Effectiveness, Weight Changes, and Metabolic Outcomes on Switch to Generic Dolutegravir/Lamivudine Among People with HIV in Western India: An Observational Study.

We assessed the effectiveness and safety of switching to generic dolutegravir/lamivudine (DTG/3TC) among People living with Human Immunodeficiency Virus (PWH) in Western India. In this single-center, retrospective observational study, PWH, who switched to DTG/3TC, were followed for virologic, immunologic, and clinical effectiveness, and safety, including weight changes, hyperglycemia, and dyslipidemia. Multivariate linear mixed-effects models were used to predict average change in weight adjusted for age, sex, duration of previous antiretroviral (ARV) regimens, and baseline weight. From May 2017 to July 2022, out of 434 PWH switched to DTG/3TC, 304 with at least 1 follow-up visit were included. Median [interquartile range (IQR)] age was 54 (IQR 49-61) years and 70.1% were male. Prevalence of baseline comorbidities was 57.9% (hypertension-41.5%, chronic kidney disease-40.9%, and diabetes mellitus-18.8%). Reasons for switch were affordability (47.4%), desire for simplification (41.8%), ARV toxicities (19.1%), and concern about potential toxicities (10.2%). Median (IQR) duration of follow-up on DTG/3TC was 40 (IQR 31-49) weeks. No virologic failure was observed. Rates of virologic suppression [viral load (VL) ≤20 copies/mL or target not detected (TND)] at 12, 24, 48, 72, 96 and 120 weeks were 95.2%, 95.9%, 90%, 100%, 81.3%, and 88.4%, respectively. Only 9 (3%) PWH permanently discontinued DTG/3TC. Predicted adjusted mean weight gain of +3.3 kg was observed at 96 weeks. Switching from tenofovir disoproxil fumarate (TDF)/emtricitabine or lamivudine (XTC)/non-nucleoside reverse transcriptase inhibitor (NNRTI) and duration on DTG/3TC were significantly associated with weight gain. Apart from trend in worsening hyperglycemia (nine PWH with new onset diabetes), no clinically significant change in lipids and estimated glomerular filtration rate (eGFR) was documented. Switching to DTG/3TC is an effective and safe option among virologically suppressed PWH with high comorbidity burden in India. In view of the several advantages of DTG/3TC, it may be considered for potential scale-up in the right population, both in private and public health care settings in India.

An expanded description of Cnemaspis gracilis (Beddome 1870) (Squamata: Gekkonidae) based on recent material.

Cnemaspis gracilis is a poorly known species that has been reported from across southern India, with 11 named species within the clade. The species is known only from the type series, as many other records from areas outside the type locality have turned out to represent distinct species. We provide an expanded morphological description of the species based on topotypic material and other samples that were assigned using genetic data. Cnemaspis gracilis is now known with certainty from three localities in the vicinity of Palakkad, Palakkad District, Kerala, and Valparai town, Coimbatore district, Tamil Nadu, besides from an introduced population in the Timber Market, Kolhapur city, Kolhapur district, Maharashtra, India. The species is 7.6-15.8 % divergent on the ND2 gene from described members of the gracilis clade and can be diagnosed by a combination of morphological characters including body size, number of paravertebral tubercles between limb insertions, number of dorsal tubercle rows, number of ventral scale rows across the belly, number of femoral and precloacal pores and poreless scales separating these series in males, and the presence of a single central black ocellus on the neck and a smaller one on the occiput. The assignment of extant populations to the species, a detailed morphological description and genetic data will allow the description of many more species from within this diverse clade of diurnal geckos.

Molecular docking and optical sensor studies based on 2,4-diamino pyrimidine-5-carbonitriles for detection of Hg2.

