Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.

BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

Clinico-epidemiological presentations and management of Nipah virus infection during the outbreak in Kozhikode district, Kerala state, India 2023.

India experienced its sixth Nipah virus (NiV) outbreak in September 2023 in the Kozhikode district of Kerala state. The NiV is primarily transmitted by spillover events from infected bats followed by human-to-human transmission. The clinical specimens were screened using real-time RT-PCR, and positive specimens were further characterized using next-generation sequencing. We describe here an in-depth clinical presentation and management of NiV-confirmed cases and outbreak containment activities. The current outbreak reported a total of six cases with two deaths, with a case fatality ratio of 33.33%. The cases had a mixed presentation of acute respiratory distress syndrome and encephalitis syndrome. Fever was a persistent presentation in all the cases. The Nipah viral RNA was detected in clinical specimens until the post-onset day of illness (POD) 14, with viral load in the range of 1.7-3.3 × 104 viral RNA copies/mL. The genomic analysis showed that the sequences from the current outbreak clustered into the Indian clade similar to the 2018 and 2019 outbreaks. This study highlights the vigilance of the health system to detect and effectively manage the clustering of cases with clinical presentations similar to NiV, which led to early detection and containment activities.

Neutralizing antibody responses to SARS-CoV-2 Omicron variants: Post six months following two-dose & three-dose vaccination of ChAdOx1 nCoV-19 or BBV152.

BACKGROUND OBJECTIVES: The Omicron sub-lineages are known to have higher infectivity, immune escape and lower virulence. During December 2022 - January 2023 and March - April 2023, India witnessed increased SARS-CoV-2 infections, mostly due to newer Omicron sub-lineages. With this unprecedented rise in cases, we assessed the neutralization potential of individuals vaccinated with ChAdOx1 nCoV (Covishield) and BBV152 (Covaxin) against emerging Omicron sub-lineages. METHODS: Neutralizing antibody responses were measured in the sera collected from individuals six months post-two doses (n=88) of Covishield (n=44) or Covaxin (n=44) and post-three doses (n=102) of Covishield (n=46) or Covaxin (n=56) booster dose against prototype B.1 strain, lineages of Omicron; XBB.1, BQ.1, BA.5.2 and BF.7. RESULTS: The sera of individuals collected six months after the two-dose and the three-dose demonstrated neutralizing activity against all variants. The neutralizing antibody (NAbs) level was highest against the prototype B.1 strain, followed by BA5.2 (5-6 fold lower), BF.7 (11-12 fold lower), BQ.1 (12 fold lower) and XBB.1 (18-22 fold lower). INTERPRETATION CONCLUSIONS: Persistence of NAb responses was comparable in individuals with two- and three-dose groups post six months of vaccination. Among the Omicron sub-variants, XBB.1 showed marked neutralization escape, thus pointing towards an eventual immune escape, which may cause more infections. Further, the correlation of study data with complete clinical profile of the participants along with observations for cell-mediated immunity may provide a clear picture for the sustained protection due to three-dose vaccination as well as hybrid immunity against the newer variants.

Age-Specific Prevalence of Anal and Cervical Human Papillomavirus Infection and High-Grade Lesions in 11 177 Women by Human Immunodeficiency Virus Status: A Collaborative Pooled Analysis of 26 Studies.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15-24 years to 1.0% at ≥55 years; ptrend = 0.0026) and cervix (7.4% to 1.7%; ptrend < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; ptrend = 0.0035) but not anus (11.5% to 13.9%; ptrend = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (ptrend = 0.0005) and WWH (ptrend = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Pregnancy rates and clinical outcomes among women living with HIV enrolled in HPTN 052.

