BackgroundThe estimated number of people living with HIV (PLHIV) in India in 2023 is 2.54 million (range 2.16-3.03 million). With the initiation of antiretroviral therapy (ART) and the “Test and Treat” policy, the life expectancy of PLHIV on ART has substantially increased, consequently leading to a higher rate of comorbidities among PLHIV. The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2025 targets aim for about 90% of PLHIV to have access to integrated and comprehensive health care services, with a concerted effort to reach the End of AIDS by 2030. Hence, the National Integrated Bio-Behavioral Surveillance (IBBS) among PLHIV (IBBS-PLHIV) has been implemented for the first time in India to establish a baseline understanding of the prevalence of sexually transmitted infections (STIs), noncommunicable diseases (NCDs), and related risk behaviors among PLHIV. ObjectiveThe primary aim of IBBS-PLHIV is to estimate the levels of HIV-related risk behaviors and the prevalence of other STIs and NCDs among PLHIV. The specific objectives are identifying the levels of HIV-related sexual and injecting risk behaviors; estimating the prevalence of STIs such as syphilis, hepatitis B virus, and hepatitis C virus; estimating the prevalence of NCDs such as diabetes and hypertension; understanding the lifestyle and behavioral risks associated with NCDs; and assessing the levels of violence, stigma, and discrimination experienced by PLHIV. MethodsIBBS-PLHIV will be a cross-sectional, biennial surveillance among PLHIV aged 15 years or older. The first round will be implemented at 120 ART centers across 28 states, accounting for approximately 95% of the total estimated PLHIV. Consenting, eligible PLHIV will be recruited through consecutive sampling. The overall sample size at each ART center is approximately 225, and the surveillance period is 3 months. Behavioral data on demographics, reproductive and sexual health, lifestyle and sexual behaviors, stigma, and discrimination will be collected. Blood samples will also be collected to test for STIs and NCDs. ResultsIBBS-PLHIV was initiated on January 1, 2024, in a phased manner. Data collection was carried out over 3 months and completed by June 2024 across all 120 sites. A total of 25,257 PLHIV were recruited for the surveillance, including 11,921 males, 11,855 females, and 1481 hijra/transgender individuals. Data entry, followed by data matching and validation of all records, was completed in December 2024. The data are currently being analyzed, and the final findings are expected to be disseminated by December 2025. ConclusionsData collected through IBBS-PLHIV will help monitor the levels of HIV-related sexual and injecting risk behaviors among PLHIV. Additionally, it will provide estimates of the prevalence of NCD comorbidities and STI coinfections such as diabetes, hypertension, syphilis, and viral hepatitis. These findings will serve as a baseline and are expected to offer valuable insights for facilitating comprehensive HIV care and management through the effective integration of HIV and broader health service delivery. International Registered Report Identifier (IRRID)DERR1-10.2196/58252

BackgroundThis study was conducted to assess the prevalence of HIV and its associated risk factors among people who inject drugs in the four states of Central Zone of India (Bihar, Delhi, Uttar Pradesh and Uttarakhand), based on the data collected during the 17th round of HIV Sentinel Surveillance (HSS) during January to March, 2020.MethodsThe data was used from the 17th round of HSS which was collected through a paper-based survey among participants who were identified as people who inject drugs (PWIDs), followed by blood sample collection. Random sampling method was used to identify 250 PWIDs from each sentinel site.ResultsThe key demographic findings show that 60.1% of the participants were of age >=30 years and primarily urban residents (84.5%). Most participants have been tested for HIV previously (97.5%). With almost two-thirds of the participants injecting drugs daily, 89.5% of them reported to have used sterile needles each time. One-third of the participants had avoided health care services due to stigma and discrimination and they are significantly at higher odds of being HIV seropositive (1.83 times).ConclusionsThe study highlights the risk behaviour association with higher odds of being HIV seropositive were high risk occupation, sharing of needles, PWIDs on OST therapy, HIV testing and avoidance of healthcare services - due to stigma. Better programmatic approach is needed to protect the PWIDs.