An organic chemical sensor based on pyrimidine was successfully produced through the green reaction between aromatic aldehyde, malononitrile, and guanidine carbonate using SBA-Pr-SO3H. This fluorescence intensity of chemosensor (2,4-diamino-6-(phenyl)pyrimidine-5-carbonitrile) decreases by the addition of Hg2+ and its detection limit is about 14.89 × 10-5 M, in fact, through the green synthesis, the ligand was yielded to detect Hg2+ and the importance of ligand was considered in docking studies. The molecular docking of 2,4-diamino-6-(phenyl)pyrimidine-5-carbonitrile compound has been done with the protein selective estrogen receptor 5ACC complexed with (Azd9496), Human Anaplastic Lymphoma Kinase Pdb; 2xp2 complex with crizotinib (PF-02341066) and human wee1 kinase Pdb; 5vc3 complexed with bosutinib. The ligands 2,4-diamino-6-(phenyl)pyrimidine-5-carbonitrile generate very good docking results with the protein Pdb; 2xp2, which is responsible for effective tumor growth inhibition.

Design, synthesis and evaluation of side-chain hydroxylated derivatives of lithocholic acid as potent agonists of the vitamin D receptor (VDR).

A high number of biologically active and low-calcemic secosteroidal ligands of the vitamin D receptor (VDR) have been developed, some of which are already used clinically although with limited success in the treatment of hyperproliferative diseases because the required pharmaceutical dosages induce toxicity. We describe here the in silico design, synthesis, structural analysis and biological evaluation of two novel active lithocholic acid derivatives hydroxylated at the side chain as highly potent inhibitors of atopic dermatitis-relevant keratinocyte inflammation of potential therapeutic interest.

Long-coronavirus disease among people living with HIV in western India: An observational study.

BACKGROUND: Long-COVID is emerging as a significant problem among individuals who recovered from COVID-19. Scant information is available on the prevalence, characteristics, and risk factors for long-COVID among people living with HIV (PLHIV). SETTING: A tertiary level, private, HIV clinic in western India. METHODS: A prospective, observational study was conducted to assess the prevalence of long-COVID among PLHIV. Long-COVID was defined as the presence of at least one symptom after 30 days of illness onset. A questionnaire for assessing general, cardiorespiratory, neuro-psychiatric, and gastro-intestinal symptoms was used to screen individuals with history of confirmed COVID-19. Data on demographics, HIV-related variables, comorbidities, and severity of COVID-19 were abstracted from electronic medical records. Univariate and multivariate logistic regression were used to identify risk factors for long-COVID. RESULTS: Ninety-four PLHIV were screened for long-COVID. Median (interquartile range [IQR]) age was 51 (47-56) years and 73.4% were males. The majority (76.6%) had a history of asymptomatic-mild COVID-19 illness. The prevalence of long-COVID was 43.6% (95% confidence interval [CI], 33.4-54.2). Moderate-severe COVID-19 illness was significantly associated with long-COVID (adjusted odds ratio, 4.7; 95% CI, 1.4-17.9; p = .016). Among individuals with long-COVID, cough (22.3%) and fatigue (19.1%) were the commonest symptoms. The median (IQR) duration for resolution of symptoms was 15 (7-30) days. Ten individuals (10.6%) had persistent symptoms at a median of 109 days since the onset of COVID-19. CONCLUSION: Long-COVID is common among PLHIV with moderate-severe acute COVID-19 illness. There is a need for integration of long-COVID diagnosis and care services within antiretroviral therapy clinics for PLHIV with COVID-19.

Short Communication: Coronavirus Disease 19 Among People Living with HIV in Western India: An Observational Cohort Study.

A retrospective cohort study was conducted to assess clinical characteristics and outcomes of coronavirus disease-19 (COVID-19) among people living with HIV (PLHIV) in western India. Out of 86 PLHIV with COVID-19 illness, 19.7% had severe/critical illness and 6 (6.9%) individuals died. Median (interquartile range) age was 51 (47-56) years and 77.6% were male. Eighty-five PLHIV were on antiretroviral treatment with 98% having a viral load <200 copies/mL. Hypertension (HTN) (38.3%) and diabetes mellitus (17.4%) were commonest comorbidities. Fifty-eight percent PLHIV were hospitalized while 6.9% individuals needed intensive care. Presence of medical comorbidity was significantly associated with severe/critical COVID-19, whereas HTN was significantly associated with mortality. Recovery from COVID-19 was documented in 93% PLHIV. In conclusion, PLHIV in western India have similar COVID-19 clinical outcomes as compared with those reported historically among general population. Presence of medical comorbidities rather than HIV-related disease characteristics is associated with severe COVID-19 illness.

