Control of sexually transmitted infections and global elimination targets, South-East Asia Region.

The World Health Organization (WHO) set targets for a 90% reduction in the incidence of syphilis and gonorrhoea between 2018 and 2030. We review trends in sexually transmitted infections in the WHO South-East Asia Region to assess the feasibility of reaching these targets. Myanmar, Sri Lanka and Thailand reported 90% or greater reductions in the incidence or prevalence of syphilis and/or gonorrhoea between 1975 and 2005. Evidence suggests that smaller, more recent reductions in trends in sexually transmitted infections in India have driven regional declines. In other countries, sexually transmitted infections remain high or are increasing or data are not reliable enough to measure change. Sri Lanka and Thailand have strong control programmes for sexually transmitted infections that ensure universal access to services for these infections and targeted interventions in key populations. India and Myanmar have implemented targeted control efforts on a large scale. Other countries of the region have prioritized control of human immunodeficiency virus, and limited resources are available for other sexually transmitted infections. At national and subnational levels, data show rapid declines in sexually transmitted infections when targeted promotion of condom use and sexually transmitted infection services are scaled up to reach large numbers of sex workers. In contrast, recent outbreaks of sexually transmitted infections in underserved populations of men who have sex with men have been linked to rising trends in sexually transmitted infections in the region. A renewed and focused response to sexually transmitted infections in the region is needed to meet global elimination targets.

L'Organisation mondiale de la Santé (OMS) a fixé des objectifs pour réduire à 90% l'incidence de la syphilis et de la gonorrhée entre 2018 et 2030. Nous avons étudié les tendances en matière d'infections sexuellement transmissibles dans la Région d'Asie du Sud-Est de l'OMS afin d'évaluer la faisabilité de ces objectifs. Le Myanmar, le Sri Lanka et la Thaïlande ont signalé une diminution de 90% ou plus dans l'incidence ou la prévalence de la syphilis et/ou de la gonorrhée entre 1975 et 2005. Les données semblent indiquer une tendance à la baisse plus récente et moins significative des infections sexuellement transmissibles en Inde, entraînant une décrue régionale. Dans d'autres pays, soit le nombre d'infections sexuellement transmissibles demeure élevé ou continue sa progression, soit les informations disponibles ne sont pas suffisamment fiables pour en mesurer l'évolution. Le Sri Lanka et la Thaïlande ont établi de solides programmes de lutte contre les infections sexuellement transmissibles, permettant d'accéder à des services spécialement conçus pour leur prise en charge et prévoyant une intervention ciblée au sein des populations clés. De leur côté, l'Inde et le Myanmar ont déployé des efforts à grande échelle afin de mener des actions ciblées. D'autres pays de la région ont privilégié la lutte contre le virus de l'immunodéficience humaine; pour les autres infections sexuellement transmissibles, leurs ressources sont limitées. Aux niveaux national et infranational, les données révèlent un rapide déclin des infections sexuellement transmissibles lorsque la promotion ciblée pour encourager l'usage du préservatif et les services dédiés à la prise en charge de telles affections sont renforcés afin de toucher un plus grand nombre de travailleurs du sexe. En revanche, les épidémies d'infections sexuellement transmissibles observées dernièrement au sein de populations défavorisées d'hommes ayant des relations sexuelles avec d'autres hommes ont entraîné une hausse dans la région. Il est donc indispensable d'apporter une réponse remaniée et ciblée face aux infections sexuellement transmissibles dans la région en vue d'atteindre les objectifs mondiaux d'élimination.

La Organización Mundial de la Salud (OMS) fijó como objetivo una reducción del 90% en la incidencia de la sífilis y la gonorrea entre 2018 y 2030. Revisamos las tendencias de las infecciones de transmisión sexual en la Región del Sudeste Asiático de la OMS para evaluar la viabilidad de alcanzar estos objetivos. Myanmar, Sri Lanka y Tailandia informaron de reducciones del 90% o más en la incidencia o prevalencia de sífilis y/o gonorrea entre 1975 y 2005. Los datos sugieren que las reducciones más pequeñas y recientes en las tendencias de las infecciones de transmisión sexual en la India han impulsado los descensos regionales. En otros países, las infecciones de transmisión sexual siguen siendo elevadas o están aumentando, o los datos no son lo suficientemente fiables como para medir el cambio. Sri Lanka y Tailandia tienen sólidos programas de control de las infecciones de transmisión sexual que garantizan el acceso universal a los servicios para estas infecciones e intervenciones específicas en poblaciones clave. India y Myanmar han implementado esfuerzos de control específicos a gran escala. Otros países de la región han dado prioridad a la lucha contra el virus de la inmunodeficiencia humana y disponen de recursos limitados para otras infecciones de transmisión sexual. A nivel nacional y subnacional, los datos muestran un rápido descenso de las infecciones de transmisión sexual cuando se amplía la promoción del uso del preservativo y los servicios para las infecciones de transmisión sexual para llegar a un gran número de profesionales del ámbito sexual. Por el contrario, los recientes brotes de infecciones de transmisión sexual en poblaciones desatendidas de hombres que tienen relaciones sexuales con otros hombres se han relacionado con las tendencias al alza de las infecciones de transmisión sexual en la región. Se necesita una respuesta renovada y centrada en las infecciones de transmisión sexual en la región para alcanzar los objetivos mundiales de eliminación.

