Background: The study analyses several first line and second line drugs, CD4 counts and viral load in patients experiencing treatment failure over a period of 1 to 6 years of first line ...Antiretroviral Therapy (ART). The study emphasizes the implementation of tailor-made regimen and the drug resistance testing in the national programme in India. Aim and Objectives: A study on the efficacy of the first line individualized regimen of HIV-1 subtype C infected North Indian population and recommendation of first line tailor made regimen after detection of Drug Resistance Mutations (DRM) associated with first line drugs. Material and Methods: The study of HIV-1 patients taking first line ART (period 2009-2016) was conducted at ART centre, S.N Medical College, Agra, India. The follow-up of fiftyseven patients were conducted after a confirmation of genotyping test. The primary data analysis was done on the data availability based on inclusion criteria to observe the correlation between the CD4 counts and viral loads (markers of the clinical outcome) of the individual North Indian patients infected with HIV-1 Subtype C. The DRM in individual patients were analysed through the drug resistance database, Stanford University, United States of America. The study design was based on the primary data analysis of the 57 patients' drug profiles which were associated with DRM during the first line ART. The data of the resistance associated drugs, CD4 counts, viral loads of the individual patient were compiled and the patterns of drug resistance profiles were statistically analysed using Microsoft Excel 2016 and SPSS Version 22. The normality of the data was checked by Shapiro-Wilk test (p<0.05). Results: Fifty-one patients were detected with DRM. Out of 57 first line ART failure patients, 45 patients were continuing with first line and second line ART in alive condition. Twelve patients died during the treatment of first line and second line ART. Twenty four patients whose complete data of CD4 counts and viral load were available, did not show difference in drug adherence. Despite being resistant to most of the first line drugs, CD4 count increased and viral load decreased in 12 patients. Both CD4 count and viral load increased in 3 patients. Both markers declined in 2 patients while 7 of them with decrease in CD4 counts showed increase in viral loads. Median duration of treatment was 41.84 months while median treatment adherence was 98.25%. Among the 24 patients, 16 patients were shifted on second line regimen. Conclusion: The study suggests the provision of a tailor-made first line and second line individualized regimen to each patient under a policy program of National AIDS Control Organization (NACO), Govt. of India. The implementation of drug resistance testing of first- and second-line therapy is very essential for changing the suitable regimen to increase CD4 counts and decrease viral load of individual patients.
Documenting behavior change through ongoing counseling is critical when HIV counseling strategies are being formulated. This study aims to demonstrate risk reduction behavior in a year in the context ...of HIV related problems in men and women attending ongoing counseling at a Voluntary Counseling and Testing Centre during their regular follow-ups. This is a descriptive study based on one year observation of 253 HIV infected men (112) and women (141) attending a Voluntary Counseling and Testing Centre for ongoing counseling of a research institute in Pune during six-monthly follow-up visits. A face to face interview using a 22 item semi-structured questionnaire administered after an informed consent to collect data on sexual history since last visit, condom use, HIV related problems etc. SPSS and Pearson's chi-square test Association was used. The HIV infected ever married men (91%) and women (98% married including widows) have significant differences with respect to age, marital status, occupation (p < 0.01), and similarity in education. There is an increase in condom usage with spouse with advancing follow-up i.e. increasing dose effect through ongoing counseling is observed, it being statistically significant for men (P value < 0.004). Consistent condom use with other partners is reported by men and widows. The participants reported problems ranging from health, economic, social, support issues like stigma and concerns of future. Economic problems are reported in those having frequent follow-ups, being more in men than women (34%, 29% resp.).An ongoing counseling of follow-up participants is a useful opportunity to reinforce behavior change, demonstrated by safer behaviors, especially reduction in partners, consistent condom use with spouse and other partners. The problems faced by HIV infected require support of Non- governmental organizations to address their problems like alternative source of incomes, health care, children's education, and women's right to property etc. Networking of Non- governmental organizations for support, capacity strengthening including gender sensitivity should go hand in hand with ongoing counseling to bring sustained behavior change when other interventions are planned for HIV infected persons. PUBLICATION ABSTRACT
The CYP2R1 gene express the enzyme 25-hydroxylase, involved in the synthesis of major circulating vitamin D metabolite 25-hydroxyvitaminD 25(OH)D. CYP2R1 gene variants have been reported to be ...associated with altered 25(OH)D level and associated with the development of active disease including tuberculosis (TB). The aim of the present study was to understand the association of rs10741657 (G/A) and rs2060793(A/G) CYP2R1 gene polymorphisms with tuberculosis susceptibility/protection in 104 Healthy controls (HCs) and 105 pulmonary tuberculosis (PTB) patients and to understand the influence of gene variants on 25(OH)D levels in South Indian population. Genotyping was performed by polymerase chain reaction trailed by restriction fragment length polymorphism (PCR-RFLP) method. Plasma samples were used for 25(OH)D level estimation by ELISA method. In rs10741657, under a dominant model (GG vs AG + AA), “AG” and “AA” genotypes as well as in rs2060793 under an overdominant model (GA vs GG + AA), “GA” genotype were significantly associated with protection to pulmonary tuberculosis. Based on sex, rs10741657 “AG” was significantly associated with protection and “GG” was significantly associated with susceptibility to TB in males. A sufficient vitamin D level was found with rs10741657 “AA” and “AG” genotypes and “GG” genotype associated with 81.8% of vitamin D deficiency in PTB individuals. In conclusion, rs10741657 “AG” and “AA” genotypes were associated with higher 25(OH)D levels and protection to TB. The lower 25(OH)D levels associated with rs10741657 “GG” genotype individuals may be recommended for higher vitamin D supplementation for better outcome from the disease. Further studies with large sample size are needed to confirm this study finding.
