Seropersistence of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine): 6-month follow-up of a randomized, controlled, observer-blind, phase 2/3 immuno-bridging study in Indian adults.

AZD1222 (ChAdOx1 nCoV-19) is a replication-deficient adenoviral vectored coronavirus disease-19 (COVID-19) vaccine that is manufactured as SII-ChAdOx1 nCoV-19 by the Serum Institute of India Pvt Ltd following technology transfer from Oxford University/AstraZeneca. The non-inferiority of SII-ChAdOx1 nCoV-19 with AZD1222 was previously demonstrated in an observer-blind, phase 2/3 immuno-bridging study (trial registration: CTRI/2020/08/027170). In this analysis of immunogenicity and safety data 6 months post first vaccination (Day 180), 1,601 participants were randomized 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (immunogenicity/reactogenicity cohort n = 401) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort n = 1,200). Immunogenicity was measured by anti-severe acute respiratory syndrome coronavirus 2 spike (anti-S) binding immunoglobulin G and neutralizing antibody (nAb) titers. A decline in anti-S titers was observed in both vaccine groups, albeit with a greater decline in SII-ChAdOx1 nCoV-19 vaccinees (geometric mean titer [GMT] ratio [95% confidence interval (CI) of SII-ChAdOx1 nCoV-19 to AZD1222]: 0.60 [0.41-0.87]). Consistent similar decreases in nAb titers were observed between vaccine groups (GMT ratio [95% CI]: 0.88 [0.44-1.73]). No cases of severe COVID-19 were reported following vaccination, while one case was observed in the placebo group. No causally related serious adverse events were reported through 180 days. No thromboembolic or autoimmune adverse events of special interest were reported. Collectively, these data illustrate that SII-ChAdOx1 nCoV-19 maintained a high level of immunogenicity 6 months post-vaccination. SII-ChAdOx1 nCoV-19 was safe and well tolerated.

A phase 2/3, participant-blind, observer-blind, randomised, controlled study to assess the safety and immunogenicity of SII-ChAdOx1 nCoV-19 (COVID-19 vaccine) in adults in India.

BACKGROUND: This phase 2/3 immunobridging study evaluated the safety and immunogenicity of the ChAdOx1 nCoV-19 Coronavirus Vaccine (Recombinant) (SII-ChAdOx1 nCoV-19), manufactured in India at the Serum Institute of India Pvt Ltd (SIIPL), following technology transfer from the AstraZeneca. METHODS: This participant-blind, observer-blind study randomised participants 3:1 to SII-ChAdOx1 nCoV-19 or AZD1222 (ChAdOx1 nCoV-19) (immunogenicity/reactogenicity cohort) and 3:1 to SII-ChAdOx1 nCoV-19 or placebo (safety cohort). The study participants were enrolled from 14 hospitals across India between August 25 and October 31, 2020. Two doses of study products were given 4 weeks apart. The primary objectives were to demonstrate non-inferiority of SII-ChAdOx1 nCoV-19 to AZD1222 in terms of geometric mean titre (GMT) ratio of anti-SARS-CoV-2 spike IgG antibodies 28 days after the second dose (defined as lower limit of 95% CI >0·67) and to determine the incidence of serious adverse events (SAEs) causally related to SII-ChAdOx1 nCoV-19. The anti-spike IgG response was assessed using a multiplexed electrochemiluminescence-based immunoassay. Safety follow-up continued until 6 months after first dose. Trial registration: CTRI/2020/08/027170. FINDINGS: 1601 participants were enrolled: 401 to the immunogenicity/reactogenicity cohort and 1200 to the safety cohort. After two doses, seroconversion rates for anti-spike IgG antibodies were more than 98·0% in both the groups. SII-ChAdOx1 nCoV-19 was non-inferior to AZD1222 (GMT ratio 0·98; 95% CI 0·78-1·23). SAEs were reported in ≤ 2·0% participants across the three groups; none were causally related. A total of 34 SARS-CoV-2 infections were reported; of which 6 occurred more than 2 weeks after the second dose; none were severe. INTERPRETATION: SII-ChAdOx1 nCoV-19 has a non-inferior immune response compared to AZD1222 and an acceptable safety/reactogenicity profile. Pharmacovigilance should be maintained to detect any safety signals. FUNDING: SIIPL funded the contract research organisation and laboratory costs, while the site costs were funded by the Indian Council of Medical Research. The study vaccines were supplied by SIIPL and AstraZeneca.

