) and gastrointestinal system (19.6%). Other ART caused ADRs of anemia, rashes, renal impairment, hepatobiliary impairment, and rare ADR of Steven-Johnson Syndrome (S-J Syndrome) and gynecomastia. Among encountered ADRs, 73.8% were preventable, whereas 26.2% were not preventable. Causality assessment was found to be possible, probable, and certain in 72.7%, 24.9%, and 2.4% of ADRs, respectively. Conclusion: ART is associated with a broad range of ADRs, ranging from mild to life-threatening adverse reactions. The activities of pharmacovigilance, ADR monitoring, and reporting are mandatory to improve the drug safety. The following core competencies are addressed in this article: Medical knowledge, Patient care, Practice-based learning and improvement, and Systems-based practice. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is highly prevalent in HIV-exposed perinatally uninfected infants (HEUs) increasing the risk of morbidity and mortality throughout the life course. We set out to compare the effect of postnatal exposure to maternal antiretroviral therapy (mART) in breastmilk versus infant Nevirapine prophylaxis (iNVP) on somatic growth of HEUs in the randomized PROMISE trial. Methods and findings: We randomized 2431 mothers with HIV and their 2444 HEUs from six African countries and India 6–14 days after delivery to mART or iNVP for prevention of breastmilk HIV transmission. The mART regimen contained tenofovir/emtricitabine (99%) plus lopinavir/ritonavir. Infant growth parameters were compared at postnatal week 10, 26, 74 and 104 using World Health Organization (WHO) z-scores for length-for-age (LAZ), weight-for-age (WAZ), and head circumference-for-age (HCAZ). Week 26 LAZ was the primary endpoint measure. Student T-tests compared mean LAZ, WAZ, and HCAZ; estimated mean and 95% confidence interval (CI) are presented. Maternal and infant baseline characteristics were comparable between study arms. The estimated median breastfeeding duration was 70 weeks. After a mean follow-up of 88 weeks, mean LAZ and WAZ were below the WHO reference population mean at all timepoints, whereas mean HCAZ was not. The mART and iNVP arms did not differ for the primary outcome measure of LAZ at week 26 (p-value = 0.39; estimated mean difference (95%CI) of -0.05 (-0.18, 0.07)) or any of the other secondary growth outcome measures or timepoints (all p-values≥0.16). Secondary analyses of the primary outcome measure adjusting for week 0 LAZ and other covariates did not change these results (all p-values≥0.09). However, infants assigned to mART were more likely to have stunting compared to iNVP infants at week 26 (odds ratio (95% CI): 1.28 (1.05, 1.57)). Conclusions: In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head circumference with no clinically relevant differences between the groups. Despite breastfeeding into the second year of life, length and weight were below reference population means at all ages in both arms. Further investment is needed to optimize postnatal growth of infants born to women with HIV. Clinical trial registration: ClinicalTrials.gov number NCT01061151. [ABSTRACT FROM AUTHOR]