Lithocholic acid-based design of noncalcemic vitamin D receptor agonists.

The hypercalcemic effects of the hormone 1α,25-dihydroxyvitamin D3 (calcitriol) and most of known vitamin D metabolites and analogs call for the development of non secosteroidal vitamin D receptor (VDR) ligands as new selective and noncalcemic agonists for treatment of hyperproliferative diseases. We report on the in silico design and stereoselective synthesis of six lithocholic acid derivatives as well as on the calcemic activity of a potent LCA derivative and its crystallographic structure in complex with zVDR LBD. The low calcemic activity of this compound in comparison with the native hormone makes it of potential therapeutic value. Structure-function relationships provide the basis for the development of even more potent and selective lithocholic acid-based VDR ligands.

Effectiveness of dolutegravir-based antiretroviral treatment for HIV-2 infection: retrospective observational study from Western India.

BACKGROUND: Data on the use of dolutegravir for treatment of HIV-2 infection are limited. OBJECTIVES: To assess the effectiveness of dolutegravir in people living with HIV-2 (PLHIV-2). METHODS: A retrospective chart review was performed in two clinics in Western India. PLHIV-2 initiated on dolutegravir-based regimens were included. Response to treatment in both treatment-naive (TN) and treatment-experienced (TE; substitution and not in the context of failure) was assessed by CD4 counts and HIV-2 viral load (VL) in a proportion of individuals. The primary objective was to assess immunological effectiveness (absence of a drop in absolute CD4 counts by more than 30% of baseline). Change in absolute CD4 counts was assessed by fitting a mixed-effects model. RESULTS: Sixty-two PLHIV-2 treated with dolutegravir were included. The immunological effectiveness rates (95% CI) were 91.9% (82.4%-96.5%), 92% (81.1%-96.8%) and 91.6% (64.6%-98.5%) amongst all, TE and TN individuals, respectively. Median change in absolute CD4 counts at 6, 12 and 18 months were +29 cells/mm3, +101 cells/mm3 and +72 cells/mm3, respectively. The virological effectiveness rates (HIV-2 VL <100 copies/mL) (95% CI) for all, TE and TN individuals were 88.8% (74.6%-95%), 89.6% (73.6%-96.4%) and 85.7% (48.6%-97.4%), respectively. Three clinical events were documented: spinal tuberculosis, relapsed non-Hodgkin's lymphoma and herpes simplex virus retinitis. One individual reported self-limiting somnolence. CONCLUSIONS: Dolutegravir was well tolerated and associated with immunological, virological and clinical effectiveness in both TN and TE PLHIV-2 in a large cohort from Western India. Dolutegravir-based ART is an excellent option for treatment of individuals with HIV-2 infection.

High prevalence of multi drug resistant tuberculosis in people living with HIV in Western India.

BACKGROUND: Most studies assessing drug resistant tuberculosis (DRTB) in human immunodeficiency virus (HIV) co-infected patients in India have used conventional culture- based systems to diagnose DRTB that have a longer turnaround time leading to risk of amplification of resistance to an empirical regimen. We determined the prevalence of DRTB amongst people living with HIV (PLHIV) using the line probe assay and determined risk factors associated with the presence of multi drug resistant tuberculosis (MDRTB). METHODS: A Cross-sectional study was undertaken at Poona Hospital and Research Center (PHRC) and the Institute of Infectious Diseases, two tertiary level private care centers in Pune, India. Consenting PLHIV with confirmed Pulmonary TB (PTB) and/or extra-pulmonary TB (EPTB) diagnosed based on detection of Mycobacterium TB by line probe assay (Geno Type MTBDRplus version 2) on clinical specimens were included. Those with documented past history of DRTB were excluded. Resistance against anti-TB drugs was determined by the same assay. The prevalence of any form of drug resistant TB (DRTB), MDRTB, Rifampicin resistant TB (RRTB) and Isoniazid (INH) mono-resistant TB were determined as the proportion of these amongst all included PLHIV-TB. A multivariate analysis was conducted to determine risk factors that were statistically associated with MDRTB, DRTB, RRTB and INH mono-resistant TB. RESULTS: Two hundred PLHIV were recruited. The prevalence (95% CI) of MDRTB, INH mono- resistance and RR resistance was 12.5% (7.9-17.1%), 9% (6.9-11.2%) and 2.5% (1.4-3.6%), respectively. The prevalence (95% CI) of MDRTB among new and relapsed patients was 8.8% (6.5-11.1%) and 23.1% (17.2-28.9%), respectively. Tuberculosis relapse was the only factor significantly associated with MDRTB, DRTB and INH mono-resistant TB. CONCLUSION: We document a high prevalence of drug resistance to anti-TB drugs including MDRTB among PLHIV in our setting using Geno Type MTBDRplus directly on clinical specimens. This validates the WHO recommendation of performing routine rapid molecular resistance testing prior to initiating anti-TB treatment among all PLHIV with presumptive TB. Using rapid molecular testing especially Geno Type MTBDRplus (that detects resistance to INH and Rifampicin simultaneously) reduces the turn-around time helping in optimizing treatment.