HIV-1 Drug Resistance Among Treatment-Naive Transgenders from India.

Transgenders (TGs) are highly affected by HIV with high prevalence of 3.14% in India. Since 2017, targeted preventive efforts have been initiated by the government and HIV-infected TGs are being provided the antiretroviral (ART) treatment. Information on the primary HIV drug resistance is crucial for appropriate treatment selection to curb further spread of HIV in this population. In this study, we analyzed HIV-1 pol gene sequences from 36 TGs for presence of drug resistance mutations. To our knowledge, this first study from India reports high-level primary drug resistance (13.8%) among the TG population. Mutations M184V, A98G, K103N, G190A, and Y318F associated with resistance to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitors were observed. All pol gene sequences revealed HIV-1 subtype C in all study TG. High-level HIV-1 drug resistance warrant nationwide larger studies on TGs to understand the level of primary ART drug resistance among this population.

Partial pol Sequences from Drug Naive HIV-2 Infected Individuals from Maharashtra, India.

HIV-2 is important due to its unique challenges in diagnosis, treatment, and drug resistance. The data on Indian HIV-2 pol gene as well as resistance to antiretroviral drugs are limited. Here we report sequence data of protease (PR) and reverse transcriptase (RT) genes from HIV-2 infected treatment naive individuals (N = 32) from Maharashtra, India. These sequences were found to be closely related to HIV-2 subtype A sequences from Guinea Bissau. We observed two unique residues at positions 14 and 70 in the PR region specific to Indian HIV-2. Mutations associated with resistance to RT and protease inhibitors were observed in 3 of 32 (9.37%) samples. To our knowledge, this is the first study from India to report drug resistance among treatment naive HIV-2 infected individuals. The results emphasize need for larger nationwide surveillance for HIV-2 drug resistance to better understand the primary drug resistance among HIV-2 infected individuals.

Cross-sectional study of virological failure and multinucleoside reverse transcriptase inhibitor resistance at 12 months of antiretroviral therapy in Western India.

The free antiretroviral therapy (ART) program in India has scaled up to register second largest number of people living with HIV/AIDS across the globe. To assess the effectiveness of current first-line regimen we estimated virological suppression on completion of 1 year of ART. The study describes the correlates of virological failure (VF) and multinucleoside reverse transcriptase inhibitor (NRTI) drug resistance mutations (DRMs).In this cross-sectional study conducted between June and August 2014, consecutive adults from 4 State sponsored ART clinics of western India were recruited for plasma viral load screening at 12 ±â€Š2 months of ART initiation. Individuals with plasma viral load >1000 copies/mL were selected for HIV drug resistance (HIVDR) genotyping. Logistic regression analyses were performed to assess factors associated with VF and multi-NRTI resistance mutations. Criteria adopted for multi-NRTI resistance mutation were either presence of K65R or 3 or more thymidine analog mutations (TAMs) or presence of M184V along with 2 TAMs.Of the 844 study participants, virological suppression at 1 year was achieved in 87.7% of individuals. Factors significantly associated with VF (P < 0.005) were 12 months CD4 count of ≤100 cells/µL (adjusted OR -7.11), low reported adherence (adjusted OR -4.44), and those living without any partner (adjusted OR -1.98). In patients with VF, the prevalence of non-nucleoside reverse transcriptase inhibitor (NNRTI) DRM (78.75%) were higher as compared to NRTI (58.75%). Multi-NRTI DRMs were present in 32.5% of sequences and were significantly associated with CD4 count of ≤100 cells/µL at baseline (adjusted OR -13.00) and TDF-based failing regimen (adjusted OR -20.43). Additionally, low reported adherence was negatively associated with multi-NRTI resistance (adjusted OR -0.11, P = 0.015). K65R mutation was significantly associated with tenofovir (TDF)-based failing regimen (P < 0.001).The study supports early linkage of HIV-infected individuals to the program for ART initiation, adherence improvement, and introduction of viral load monitoring. With recent introduction of TDF-based regimen, the emergence of K65R needs to be monitored closely among HIV-1 subtype C-infected Indian population.