India has intensified efforts towards elimination of vertical transmission of HIV (EVTH) as part of National AIDS and STD Control Programme-V (NACP-V). We present the progress in achieving NACP-V's EVTH goal as of year 2023-24. We analysed the 2023 state level data using Spectrum model in 2023 to measure the coverage of anti-retroviral treatment among pregnant women, annual paediatric HIV case incidence rate and final vertical transmission rate. UNAIDS and WHO definitions for these indicators were used. In 2023, around 2350 new paediatric infections were estimated by vertical transmission. However, 44% of these transmissions resulted from incident HIV infections among pregnant and breastfeeding women. Overall, paediatric HIV incidence per 100,000 live births decreased from 25.2 (14.7-46.6) in 2019 to 10.4 (6.1-19.3) in 2023. During the same reference period, final vertical transmission rate (inclusive of breastfeeding period) decreased from 25.28% (17.06-37.99) in 2019 to 11.75% (7.93-17.66) in 2023. The 2023 India HIV estimates, using recent data and global modelling tools, highlighted progress in eliminating vertical transmission of HIV. Early identification of HIV-positive mothers and starting them on lifelong ART is crucial. Additionally, generating local evidence is needed on interventions like safe practices, repeat testing, and feeding practices to inform policy decisions.

Background & objectives Only a few studies to date have described how violence victimisation, incarceration experience, and needle/syringe sharing synergistically interact to increase HIV risk among people who inject drugs (PWID) in India. Methods We analysed cross-sectional data on 19,902 men who inject drugs, recruited in the 2014/15 Integrated Bio-Behavioural Surveillance study of India's National AIDS Control Organisation. The outcome was human immunodeficiency virus (HIV) status. Syndemic exposures included past-year incarceration, past-year severe physical violence victimisation, and needle/syringe sharing. Regression models included covariates such as age, education, marital status, inconsistent condom use, HIV knowledge, and HIV programme exposure. We tested interactions using linear probability (additive scale) and logistic (multiplicate scale) regression models and examined causal pathways via path analysis. Results In this study, the HIV prevalence was found to be 9.9 per cent among men who inject drugs. We estimated substantial rates of needle/syringe sharing (17.8%), past-year incarceration (10.2%), and severe violence victimisation (3.8%). Among those incarcerated, 28 per cent injected drugs in prison. HIV seropositivity was associated with needle/syringe sharing [Adjusted odds ratio (aOR)=1.33; 95% Confidence interval (CI), 1.08-1.63], but not with violence victimisation or incarceration. In the logistic regression models, a significant two-way interaction was found between needle/syringe sharing and violence victimisation (semi-elasticity=0.65; 95% CI, 0.01-1.29) and a three-way interaction between needle/syringe sharing, violence victimisation, and incarceration (semi-elasticity=1.86; 95% CI, 0.51-3.20). In the linear probability regression models, we estimated a three-way additive interaction (relative excess risk of interaction=0.21; 95% CI, 0.03-0.28). Using path analysis, we estimated statistically significant indirect effects of both incarceration (b=0.02; 95% CI 0.01, 0.03) and severe violence victimisation (b=0.01; 95% CI, 0.008 to 0.02) on the HIV status, operating through their effects on needle/syringe sharing. Interpretation & conclusions Incarceration, violence victimisation, and needle/syringe sharing synergistically interacted to magnify HIV risk among men who inject drugs. These findings suggest the presence of a syndemic. Integrated interventions addressing these co-occurring conditions (e.g., needle/syringe exchange in prisons, violence prevention) may be necessary to effectively reduce HIV transmission among PWID in India.