HIV‐infected patients have a higher risk of developing cutaneous reactions to drugs than the general population. Severe cutaneous adverse reactions (SCARs) are not uncommon in patients taking antiretroviral therapy (HAART]. To evaluate HLA class I and II allele frequencies in HIV patients on HAART who develop SCARs due to nevirapine (NVP] or efavirenz (EFZ] containing regime and compare this genotype composition with HAART tolerant patients and healthy organ donors. A case‐control study for 4 years was conducted with four subsets of patients hailing from north‐east India:Cohort 1‐ HIV seropositive patients who developed SCARs due to EFZ (n = 8];Cohort 2 ‐ HIV seropositive patients who developed SCARs due to NVP (n = 15]; Cohort 3 ‐HIV seropositive NVP/EFZ‐tolerant patients (n = 18]; Cohort 4 ‐ Healthy HIV seronegative organ donors (n = 169].Cohort 3 & 4 acted as control‐group. These patients were genotyped for the HLA‐A, HLA‐B, HLA‐C, HLA‐DRB1, HLA‐DQB1, and HLA‐DPB1 by a sequence‐based HLA typing method. HLA‐DRB1*03:01 allele revealed a significant association with EFZ regimen‐induced SCARs in 62.5% patients compared with only 5.56% observed in HAART‐tolerant patients and 4.14% in healthy organ. HLA‐B*3505was found to be significantly associated with NVP induced SCARs. We found significant novel association of HLA‐DRB1*03:01 with EFZ induced SCARs in North‐East Indian HIV patients. Thus, HLA‐DRB*03:01 may be useful as a genetic marker to avoid EFZ induced serious cutaneous rashes. The molecular HLA characterization of these alleles may provide a novel insight into the immunological basis of the antiretroviral drug reactions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population., Objective: This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens., Methods: A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks., Results: At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected., Conclusion: Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abstract: Introduction: Dolutegravir (DTG)‐based antiretroviral therapy (ART) is recommended for first‐line HIV treatment in the US and Europe. Efavirenz (EFV)‐based regimens remain the standard of care (SOC) in India. We examined the clinical and economic impact of DTG‐based first‐line ART in the setting of India's recent guidelines change to treating all patients with HIV infection regardless of CD4 count. Methods: We used a microsimulation of HIV disease, the Cost‐Effectiveness of Preventing AIDS Complications (CEPAC)‐International model, to project outcomes in ART‐naive patients under two strategies: (1) SOC: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC); and (2) DTG: DTG + TDF/3TC. Regimen‐specific inputs, including virologic suppression at 48 weeks (SOC: 82% vs. DTG: 90%) and annual costs ($98 vs. $102), were informed by clinical trial data and other sources and varied widely in sensitivity analysis. We compared incremental cost‐effectiveness ratios (ICERs), measured in $/year of life saved (YLS), to India's per capita gross domestic product ($1600 in 2015). We compared the budget impact and HIV transmission effects of the two strategies for the estimated 444,000 and 916,000 patients likely to initiate ART in India over the next 2 and 5 years. Results: Compared to SOC, DTG improved 5‐year survival from 76.7% to 83.0%, increased life expectancy from 22.0 to 24.8 years (14.0 to 15.5 years, discounted), averted 13,000 transmitted HIV infections over 5 years, increased discounted lifetime care costs from $3040 to $3240, and resulted in a lifetime ICER of $130/YLS, less than 10% of India's per capita GDP in 2015. DTG maintained an ICER below 50% of India's per capita GDP as long as the annual three‐drug regimen cost was ≤$180/year. Over a 2‐ or 5‐year horizon, total undiscounted outlays for HIV‐related care were virtually the same for both strategies. Conclusions: A generic DTG‐based regimen is likely to be cost‐effective and should be recommended for initial therapy of HIV infection in India. [ABSTRACT FROM AUTHOR]

Background: According to World Health Organization (WHO) guidelines, which have also been adopted by the National AIDS Control Organization (NACO), India, Efavirenz-based Anti-Retroviral Therapy (ART) is better in Human-Immunodeficiency-Virus (HIV)-infected patients who are also being treated with Rifampicin-based Anti-Tuberculous Therapy (ATT). However, Efavirenz is much more expensive. We hypothesize that Nevirapine is a cheaper alternative that possesses equal efficacy as Efavirenz in HIV-Tuberculosis (TB) co-infected patients.Methods: A parallel open-label randomized clinical trial was conducted at All India Institute of Medical Sciences (AIIMS), New Delhi and National AIDS Research Institute (NARI), Pune. Those who were ART-naïve and co-infected with TB were randomized to receive either Nevirapine (Group 1)- or Efavirenz (Group 2)-based ART along with Rifampicin-based ATT. ATT was begun first in ART-naïve patients according to the NACO guidelines, with a median of 27 days between ATT and ART in both groups. The primary endpoint was a composite unfavourable outcome (death and/or ART failure) at 96 weeks, and the secondary outcome was successful TB treatment at 48 weeks.Results: A total of 284 patients (mean age 36.7 ± 8.1 years) were randomized in a 1:1 ratio to receive either Nevirapine (n = 144)- or Efavirenz (n = 140)-based ART after a median ATT-ART gap of 27 days. The median CD4 count was 105 cells/μl, with a median viral load of 820,200 copies/μl and no significant difference between the groups. Composite unfavourable outcomes were reported in 49 patients in the Nevirapine group and 51 patients in the Efavirenz group (35.3% vs. 36.9%; hazard ratio, 0.95, 95% confidence interval (CI), 0.63,1.43, adjusted). There was no difference in successful TB treatment outcome between the groups (71.5% vs. 65.6%, 95% CI -3.8,17.9, adjusted). The results were similar, showing no difference between the groups in the two centres of the study after adjusting for disease stage.Conclusions: Composite unfavourable outcome in HIV-TB co-infected patients who were ART-naïve showed no statistically significant difference in the Nevirapine or Efavirenz groups.. Therefore, Nevirapine-based ART is a reasonable alternative to Efavirenz in resource-limited settings. However, multi-centric studies with larger sample sizes are required to confirm these findings.Trial Registration: NCT01805258 (Retrospectively registered on March 6, 2013) Date of registration: March 2013. [ABSTRACT FROM AUTHOR]

The article discusses a retrospective observational study that compares the efficacy and safety of two different antiretroviral regimens in tertiary care hospital, including stavudine lamivudine nevirapine (SLN) ) and stavudine lamivudine efavirenz (SLE). It states that combined retroviral therapy has reduced morbidity and mortality in human immunodeficiency virus (HIV) patients. The study concludes that the treatment increased the CD4 count as well as Hemoglobin percent and weight.