Short Communication: Limited HIV Pretreatment Drug Resistance Among Adults Attending Free Antiretroviral Therapy Clinic of Pune, India.

In India, the roll out of the free antiretroviral therapy (ART) program completed a decade of its initiation in 2014. The success of first-line ART is influenced by prevalence of HIV pretreatment drug resistance (PDR) in the population. In this cross-sectional study, we sought to determine the prevalence of PDR among adults attending the state-sponsored free ART clinic in Pune in western India. Fifty-two individuals eligible for ART as per national guidelines with median CD4 cell count of 253 cells/mm(3) (inter quartile range: 149-326) were recruited between January 2014 and April 2015. Population-based sequencing of partial pol gene sequences from plasma specimen revealed predominant HIV-1 subtype C infection (96.15%) and presence of single-drug resistance mutations against non-nucleoside reverse transcriptase inhibitor in two sequences. The study supports the need for periodic surveillance, when offering PDR testing at individual level is not feasible.

Near Full-Length Genomic Characterization of a Novel CRF 01_AE/C Recombinant from Western India.

HIV is known for its genetic variability across the globe. The HIV epidemic in India is primarily driven by subtype C, although sporadic circulating and unique recombinant forms are also reported from a few metropolitan cities in which genotyping facilities are available. Here we report a novel CRF01_AE/C recombinant from a multicenter study on the effectiveness of antiretroviral therapy (ART), 12 months after its initiation. Our subject is a 32-year-old heterosexual female, a native of Pune city in western India. Identification and analyses of recombination breakpoints using jpHMM@Gobics and SimPlot bootscanning revealed six recombination breakpoints, indicating insertion of the CRF01_AE genome at three points in the backbone of subtype C. Both subtype C and CRF01_AE are commonly seen in the population at risk of heterosexual HIV transmission, thereby providing an opportunity for cocirculation and recombination. The emergence of a novel recombinant of CRF01_AE/C is indicative of the increasing genetic diversity of the HIV epidemic in India.

Emergence of NNRTI drug resistance mutations after single-dose nevirapine exposure in HIV type 1 subtype C-infected infants in India.

A feasibility study for providing single-dose nevirapine (SD-NVP) prophylaxis for prevention of mother-to-child transmission (PMTCT) of HIV infection provided an opportunity to study the emergence of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations as a result of single-dose administration. The study aimed at the detection of NNRTI drug resistance mutations arising as a result of SD-NVP. A total of 19 and 13 samples collected at 48 h and 2 months postpartum, respectively, from infants that were given SD-NVP were studied for the presence of NNRTI drug resistance mutations by PCR amplification and sequencing of the HIV-1 pol gene using HIV proviral DNA. The drug resistance mutational analysis of final sequences was carried out using the Stanford University HIV Drug Resistance database (http://hivdb.stanford.edu/hiv). Mutations associated with NNRTI drug resistance were observed in two (10.5%) and six (46.15%) samples at 48 h and at 2 months, respectively. K103N, one of the most common mutations, was not observed in any of the samples. The emergence of NVP resistance must be weighed against the simplicity, efficacy, and cost effectiveness of SD-NVP prophylaxis in PMTCT settings in developing countries.

Subtype B and subtype C HIV type 1 recombinants in the northeastern state of Manipur, India.

The predominant HIV-1 strain circulating in India is subtype C. However, subtype A and B strains of HIV-1 have also been reported in India. In 1999, the first A/C recombinant strain was reported from Pune in India. Intravenous drug users (IVDUs) from the northeastern region of India have a high HIV-1 seroprevalence. Studies carried out in intravenous drug users in the northeastern region of India have shown that HIV-1 subtype C is the predominant strain infecting IVDUs. Fourteen blood samples were collected from HIV-1-infected individuals from the northeastern region of India and screened by env and gag heteroduplex mobility assays (HMA). Where the env and gag HMA results from a sample yielded different subtypes, sequencing of env and gag PCR products was carried out to confirm the presence of HIV-1 recombinants. Of the 14 samples subtyped, nine samples belonged HIV-1 subtype C (gag C/env C), one to HIV-1 subtype B (gag B/env B), and the remaining were B/C recombinants (gag C/env B). This is the first report of HIV-1 B/C recombinants from India.