HPTN 052 was a multi-country clinical trial of cART for preventing heterosexual HIV-1 transmission. The study allowed participation of pregnant women and provided access to cART and contraceptives. We explored associations between pregnancy and clinical measures of HIV disease stage and progression. Of 869 women followed for 5.70 (SD = 1.62) years, 94.7% were married/cohabitating, 96% initiated cART, and 76.3% had >2 past pregnancies. Of 337 women who experienced pregnancy, 89.3% were from countries with lower contraceptive coverage, 56.1% first started cART with PI-based regimens and 57.6% were 25-34 years old. Mean cART duration and condom use were similar among pregnant and nonpregnant individuals. Adjusting for confounders, viral load suppression (VLS) was not (aHR(CI) = 0.82(0.61, 1.08)) and CD4 was slightly associated with decreased rates of first pregnancy over time (aHR(CI) = 0.9(0.84, 0.95)); baseline VLS was associated with increased (aRR(CI) = 2.48(1.71, 3.59)) and baseline CD4 was slightly associated with decreased number of pregnancies (aRR(CI) = 0.9(0.85,0.96)) over study duration. Partner seroconversion was univariably associated with higher rates of first pregnancy (HR(CI) = 2.02(1.32,3.07)). Despite a background of higher maternal morbidity and mortality rates, our findings suggest that becoming pregnant does not pose a threat to maternal health in women with HIV when there is access to medical care and antiretroviral treatment.

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282.

BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.

Comparison of prevention of parent-to-child HIV transmission programme & national biennial HIV sentinel surveillance data for tracking HIV epidemic in India.

Background & objectives: HIV sentinel surveillance (HSS) among antenatal women in India has been used to track the epidemic for many years. However, reliable tracking at the local level is not possible as ANC sentinel sites are limited in number and cover a smaller sample size at each site. Prevention of parent-to-child-transmission (PPTCT) programme data has a potential advantage due to better geographical coverage, which could provide more precise HIV case estimates; therefore, we compared HSS ANC data with PPTCT programme data for HIV tracking. Methods: Out of the 499 surveillance sites, where HSS and PPTCT programme was being conducted in 2015, 210 sites (140 urban and 70 rural) were selected using a stratified random sampling method. HSS (n=72,981) and PPTCT (n=112,832) data records were linked confidentially. The sociodemographic characteristics of HSS and PPTCT attendees were compared. HIV prevalence from HSS ANC was compared with the PPTCT programme data using Chi-square test. State- and site-level correlation of HIV prevalence was also done. Concordance between HSS and PPTCT HIV positivity was estimated using kappa statistics. Results: The age distribution of HSS and PPTCT attendees was similar (range: 23 to 27 yr); however, HSS ANC participants were better educated, whereas PPTCT recorded a higher proportion of homemakers. The correlation of HIV prevalence between HSS and PPTCT was high (r=0.9) at the State level and moderate at the site level (r=0.7). The HIV positivity agreement between HSS ANC and PPTCT was good (kappa=0.633). A similar prevalence was reported across 26 States, whereas PPTCT had a significantly lower prevalence than HSS in three States where PPTCT coverage was low. Overall HIV prevalence was 0.31 per cent in HSS and 0.22 per cent in PPTCT (P<0.001). Interpretation & conclusions: High-quality PPTCT programme data can provide reliable HIV trends in India. An operational framework for PPTCT-based surveillance should be pilot-tested in a phased manner before replacing HSS with PPTCT.

Findings from the 2017 HIV estimation round & trend analysis of key indicators 2010-2017: Evidence for prioritising HIV/AIDS programme in India.

Background & objectives: The National AIDS Control Organisation (NACO) and the ICMR-National Institute of Medical Statistics, the nodal agency for conducting HIV estimations in India, have been generating HIV estimates regularly since 2003. The objective of this study was to describe India's biennial HIV estimation 2017 process, data inputs, tool, methodology and epidemiological assumptions used to generate the HIV estimates and trends of key indicators for 2010-2017 at national and State/Union Territory levels. Methods: Demographic Projection (DemProj) and AIDS Impact Modules (AIM) of Spectrum 5.63 software recommended by the United Nations Programme on HIV and AIDS Global Reference Group on HIV Estimates, Modelling and Projections, were used for generating HIV estimations on key indicators. HIV sentinel surveillance, epidemiological and programme data were entered into Estimation Projection Package (EPP), and curve fitting was done using EPP classic model. Finally, calibration was done using the State HIV prevalence of two rounds of National Family Health Survey (NFHS) -3 and -4 and Integrated Biological and Behavioural Surveillance (IBBS), 2014-2015. Results: The national adult prevalence of HIV was estimated to be 0.22 per cent in 2017. Mizoram, Manipur and Nagaland had the highest prevalence over one per cent. An estimated 2.1 million people were living with HIV in 2017, with Maharashtra estimated to have the highest number. Of the 88 thousand annual new HIV infections estimated nationally in 2017, Telangana accounted for the largest share. HIV incidence was found to be higher among key population groups, especially people who inject drugs. The annual AIDS-related deaths were estimated to be 69 thousand nationally. For all indicators, geographic variation in levels and trends between States existed. Interpretation & conclusions: With a slow decline in annual new HIV infections by only 27 per cent from 2010 to 2017 against the national target of 75 per cent by 2020, the national target to end AIDS by 2030 may be missed; although at the sub-national level some States have made better progress to reduce new HIV infection. It calls for reinforcement of HIV prevention, diagnosis and treatment efforts by geographical regions and population groups.

Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

BACKGROUND: An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. METHODS: We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. RESULTS: Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. CONCLUSIONS: The early initiation of ART led to a sustained decrease in genetically linked HIV-1 infections in sexual partners. (Funded by the National Institute of Allergy and Infectious Diseases; HPTN 052 ClinicalTrials.gov number, NCT00074581 .).

Evaluation of key survey components of bio-behavioral surveillance among HIV high-risk subpopulation in Western India.

BACKGROUND: High-quality data are of prime importance in any health survey because survey data are considered as a gold standard for nationally representative data. The quality of data collection largely depends on the design of the questionnaire, training, and skills of the interviewer. OBJECTIVES: In the present study, we tried to evaluate three key components, such as questionnaire design, human resource and training of the field staff for Integrated Biological and Behavioural Surveillance carried out among the HIV high-risk subpopulation. METHODS: A mixed-methods approach was used. Qualitative and quantitative data collection was carried out in the year 2015 with cross-sectional survey design in western states of India. The in-depth interviews of 10 stakeholders, structured interviews of the survey respondents (n = 560), and field investigators (n = 71) were conducted. Data triangulation was used to find out the concurrence of the qualitative and quantitative data. RESULTS: Comprehensive and standardized survey questionnaire, structured training agenda, and strategic preparation for recruiting human resources were the overall strengths of the survey. However, during the implementation of the survey, there were some difficulties reported in data collection process. Overall, the respondents and investigators felt that the questionnaire was long and exhaustive. Difficulties were faced while collecting data on sexual history. The field staffs were not adequately experienced to work with sensitive population. CONCLUSIONS: In order to have accurate, reliable data, especially on sexual behavior; emphasis should be given on simple questionnaire with the use of community-friendly language, skilled and experienced interviewers for data collection, and extensive field training.

Higher expression of human telomerase reverse transcriptase in productively-infected CD4 cells possibly indicates a mechanism for persistence of the virus in HIV infection.

Mechanisms involved in survival of productively-infected memory CD4+cells after initial antigenic stimulation and their subsequent reversion to the resting state are critical for the development of a predominant replication-competent HIV reservoir. These mechanisms may also counter their elimination after HIV reactivation through latency-reversing agents (LRA). Thus, their evaluation is critical when using an appropriate HIV latency model that recapitulates the predominant replication-competent HIV reservoir to develop strategies for HIV eradication. The model for evaluating the possible survival mechanisms after T cell receptor (TCR) stimulation was developed by infecting memory CD4+cells with an HIV-1C primary isolate and cytokine secretion and gene expression patterns determined. Infected cells showed compromised functionality as evident from 6.8-fold lower secretion of IL-2 than from uninfected control cells. After TCR stimulation, the infected cells showed significantly higher fold increases in CD27 and CCR5 and smaller increases in CD5 mRNA over baseline values. Because CD27 expression may influence telomerase activity through AKT phosphorylation, CD27, human telomerase reverse transcriptase (hTERT) and pAKT expression in productively-infected cells from HIV-infected patients was evaluated by flow cytometry. HIV harbored in memory CD4+ cells was reactivated by HIV-1 envelope peptides, which have been shown to act as effective LRA. P24+CD4+cell showed significantly higher expression of CD27, hTERT and pAKT than P24-CD4+cells. These findings indicate compromised functionality of HIV-infected cells after TCR stimulation, which may interfere with their elimination by the immune system. They also indicate that pAKT and hTERT induction are possible survival mechanisms of productively-infected CD4+cells.

Cost-effectiveness of HIV treatment as prevention in serodiscordant couples.