AIDS Cholangiopathy Secondary to Cytomegalovirus as Possible Unmasking Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Individual: Case Report and Review of the Literature.

We present the first case report of cytomegalovirus (CMV) cholangiopathy as possible immune reconstitution inflammatory syndrome (IRIS) in a human immunodeficiency virus (HIV)-infected individual, within two months of starting effective HAART. The patient presented with abdominal pain, nausea, vomiting, decreased appetite, and jaundice. The patient was diagnosed on ERCP as AIDS cholangiopathy, and biopsy of the ampulla showed acute inflammation with CMV inclusion bodies. The patient underwent sphincterotomy with CBD stenting and HAART continued without use of ganciclovir or valganciclovir. On follow-up, the patient achieved clinical and histopathological cure, which was demonstrated on repeat ampullary biopsy.

High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.

BACKGROUND: There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. METHODS: We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history). Plasma viral loads (PVL) are performed 6 months post-initiation and annually thereafter. Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9 years) while median duration of ART prior to switching to MVC was 13 years. Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1 Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and sustained it for 2.3 years. Median CD4 count change from baseline was +117 (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months respectively. Repeat tropism among patients with virologic failure demonstrated R5 virus. CONCLUSIONS: High rates of virologic failure was seen when MVC was used amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow up visit. RESULTS: Data on 13 PLHIV were analyze.

Clinical profile of HIV infected patients attending a HIV referral clinic in Pune, India.

BACKGROUND & OBJECTIVES: Human immunodeficiency virus (HIV) has infected several million individuals in India. Various interventions have been implemented for early detection and prevention of transmission of HIV infection. This has progressively changed the clinical profile of HIV infected individuals and this study documents the clinical presentation of individuals positive for HIV in 2010, in Pune, Maharashtra, India. METHODS: This cross-sectional study included subjects who had come to the HIV referral clinic for HIV testing from January to December 2010. Children as well as individuals with indeterminate HIV result were excluded from the study, and data for 1546 subjects were finally analysed. RESULTS: The HIV positivity rate among all referred cases for the year 2010 was 35 per cent (male 55% and females 45%). The median age (Q1, Q3) was 31 (25.75, 39) yr. The median CD4 cell count for all HIV infected individuals (whose CD4 count was available n=345) was 241 cells/µl and for asymptomatic HIV infected individuals was 319 cells/µl. There were 673 (43.5%) symptomatic and 873 (56.5%) asymptomatic participants. Fever, breathlessness, cough with expectoration, weight loss, loss of appetite, generalized weakness, pallor and lymphadenopathy (axillary and cervical) were found to be associated (P<0.001) with HIV positivity. On multivariate analysis, history of Herpes zoster [AOR 11.314 (6.111-20.949)] and TB [AOR 11.214 (6.111-20.949)] was associated with HIV positivity. INTERPRETATION & CONCLUSIONS: Signs and symptoms associated with HIV positivity observed in this study can be used by health care providers to detect HIV infection early. Moreover, similar to HIV testing in patients with tuberculosis, strategies can be developed for considering Herpes zoster as a predictor of HIV infection.