Incidence of tuberculosis in HIV-infected adults on first- and second-line antiretroviral therapy in India.

BACKGROUND: Programmatic data on the baseline risk of tuberculosis in people living with HIV (PLHIV) are needed to evaluate long-term effectiveness of the ongoing isoniazid preventive therapy (IPT) roll-out in India. METHODS: We estimated the incidence rate and risk factors of tuberculosis disease in adult PLHIV initiating first- and second-line anti-retroviral therapy (ART) prior to widespread IPT in a public ART center in Pune, India. RESULTS: 4067 participants contributing 5205.7 person-years of follow-up on first-line ART and 871 participants contributing 1031.7 person-years of follow-up on second-line ART were included in the analysis. The incidence rate of tuberculosis was 4.39 cases (95%CI 3.86-5.00) per 100 person-years on first-line ART and 1.64 cases (95%CI 1.01-2.63) per 100 person-years on second-line ART (p < 0.001). After adjusting for competing risks, male sex (aSHR = 1.33, 95%CI 1.02-1.74, p = 0.03), urban residence (aSHR = 1.53, 95%CI 1.13-2.07, p = 0.006) and CD4+ counts < 350 cells/mm3 (aSHR = 3.06 vs CD4 > 350 cells/mm3, 95%CI 1.58-5.94, p < 0.001) at ART initiation were associated with higher risk of tuberculosis independent of ART regimen. CONCLUSION: Risk of tuberculosis was lower in PLHIV receiving second-line ART compared to first-line ART. Prioritizing IPT in PLHIV with low CD4+ counts, urban residence and in males may further mitigate the risk of tuberculosis during ART.

Survival outcomes for first-line antiretroviral therapy in India's ART program.

BACKGROUND: Little is known about survival outcomes of HIV patients on first-line antiretroviral therapy (ART) on a large-scale in India, or facility level factors that influence patient survival to guide further improvements in the ART program in India. We examined factors at the facility level in addition to patient factors that influence survival of adult HIV patients on ART in the publicly-funded ART program in a high- and a low-HIV prevalence state. METHODS: Retrospective chart review in public sector ART facilities in the combined states of Andhra Pradesh and Telangana (APT) before these were split in 2014 and in Rajasthan (RAJ), the high- and a low-HIV prevalence states, respectively. Records of adults initiating ART between 2007-12 and 2008-13 in APT and RAJ, respectively, were reviewed and facility-level information collected at all ART centres and a sample of link ART centres. Survival probability was estimated using Kaplan-Meier method, and determinants of mortality explored with facility and patient-level factors using Cox proportional hazard model. RESULTS: Based on data from 6581 patients, the survival probability of ART at 60 months was 76.3 % (95 % CI 73.0-79.2) in APT and 78.3 % (74.4-81.7) in RAJ. The facilities with cumulative ART patient load above the state average had lower mortality in APT (Hazard ratio [HR] 0.74, 0.57-0.95) but higher in RAJ (HR 1.37, 1.01-1.87). Facilities with higher proportion of lost to follow-up patients in APT had higher mortality (HR 1.47, 1.06-2.05), as did those with higher ART to pre-ART patient ratio in RAJ (HR 1.62, 1.14-2.29). In both states, there was higher hazard for mortality in patients with CD4 count 100 cells/mm3 or less at ART initiation, males, and in patients with TB co-infection. CONCLUSIONS: These data from the majority of facilities in a high- and a low-HIV burden state of India over 5 years reveal reasonable and similar survival outcomes in the two states. The facilities with higher ART load in the longer established ART program in APT had better survival, but facilities with a higher ART load and a higher ratio of ART to pre-ART patients in the less experienced ART program in RAJ had poorer survival. These findings have important implications for India's ART program planning as it expands further.