BACKGROUND: The cost-effectiveness of early antiretroviral therapy (ART) in persons infected with human immunodeficiency virus (HIV) in serodiscordant couples is not known. Using a computer simulation of the progression of HIV infection and data from the HIV Prevention Trials Network 052 study, we projected the cost-effectiveness of early ART for such persons. METHODS: For HIV-infected partners in serodiscordant couples in South Africa and India, we compared the early initiation of ART with delayed ART. Five-year and lifetime outcomes included cumulative HIV transmissions, life-years, costs, and cost-effectiveness. We classified early ART as very cost-effective if its incremental cost-effectiveness ratio was less than the annual per capita gross domestic product (GDP; $8,100 in South Africa and $1,500 in India), as cost-effective if the ratio was less than three times the GDP, and as cost-saving if it resulted in a decrease in total costs and an increase in life-years, as compared with delayed ART. RESULTS: In South Africa, early ART prevented opportunistic diseases and was cost-saving over a 5-year period; over a lifetime, it was very cost-effective ($590 per life-year saved). In India, early ART was cost-effective ($1,800 per life-year saved) over a 5-year period and very cost-effective ($530 per life-year saved) over a lifetime. In both countries, early ART prevented HIV transmission over short periods, but longer survival attenuated this effect; the main driver of life-years saved was a clinical benefit for treated patients. Early ART remained very cost-effective over a lifetime under most modeled assumptions in the two countries. CONCLUSIONS: In South Africa, early ART was cost-saving over a 5-year period. In both South Africa and India, early ART was projected to be very cost-effective over a lifetime. With individual, public health, and economic benefits, there is a compelling case for early ART for serodiscordant couples in resource-limited settings. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Prevention of HIV-1 infection with early antiretroviral therapy.

BACKGROUND: Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. METHODS: In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. RESULTS: As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01). CONCLUSIONS: The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).

Monocyte to lymphocyte ratio and hemoglobin level to predict tuberculosis after antiretroviral therapy initiation.

OBJECTIVE: To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation. DESIGN: Multicenter, retrospective cohort study. METHODS: We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS). We assessed the utility of MLR, anemia severity and in combination, for predicting TB in the first year after ART. Cox regression was used to assess associations of MLR and anemia with incident TB. Harrell's C index was used to describe single model discrimination. RESULTS: A total of 1455 participants with a median age of 34 [interquartile range (IQR) 29, 41] were included. Fifty-four participants were diagnosed with TB. The hazard ratio (HR) for incident TB was 1.77 [95% confidence interval (CI) 1.01-3.07]; P  = 0.04 for those with MLR ≥0.23. The HR for mild/mod anemia was 3.35 (95% CI 1.78-6.29; P  < 0.001) and 18.16 (95% CI 5.17-63.77; P  < 0.001) for severe anemia. After combining parameters, there were increases in adjusted HR (aHR) for MLR ≥0.23 to 1.83 (95% CI 1.05-3.18), and degrees of anemia to 3.38 (95% CI 1.80-6.35) for mild/mod anemia and 19.09 (95% CI 5.43-67.12) for severe anemia. CONCLUSIONS: MLR and hemoglobin levels which are available in routine HIV care can be used at ART initiation for identifying patients at high risk of developing TB disease to guide diagnostic and management decisions.

WHO global research priorities for sexually transmitted infections.

Sexually transmitted infections (STIs) are widespread worldwide and negatively affect sexual and reproductive health. Gaps in evidence and in available tools have long hindered STI programmes and policies, particularly in resource-limited settings. In 2022, WHO initiated a research prioritisation process to identify the most important STI research areas to address the global public health need. Using an adapted Child Health and Nutrition Research Initiative methodology including two global stakeholder surveys, the process identified 40 priority STI research needs. The top priorities centred on developing and implementing affordable, feasible, rapid point-of-care STI diagnostic tests and new treatments, especially for gonorrhoea, chlamydia, and syphilis; designing new multipurpose prevention technologies and vaccines for STIs; and collecting improved STI epidemiologic data on both infection and disease outcomes. The priorities also included innovative programmatic approaches, such as new STI communication and partner management strategies. An additional six research areas related to mpox (formerly known as monkeypox) reflect the need for STI-related research during disease outbreaks where sexual transmission can have a key role. These STI research priorities provide a call to action for focus, investment, and innovation to address existing roadblocks in STI prevention, control, and management to advance sexual and reproductive health and wellbeing for all.