BACKGROUND: Greatest challenges for clinician is to recognize risk factors for clinically significant drug interactions (CSDIs). There is a lack of awareness about CSDIs among healthcare professionals in India. OBJECTIVE: To recognize all possible risk factors for drug-drug interactions (DDIs) and to identify clinically significant drug interactions (CSDIs), the prevalence, pattern of occurrence of DDIs in People Living with HIV (PLW-HIV) receiving highly active antiretroviral therapy (HAART) and concomitant medications. METHODS: A retrospective medical record review was carried out by clinical pharmacist with ethics committee approval. Case files of HIV patients receiving HAART with concomitant medications were analyzed for CSDIs using University of Liverpool drug interaction database and CSDIs were classified based on red flag indication (RFI) or contraindicated drugdrug interaction (XDDIs) and orange flag indication (OFI) or DDIs that needs close monitoring. Patients with DDIs (cases) and patients without DDIs (controls) were compared with Chi-square tests. P value <0.05 was considered as statistically significant. RESULTS: A total of 240 HIV patients' cases were screened. Out of which 267 DDIs were reported in 107 patients. Prevalence of DDIs was higher in male 71 (66.4%) compared to female 36 (33.6%). On zero-inflated poisson regression analysis, factors of polypharmacy, opportunistic infections, comorbid condition like Ischemic heart disease, respiratory tract infections, and psychiatric disorder were found to be predictors of high risk factors for DDIs toHAART. Fourteen XDDIs with RFI and two hundred fifty three DDIs with OFI were reported. XDDIs were atazanavir with fluconazole 4 (28.6%), ritonavir with fluconazole 4 (28.6%), nevirapine with rifampicin 2 (14.4%), ritonavir with quetiapine, atazanavir with pantoprazole. Pharmacokinetic DDIs were highest 238 (89.1%). Sixteen DDIs were reported in a single patient. The majority 97 (90.6%) patients had developed ≤5 DDIs, 8 (7.5%) developed six to eleven DDIs. The highest DDIs were reported with efavirenz 49 (18.4%) and zidovudine 44 (16.5%) based HAART regimen. CONCLUSION: In India, with the increasing access to HAART usage, Clinician must focus to pay attention to recognize possible risk factors for CSDIs associated with HAART regimen and strictly to avoid "Red Flag Indication combinations" while prescribing so as to prevent CSDIs. [ABSTRACT FROM AUTHOR]

The article offers information on the adverse effects of antiretroviral therapy in a tertiary care hospital in India. Ninety patients who were undergoing antiretroviral therapy were evaluated prospectively over a period of six months and were examined for adverse effects. Most of the adverse effects were observed in females.

Background: In 2010, WHO expanded previously-recommended indications for anti-retroviral treatment to include all HIVinfected TB patients irrespective of CD4 count. India, however, still limits ART to those TB patients with CD4 counts <350/ mm3 or with extrapulmonary TB manifestations. We sought to evaluate the additional number of patients that would be initiated on ART if India adopted the current 2010 WHO ART guidelines for HIV-infected TB patients. Methods: We evaluated all TB patients recorded in treatment registers of the Revised National TB Control Programme in June 2010 in the high-HIV prevalence state of Karnataka, and cross-matched HIV-infected TB patients with ART programme records. Results: Of 6182 TB patients registered, HIV status was ascertained for 5761(93%) and 710(12%) were HIV-infected. 146(21%) HIV-infected TB patients were on ART prior to TB diagnosis. Of the remaining 564, 497(88%) were assessed for ART eligibility; of these, 436(88%) were eligible for ART according to 2006 WHO ART guidelines. Altogether, 487(69%) HIV-infected TB patients received ART during TB treatment. About 80% started ART within 8 weeks of TB treatment and 95% received an efavirenz based regimen. Conclusion: In Karnataka, India, about nine out of ten HIV-infected TB patients were eligible for ART according to 2006 WHO ART guidelines. The efficiency of HIV case finding, ART evaluation, and ART initiation was relatively high, with 78% of eligible HIV-infected patients actually initiated on ART, and 80% within 8 weeks of diagnosis. ART could be extended to all HIVinfected TB patients irrespective of CD4 count with relatively little additional burden on the national ART programme. [ABSTRACT FROM AUTHOR]