Vitamin D deficiency is often associated with tuberculosis susceptibility. Variants of vitamin D binding protein gene are reported to be associated with blood circulating concentration of 25(OH)D ...levels. The aim of the present study was to understand the association of rs7041 (G/T) and rs4588 (C/A) polymorphisms with tuberculosis susceptibility/protection in 125 Healthy controls (HCs) and 125 pulmonary tuberculosis (PTB) patients and to understand whether the gene variants have any influence on 25(OH)D levels in South Indian population. The genotyping for both the polymorphisms were done by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) method. 25(OH)D levels were estimated by ELISA method. The results revealed that under codominant model, rs4588 ‘CA' genotype significantly associated with TB susceptibility OR: 1.47 (0.85–2.55); p = 0.049 and associated with 47.4% 25(OH)D deficiency in PTB patients. Whereas, under recessive model (‘AA' vs ‘CC' + ‘CA') rs4588 ‘AA' genotype significantly associated with TB protection OR: 0.14 (0.02–1.29); p = 0.042. Whereas in rs7041 polymorphism, under overdominant model (‘TG' vs ‘GG+’TT'), no association was found. Increased 25(OH)D levels were found with rs7041 “GG”, and rs4588 “CC” genotype in HCs and PTB patients. Haplotypes ‘TA' and ‘TC' associated with susceptibility to TB in males compared with females ‘TA' - OR: 4.18 (1.84–9.49); ‘TC' - OR: 3.63 (1.34–9.84). The results suggest that the heterozygous genotype rs4588 “CA” significantly associated with susceptibility while rs4588 “AA” genotype significantly associated with TB protection. Gene variants with 25(OH)D deficiency revealed no significant association due to limited sample size. However, in rs7041 “TG” and rs4588 “CA” genotype was associated with 61.1% and 47.4% 25(OH)D deficiency (OR > 2.0) in PTB patients. Future studies with larger sample size are needed to confirm this study finding.
Tuberculosis is a major communicable disease, which has existed in the world for over two millennia. It affects people from all countries, more in some and less in others. The Asian countries have ...over 60% of the global TB burden. Specific treatment for tuberculosis was available only after the 1943 discovery of streptomycin. Many other anti-tuberculosis drugs have since been discovered and their efficacies established through controlled clinical trials. Table 1 presents a list of commonly used anti-tuberculosis drugs that are in use currently. Concerted efforts by researchers spread over the globe have provided us the scientific basis of treatment and management of TB patients through carefully conducted, controlled clinical trials in patients in different countries and settings. The World Health Organization was closely associated with most of those trials and has played a key role in the formulation of national tuberculosis programs in most countries adopting a uniform DOTS (Directly Observed Therapy, Short Course) strategy, which now forms the basis of TB control programs in 184 countries in the world (World Health Organization, 2007a). In the early introduction of chemotherapy, the incidence and prevalence of TB was high in many Asian countries. Mortality was high, diagnosis was delayed, and patients presented with advanced disease including some with acute fulminant tuberculosis, which often ended in death. Today, diagnosis is early, incidence and prevalence of tuberculosis have declined, most patients have access to drugs and are successfully treated, mortality has considerably reduced and very few patients present with acute fulminant TB. Currently available regimens under DOTS strategy include highly potent drugs of streptomycin (S), isoniazid (H), rifampicin (R), ethambutol (E), and pyrazinamide (Z), which form the sheet anchor of treatment programs in most countries. While the DOTS regimens have a potential of curing 100% of new cases in program conditions, a success rate of over 85% is acceptable.