India has the world's second-largest HIV burden. Key populations of female sex workers (FSW), men who have sex with men (MSM), hijra/transgender (H/TG) people, and people who inject drugs (PWID), are disproportionately affected by the HIV epidemic. A community-led programmatic mapping and population size estimation (PMPSE) was carried out in 651 districts of 32 States and Union Territories of India. The goal was to identify the hotspots, network operators, and estimate the size of key population groups. This involved documenting the known hotspots, visiting them for rapid field assessment through key informants'/ network operators interviews, and identifying additional hotspots/ network operators through the snow-balling approach from the existing hotspots. For each identified hotspot, network operator, and village, size of each key population group was estimated after adjusting for the duplications and overlaps. These estimates were then aggregated to arrive at district, State, and ultimately national-level estimates. PMPSE estimated a total of 9,95,499 (9,02,277-10,88,712) FSWs, 3,51,020 (3,13,860-3,88,175) MSM, 2,88,717 (2,53,024-3,24,407) PWIDs, and 96,193 (85,206-1,07,174) H/TG individuals. The number of FSWs per 1000 adult women in different States/Union Territories (UT) varied from 0.34 to 17.25; MSM estimates ranged from 0.07 to 7.35 per 1000 adult men, H/TG persons ranged from 0.03 to 2.75 per 1000 adult men, and PWIDs ranged from 0.01 to 31.30 per 1000 adult men. Additionally, approximately 14% of FSWs, 7% of MSM, and 8% of H/TG individuals were estimated to operate exclusively through network operators. The community-led PMPSE has updated the size estimates for FSWs, MSM, PWIDs, and H/TG individuals at a granular level. This approach has emphatically quantified the presence of network operators. The methodological simplicity of the present round of PMPSE is likely to encourage and facilitate its periodic implementation for better tracking of population level changes in HIV burden based on more reliable denominators.

One of the five high-level goals under Phase V of the National AIDS and STD Control Programme (NACP) of the Government of India is the elimination of vertical transmission of HIV. In this paper, we estimate the potential impact of maintaining and enhancing the anti-retroviral treatment under the NACP in terms of averting new infections and vertical transmission rates vis-à-vis no intervention scenario. We used India’s HIV Estimates 2022 models to create treatment coverage scenarios of no interventions, status quo, business as usual, on-track and fast-track scenarios from 2023 to 2030. Our analysis indicates that fast-tracking scale-up of treatment services would avert almost 41000 child infections from 2023 to 2030 leading to a vertical transmission rate of around 7.70% in 2030 vis-a-vis no interventions scenario. Higher and sustained ART coverage would not only take the country closer to the elimination goals but would also prevent thousands of vertical transmissions, thus bringing a lot of benefits to HIV-positive pregnant women and their families. Supported by efforts for the prevention of new infections in the general population, India is on track for the attainment of elimination of vertical transmission of HIV by 2030.

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.

Introduction: Adolescent female sex workers are at high risk of acquiring human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) infection. There was paucity of information regarding their sexual practices. The main objective of this study was to study the sexual behavior, condom use practices, and physical and sexual violence experienced by adolescent female sex workers (FSWs). Materials and Methods: This study was a secondary data analysis of the data collected during the nationwide IBBS 2014–15 survey. All adolescent FSWs aged 15 to 19 years were included in the analysis. The primary outcome variable was HIV serostatus, and independent variables included sexual behavior and condom use practices and socio-demographic variables. Descriptive analyses were performed to estimate the prevalence of independent variables. Ethical approval of the original IBBS study was obtained by the Ethics Committee of National AIDS Control Organization. Results: A total of 948 adolescent FSWs were included in the final analysis. The prevalence of HIV in adolescent FSWs was 1.2% [95% confidence interval, 0.1–1.9%]. The mean age [standard deviation (SD)] of FSWs was 18.2 (0.9) years. The mean (SD) age at first sexual intercourse was 15.6 (1.7) years, and the mean (SD) age of starting sex work was 16.6 (1.5) years. The majority of the FSWs (94%) had used condom during the last sexual intercourse with a commercial partner, and about one-thirds (66%) had consistently used condom with a commercial partner. About a quarter (26%) of the FSWs had anal intercourse with a commercial partner in the last 1 month. About one in five FSWs (21%) had experienced physical violence in the last 1 year. Conclusion: Almost one-third of FSWs had high-risk sexual behavior like multiple clients, anal intercourse, inconsistent condom use, and so on. These behaviors in turn increase their vulnerability to HIV infection.