Acceptability, usability, and willingness to pay for HIV self-test kits distributed through community-based, PLHIV network-led and private practitioners models in India: Results from the STAR III Initiative.

INTRODUCTION: HIV self-testing (HIVST) has been shown to increase the uptake of HIV testing and help achieve the UNAIDS 95-95-95 targets. This study assessed the acceptability, usability (ease of use and result interpretation) and the willingness to pay for HIVST kits distributed through three distribution models, namely the community-based, PLHIV network-led and private practitioners models, in India. METHODS: This cross-sectional study was implemented across 14 states in India between September 2021 and June 2022. All participants could choose between blood-based or oral-fluid-based test kits. Participants were shown a test-kit usage demonstration video, and pre- and post-test counselling was provided for all. Participants were followed-up after testing, and if reported reactive, were further supported for linkage to confirmatory testing and antiretroviral therapy (ART) initiation. RESULTS: Among the 90,605 participants found eligible, 88,080 (97%) accepted an HIVST kit. Among the 87,976 who reported using an HIVST kit, 45,207 (51%) preferred a blood-based kit, and 42,120 (48%) reported testing for the first time. For future testing, 77,064 (88%) reported preferring HIVST over other HIV testing methods. Among those who used the kit, 83,308 (95%) found the kit easy to use, and 83,237 (95%) reported that the test results were easy to interpret. Among those who preferred HIVST for future use, 52,136 (69%) were willing to pay for the kit, with 35,854 (69%) of those willing to pay less than US$ 1.20. Only one instance of social harm was reported, with a participant reporting suicidal tendencies due to discord with their partner. Out of 328 participants (0.4%) who tested reactive with HIVST, 291 (89%) were linked to confirmatory testing; of these, 254 were confirmed HIV positive, and 216 (85%) successfully initiated ART. CONCLUSIONS: Overall, we report that nearly all participants were willing to accept HIVST, found the test kits easy to use and interpret, and about two-thirds were willing to pay for HIVST. Given the high levels of acceptance and the ability to reach a large proportion of first-time testers, HIVST in India could contribute to achieving the UNAIDS first 95 and ending the HIV epidemic.

A protocol for feasibility of plasma based GeneXpert platform and Dried Blood Spot (DBS) based Abbott platform for HIV-1 viral load testing among the people living with HIV attending ART centers in India.

BACKGROUND: HIV-1 Viral load (VL) measures efficiency of the antiretroviral therapy (ART) after treatment initiation and helps to diagnose virological failures at an early stage. Current VL assays require sophisticated laboratory facilities. As well as there are other challenges pertaining to insufficient laboratory access, cold-chain management and sample transportation. Hence the number of HIV-1 VL testing laboratories is inadequate in the resource limited settings. The revised national tuberculosis elimination programme (NTEP) in India has developed a vast network of point of care (PoC) testing facilities for diagnosis of tuberculosis and several GeneXpert platforms are functional under this programme. Both the GeneXpert HIV-1 assay and HIV-1 Abbott real time assay are comparable and GeneXpert HIV-1 assay can be used as PoC for HIV-1 Viral load testing. Also, the dried blood spot (DBS) as a sample type has been considered as a good option for HIV-1 VL testing in hard to reach areas. This protocol is therefore developed to assess the feasibility of integrating HIV-1 VL testing among people living with HIV (PLHIV) attending ART centres using the two public health models under the current programme: 1. HIV-1 VL testing using GeneXpert platform and plasma as a sample type, and 2. HIV-1 VL testing using Abbott m2000 platform and DBS as a sample type. METHODS: This ethically approved feasibility study will be implemented at two moderate to high burden ART centres where VL testing facility is not available in the town. Under Model-1, arrangements will be made to carry out VL testing on the adjacent GeneXpert facility and under Model-2, DBS will be prepared on site and couriered to identified viral load testing laboratories. In order to assess the feasibility, data will be collected on pretested questionnaire pertaining to number of samples tested for VL testing, number of samples tested for tuberculosis (TB) diagnosis and the turnaround time (TAT). In-depth interviews will be conducted among the service providers at ART centre and different laboratories for addressing any issues regarding the model implementation. RESULTS: The proportion of PLHIV tested for VL at ART centres, total TAT for both models including TAT for sample transportation, sample testing and receipt of results as well as proportion of sample rejections and reasons for the same, correlation coefficient between DBS based and plasma based VL testing will be estimated using various statistical tools. CONCLUSION: If found promising, these public health approaches will be helpful for the policy makers and program implementation in scaling up HIV-1 viral load testing within India.