The DOTS strategy includes a strong political commitment, uninterrupted supply of anti-TB drugs of assured quality and administration of the drugs under direct observation, provision of diagnostic facilities for sputum smear examination, and standardized documentation and reporting systems. Nearly all Asian countries have adopted the DOTS strategy in their National TB Control Programs and have seen some decline in the incidence of TB in their countries since the introduction of DOTS (World Health Organization 2007a).
Abstract
Due to waning immunity following primary immunization with COVID-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike ...protein vaccine) in adults primed with viral vector and inactivated vaccines. In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with two doses of ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine (homologous booster of ChAdOx1 nCoV-19 or BBV152). Anti-S IgG and neutralizing antibodies (nAbs) were assessed at days 1, 29, and 181. Non-inferiority (NI) of SII-NVX-CoV2373 to the control vaccine was assessed based on the ratio of geometric mean ELISA units (GMEU) of anti-S IgG and geometric mean titers (GMT) of nAbs (NI margin > 0.67) as well as seroresponse (≥ 2 fold-rise in titers) (NI margin −10%) at day 29. Safety was assessed throughout the study period. In both the ChAdOx1 nCoV-19 prime and BBV152 prime cohorts, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 prime cohort, the GMEU ratio was 2.05 (95% CI 1.73, 2.43) and the GMT ratio was 1.89 (95% CI 1.55, 2.32) whereas the difference in the proportion of seroresponse was 49.32% (95% CI 36.49, 60.45) for anti-S IgG and 15% (95% CI 5.65, 25.05) for nAbs on day 29. In the BBV152 prime cohort, the GMEU ratio was 5.12 (95% CI 4.20, 6.24) and the GMT ratio was 4.80 (95% CI 3.76, 6.12) whereas the difference in the proportion of seroresponse was 74.08% (95% CI 63.24, 82.17) for anti-S IgG and 24.71% (95% CI 16.26, 34.62) for nAbs on day 29. The non-inferiority of SII-NVX-CoV2373 booster to the control vaccine for each prime cohort was met. SII-NVX-CoV2373 booster showed significantly higher immune responses than BBV152 homologous booster. On day 181, seroresponse rates were ≥ 70% in all the groups for both nAbs and anti-S IgG. Solicited adverse events reported were transient and mostly mild in severity in all the groups. No causally related SAE was reported. SII-NVX-CoV2373 as a heterologous booster induced non-inferior immune responses as compared to homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters. The vaccine was also safe and well tolerated.
Background & objectives: India has been reporting the cases of coronavirus disease 2019 (COVID-19) since January 30, 2020. The Indian Council of Medical Research (ICMR) formulated and established ...laboratory surveillance for COVID-19. In this study, an analysis of the surveillance data was done to describe the testing performance and descriptive epidemiology of COVID-19 cases by time, place and person.
Methods: The data were extracted from January 22 to April 30, 2020. The frequencies of testing performance were described over time and by place. We described cases by time (epidemic curve by date of specimen collection; seven-day moving average), place (area map) and person (attack rate by age, sex and contact status), and trends were represented along with public health measures and events.
Results: Between January 22 and April 30, 2020, a total of 1,021,518 individuals were tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Testing increased from about 250 individuals per day in the beginning of March to 50,000 specimens per day by the end of April 2020. Overall, 40,184 (3.9%) tests were reported positive. The proportion of positive cases was highest among symptomatic and asymptomatic contacts, 2-3-fold higher than among those with severe acute respiratory infection, or those with an international travel history or healthcare workers. The attack rate (per million) by age was highest among those aged 50-69 yr (63.3) and was lowest among those under 10 yr (6.1). The attack rate was higher among males (41.6) than females (24.3). The secondary attack rate was 6.0 per cent. Overall, 99.0 per cent of 736 districts reported testing and 71.1 per cent reported COVID-19 cases.
Interpretation & conclusions: The coverage and frequency of ICMR's laboratory surveillance for SARS-CoV-2 improved over time. COVID-19 was reported from most parts of India, and the attack rate was more among men and the elderly and common among close contacts. Analysis of the data indicates that for further insight, additional surveillance tools and strategies at the national and sub-national levels are needed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
HIV testing in India Tripathy, Srikanth; Pereira, Michael; Tripathy, Sriram Prasad
Clinics in laboratory medicine,
06/2012, Letnik:
32, Številka:
2
Journal Article
Recenzirano
The National AIDS Control Organization (NACO) has initiated programs for HIV/AIDS control in India. Algorithms for HIV testing have been developed for India. NACO programs have resulted in HIV ...situation improving over the last decade.
Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated ...in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13–22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.
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