Background The vulnerability of female sex workers (FSWs) to HIV infection increases if unprotected heterosexual anal intercourse (HAI) is practiced. Objectives To estimate the prevalence of HAI among FSWs, and associated factors, and prevalence of consistent condom use (CCU) during HAI and associated factors. Methods Analysis of cross-sectional data from nationwide biological and behavioural survey, conducted at 73 randomly selected domains with sample size of 27,000 in India. Results A total of 25,932 FSWs were included in the analysis, after excluding 1075 (3.9%) FSWs for which the data were incomplete. The prevalence of HAI was 29.9% (95% CI, 29.3, 30.4); The CCU during HAI in the last one month was 58.9%. Younger age at the start of sex work, use of mobile phone/internet for soliciting client, home as a place of sex work, consumption of alcohol/drug, and physical violence against FSWs were associated with higher odds of HAI. Frequent contact with outreach workers, awareness of sexually transmitted infection, and older age at the start of sex work was associated with CCU. Conclusion Prevalence of HAI was high among FSW in India. The national program could target those factors that reduce the odds of HAI and/or promote CCU.

PurposePrisoners are at a higher risk of HIV infection compared to the general population. The purpose of this study is to estimate the prevalence of HIV and related risk behaviours among inmates of the Central Prisons in four states of North India. Design/methodology/approachThe HIV sentinel surveillance was conducted in seven Central Prisons in four states of North India from February to April 2019. Four hundred inmates were included from each prison. The interviews were conducted at the Integrated Counselling and Testing Centre located within the prison premises. The Ethics Committee of the National AIDS Control Organization, New Delhi, granted ethical approval before the start of the surveillance. FindingsOverall, 2,721 inmates were enrolled in this study. The mean (SD) age was 38.9 (13.9) years. One-third of prison inmates had comprehensive knowledge about HIV/AIDS. The proportion of convict (54%) and undertrial (46%) inmates was almost equal. The overall prevalence of HIV infection among inmates was 0.96% (95% CI 0.65-1.40). The odds of being HIV positive were significantly higher in never married inmates, undertrials, inmates who were in the prison for more than three months to one year, inmates incarcerated for multiple times, inmates with history of injecting drug use and inmates with history of intercourse with a commercial sex worker. Originality/valueThe findings from the very first HIV sentinel surveillance in central prisons in North India have been presented in this paper. This has huge implications for future policy decisions.

INTRODUCTION:The hijra and transgender (H/TG) population in India is vulnerable to HIV/AIDS. India had instituted a targeted intervention (TI) program to reduce this vulnerability. We aimed to measure the effectiveness of the TI program for H/TG. MATERIALS AND METHODS:The National Integrated Behavioral and Biological Survey (IBBS) was carried out in 2014-15. H/TG data from IBBS was analyzed. Bivariate and multivariate logistic regression were used to calculate the unadjusted and adjusted odds ratios with 95% confidence interval. Condom use during the last sexual intercourse, and the consistent condom use in the last one month were considered as indicators of program effectiveness. The Propensity Score Matching (PSM) method was used to assess the effectiveness. RESULTS:We found that the participants who had received condoms from peer educator/outreach worker were 1.74 and 1.40 times more likely to use condoms in the last sexual intercourse (aOR: 1.74, CI: 1.35 - 2.26) and consistent condom use in the last one month (aOR: 1.40, CI: 1.12 - 1.74) respectively compared to the participants who did not receive the condom. The matched-samples estimate (i.e., average treatment effect on treated) for the condom use during the last sexual intercourse increased by 13.0%, i.e., 0.13 (CI; 0.08 - 0.18) and consistent condom use in the last one month increased by 5.0%, i.e., 0.05 (CI; 0.00 - 0.10) among those who had received condoms from the peer educator/outreach worker compared with those who had not received condom, respectively. CONCLUSIONS:The TI program intervention for H/TG was effective in reducing HIV risk behavior as evidenced by increase in use of condom during last sexual intercourse, and consistent condom use in the last one month.