HIV-1 exploits Hes-1 expression during pre-existing HPV-16 infection for cancer progression.

High Risk Human Papilloma Viruses (HR-HPV) persistently infect women with Human Immunodeficiency Virus-1 (HIV-1). HPV-16 escapes immune surveillance in HIV-1 positive women receiving combined antiretroviral therapy (cART). HIV-1 Tat and HPV E6/E7 proteins exploit Notch signaling. Notch-1, a developmentally conserved protein, influences cell fate from birth to death. Notch-1 and its downstream targets, Hes-1 and Hey-1 contribute to invasive and aggressive cancers. Cervical cancer cells utilize Notch-1 and hyper-express CXCR4, a co-receptor of HIV-1. Accumulating evidence shows that HIV-1 affects cell cycle progression in pre-existing HPV infection. Additionally, Tat binds Notch-1 receptor for activation and influences cell proliferation. Oncogenic viruses may interfere or converge together to favor tumor growth. The molecular dialogue during HIV-1/HPV-16+ co-infections in the context of Notch-1 signaling has not been explored thus far. This in vitro study was designed with cell lines (HPV-ve C33A and HPV-16+ CaSki) which were transfected with plasmids (pLEGFPN1 encoding HIV-1 Tat and pNL4-3 encoding HIV-1 [full HIV-1 genome]). HIV-1 Tat and HIV-1 inhibited Notch-1expression, with differential effects on EGFR. Notch-1 inhibition nullified Cyclin D expression with p21 induction and increased G2-M cell population in CaSki cells. On the contrary, HIV-1 infection shuts down p21 expression through interaction of Notch-1 downstream genes Hes-1-EGFR and Cyclin D for G2-M arrest, DDR response and cancer progression. This work lays foundations for future research and interventions, and therefore is necessary. Our results describe for the first time how HIV-1 Tat cancers have an aggressive nature due to the interplay between Notch-1 and EGFR signaling. Notch-1 inhibitor, DAPT used in organ cancer treatment may help rescue HIV-1 induced cancers. Graphical abstract: The illustration shows how HIV interacts with HPV-16 to induce Notch 1 suppression for cancer progression (Created with BioRender.com). Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00809-y.

Augmenting progress on the elimination of vertical transmissions of HIV in India: Insights from Spectrum-based HIV burden estimations.

The government of India has adopted the elimination of vertical transmission of HIV as one of the five high-level goals under phase V of the National AIDS and STD Control Programme (NACP). In this paper, we present the data from HIV estimations 2021 for India and select States detailing the progress as well as the attributable causes for vertical transmissions. The NACP spearheads work on mathematical modelling to estimate HIV burden based on the periodically conducted sentinel surveillance for guiding program implementation and policymaking. Using the results of the latest round of HIV Estimations in 2021, we analysed the mother-to-child transmission (MTCT) during the perinatal and postnatal (breastfeeding) period. In 2021, overall, around 5,000 [3,000-7,800] vertical transmissions were estimated nationally with 58% being perinatal infections and remaining during breastfeeding. MTCT at 6 weeks was around 12.95% [9.45-16.02] with the final transmission rate at 24.25% [18.50-29.50]. Overall, 57% of vertical transmissions were among HIV-positive mothers who did not receive ART during pregnancy or breastfeeding, 19% among mothers who dropped off ART during pregnancy or delivery, and 18% among mothers who were infected during pregnancy or breastfeeding. There were significant variations between States. Depending upon the States, the programme needs to focus on the intervention domains of timely engagement in antenatal care-HIV testing-ART initiation as well as programme retention and adherence support. Equally important would be strengthening the strategic information to generate related evidence for inputting India and State-specific parameters improving the MTCT-related modelled estimates.