Background: HIV prevalence among men who have sex with men (MSM) is 16.5 times higher than adult HIV prevalence. With a socio cultural context that demands marriage, a considerable proportion of MSM in India have female sexual partners and act as a bridge population. Stratified analysis of HIV risk factors among homosexual and bisexual MSM will be instrumental in identifying the high-risk MSM. We aim to identify the socio-demographic and behavioural factors associated with HIV risk among homosexual and bisexual MSM. Methods: Overall, 23081 MSM were enrolled in the IBBS conducted across India between October 2014 and November 2015. Data and blood samples were collected. Chi-square test, univariate and multivariable logistic regression methods were used in data analysis. Results: HIV prevalence was significantly higher among homosexual MSM than bisexual MSM. Older age, lesser education, being a sex worker, being married, living with a male or hijra partner, younger age at initiation of MSM behaviour, duration, injecting drugs, and having STI symptoms were associated with higher prevalence. The prevalence of new homosexual MSM was 11.4%. Nearly 75% of the bisexual MSM reported inconsistent condom usage with female partners. Conclusion: Interventions for early identification of new MSM and advocacy for safe sex with alternative preventive techniques are recommended. Keywords: HIV; Men who have sex with men; homosexual; bisexual; India.

People who inject drugs (PWID) are India's third-largest vulnerable population to human immunodeficiency virus (HIV) infection. PWID in India are confined to certain geographic locations and exhibit varying injecting and sexual risk behaviors, contributing considerably to increasing HIV trends in specific regions. Spatial heterogeneity in risk factors among vulnerable PWID influences HIV prevalence, transmission dynamics, and disease management. Stratified analysis of HIV prevalence based on risk behaviors and geographic locations of PWID will be instrumental in strategic interventions. To stratify the male PWID based on their risk behaviors in each state and determine the HIV prevalence for each stratum. The behavioral data and HIV prevalence of the national integrated biological and behavioural surveillance (IBBS), a nationwide cross-sectional community-based study conducted in 2014 to 2015, was analyzed. Data from 19,902 men who inject drugs across 53 domains in 29 states of India were included. Women who inject drugs were excluded at the time of IBBS, and hence PWID in this study refers to only men who inject drugs. PWID were categorized based on their risk profile, and the corresponding HIV prevalence for each state was determined. HIV prevalence was the highest (29.6%) in Uttar Pradesh, with a high prevalence of risk behaviors among PWID. High HIV prevalence ranging between 12.1% and 22.4% was observed in a few states in East and North-East India and most states in central and North India. Unsafe injecting and sexual practices were significantly (P < .05) associated with higher HIV prevalence and more significantly in National Capital Territory of Delhi (P < .001). Unsafe injecting practices among PWID were proportionally higher in Western and Central India, whereas unsafe sexual behaviors were widespread among most states. Unsafe sexual practices among male PWID were common. The high prevalence of unsafe injecting had significant HIV infection and transmission risks in Western and Central India. The results emphasize the need for stratified, region-specific interventions and combination approaches for harm reduction among PWID. Strengthening the measures that facilitate the reduction of high-risk behaviors, adoption of safe practices, and utilization of HIV services will positively impact HIV prevention measures among PWID.

Background & objectives: Female sex workers (FSWs) who inject drugs (FSW-IDs) have a higher risk of HIV infection and transmission. Understanding the socio-demographic characteristics and other risk behaviours among FSW-IDs will help in strengthening targeted interventions for HIV prevention and management. In the present study, the HIV prevalence, associated socio-demographic characteristics and risk behaviours among FSWs who injected drugs (FSW-IDs) and those who did not ID (FSW-NIDs) was determined in India. Methods: The national cross-sectional, community-based, integrated biological and behavioural surveillance was conducted in 2014-2015 at 73 randomly selected FSW domains across 28 States and Union Territories in India. The sample size was fixed at 400 for each domain, and a probability-based sampling method was followed. The data were analyzed by logistic regression methods. Results: Data from 27,007 FSWs were included in the analysis, of which 802 (3%) were FSW-IDs. HIV prevalence among FSW-IDs was significantly higher than that in FSW-NIDs (4.5 vs. 1.9%). Univariate analysis showed that factors significantly associated with higher HIV prevalence among FSW-IDs were older age, sex work as the only source of income, dissolved marriage, living with a sex worker, urban locality of sex work and consumption of alcohol or oral drugs. In multivariable analysis, factors such as older age of FSW-IDs (35 yr and above), having a dissolved marriage and sex work being the only source of income were observed to be independently and significantly associated with higher HIV prevalence. Interpretation & conclusions: Scaling up the HIV preventive interventions for FSW-IDs, such as facilitating awareness and improved access to needle and syringe exchange programme (NSEP) and opioid substitution therapy (OST), encouraging safe sex and injecting practices, educating on the harmful effects of alcohol and drugs and providing alternative vocation options to secure their financial needs are several strategies that may reduce HIV transmission among FSWs.

Transgender women globally are disproportionately burdened by HIV. Co-occurring epidemics of adverse psychosocial exposures accelerate HIV sexual risk, including among transgender women; however, studies using additive models fail to examine synergies among psychosocial conditions that define a syndemic. We examined the impact of synergistic interactions among 4 psychosocial exposures on condomless anal sex (CAS) among transgender women in India. A national probability-based sample of 4,607 HIV-negative transgender women completed the Indian Integrated Biological and Behavioural Surveillance survey, 2014-2015. We used linear probability regression and logistic regression to assess 2-, 3-, and 4-way interactions among 4 psychosocial exposures (physical violence, sexual violence, drug use, and alcohol use) on CAS. Overall, 27.3% reported physical and 22.3% sexual violence victimization (39.2% either physical or sexual violence), one-third (33.9%) reported frequent alcohol use and 11.5% illicit drug use. Physical violence was associated with twofold higher odds of CAS in the main effects model. Statistically significant two- and three-way interactions were identified, on both the multiplicative and the additive scales, between physical violence and drug use; physical and sexual violence; physical violence, sexual violence, and alcohol use; and physical violence, alcohol use and drug use. Physical and sexual violence victimization, and alcohol and drug use are highly prevalent and synergistically interact to increase CAS among HIV-negative transgender women in India. Targeted and integrated multilevel initiatives to improve the assessment of psychosocial comorbidities, to combat systemic transphobic violence, and to provide tailored, trauma-informed alcohol and substance use treatment services may reduce HIV risk among transgender women.

Background The Joint United Nations Programme on AIDS (UNAIDS) has emphasized on the incidence-prevalence ratio (IPR) and incidence-mortality ratio (IMR) to measure the progress in HIV epidemic control. In this paper, we describe the status of epidemic control in India and in various states in terms of UNAIDS’s recommended metrices. Method The National AIDS Control Programme (NACP) of India spearheads work on mathematical modelling to estimate HIV burden based on periodically conducted sentinel surveillance for providing guidance to program implementation and policymaking. Using the results of the latest round of HIV Estimations in 2019, IPR and IMR were calculated. Results National level IPR was 0.029 [0.022–0.037] in 2019 and ranged from 0.01 to 0.15 in various States and Union Territories (UTs). Corresponding Incidence-Mortality Ratio was at 0.881 [0.754–1.014] nationally and ranged between 0.20 and 12.90 across the States/UTs. Conclusions Based on UNAIDS recommended indicators for HIV epidemic control, namely IPR and IMR; national AIDS response in India appears on track. However, the program success is not uniform and significant heterogeneity as well as expanding epidemic was observed at the level of States or UTs. Reinforcing States/UTs specific and focused HIV prevention, testing and treatment initiatives may help in the attainment of 2030 Sustainable Development Goals of ending AIDS as a public health threat by 2030.

Initiation of DNA replication is mediated by the assembly of nucleoprotein complexes at cis-acting DNA sequences known as origins of replication. Recent studies in several systems show that accessory transcription factors accentuate origin utilization by multiple mechanisms. The remarkable similarities in the activities of accessory transcription factors at promoters and origins of replication suggest that transcription factors play a pivotal role in the regulation of chromosomal DNA synthesis in eukaryotic organisms.