Use of first line antiretroviral therapy from a free ART programme clinic in Pune, India - a preliminary report.

BACKGROUND & OBJECTIVES: The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India. METHODS: Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients. results: One hundred and forty two patients with median CD4 count of 109 cells/µl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/µl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8). INTERPRETATION & CONCLUSIONS: The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.

Integration of healthcare programs: a long-term policy perspective for a sustainable HIV program for India.

With the Government of India's initiative to ensure Universal Access to health through its flagship program of National Rural Health Mission, the debate on the economic efficiency and sustainability of a 'stand-alone' over 'integrated' programs has become extremely relevant. This study was conducted with the aim to establish opinion on the issue of sustainability of 'stand-alone' HIV program in India. Experts working on health policy development and implementation at various were interviewed on this issue and majority of experts interviewed were of the opinion that a 'stand-alone' HIV program is not sustainable in the long run because of inefficient use of resources. Integration of HIV program with the general health system is essential but it needs extensive planning. Areas like HIV testing centers, prevention of parent to child transmission and sexually transmitted infection diagnosis and treatment can be integrated with the general health system immediately.

Dried blood spot HIV-1 RNA quantification: a useful tool for viral load monitoring among HIV-infected individuals in India.

BACKGROUND & OBJECTIVES: Monitoring of HIV-infected individuals on antiretroviral treatment (ART) ideally requires periodic viral load measurements to ascertain adequate response to treatment. While plasma viral load monitoring is widely available in high-income settings, it is rarely used in resource-limited regions because of high cost and need for sophisticated sample transport. Dried blood spot (DBS) as source specimens for viral load measurement has shown promise as an alternative to plasma specimens and is likely to be a useful tool for Indian settings. The present study was undertaken to investigate the performance of DBS in HIV-1 RNA quantification against the standard plasma viral load assay. METHODS: Between April-June 2011, 130 samples were collected from HIV-1-infected (n=125) and non-infected (n=5) individuals in two district clinics in southern India. HIV-1 RNA quantification was performed from DBS and plasma using Abbott m2000rt system after manual RNA extraction. Statistical analysis included correlation, regression and Bland-Altman analysis. RESULTS: The sensitivity of DBS viral load was 97 per cent with viral loads >3.0 log 10 copies/ml. Measurable viral load (>3.0 log 10 copies/ml) results obtained for the 74 paired plasma-DBS samples showed positive correlation between both the assays (r=0.96). For clinically acceptable viral load threshold values of >5,000 copies/ml, Bland-Altman plots showed acceptable limits of agreement (-0.21 to +0.8 log 10 copies/ml). The mean difference was 0.29 log 10 copies/ml. The cost of DBS was $2.67 lower compared to conventional plasma viral load measurement in the setting. INTERPRETATION & CONCLUSIONS: The significant positive correlation with standard plasma-based assay and lower cost of DBS viral load monitoring suggest that DBS sampling can be a feasible and economical means of viral load monitoring in HIV-infected individual in India and in other resource-limited settings globally.

Prevalence of Hepatitis B and C Among Prison Inmates in India: A Systematic Review and Meta-Analysis.

Viral hepatitis is still considered a major cause of the burden of disease in India. It is the most common cause of cirrhosis and liver cancer. Prisoners are one of the groups at most risk for hepatitis. This study aimed to estimate the pooled estimates of the prevalence of hepatitis B and C among prisoners in India. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for study selection. The extensive search was done through databases of PubMed, Embase, and Google Scholar. All cross-sectional studies conducted to find the prevalence of hepatitis B and C among prison inmates in India published till June 2020 were screened and included in this meta-analysis. The analysis was conducted using the random-effects model. The heterogeneity was estimated using the I2 indicator. After extracting the required data, the meta-analysis was performed using the software Stata, version 12 (StataCorp LLC, College Station, Texas). The study is registered in the International Prospective Register of Systematic Reviews (PROSPERO; registration no: CRD42020185137). Out of a total of 970 articles searched through the database of PubMed, Embase, and Google Scholar, five studies that met the inclusion criteria were included and analyzed. Hepatitis B and C prevalence were given in four studies each. The results showed that the overall prevalence of hepatitis B and C in prisoners was 8% (95% CI: 4-12) and 7% (95% CI: 1-13). The studies show high heterogeneity with no evidence of publication bias. The prevalence of hepatitis B and C among male prisoners was 4.48% (95% CI: 3.64%-5.32%) and 6.35% (95% CI: 5.48%-7.23%), respectively, while the prevalence among female prisoners was 1.53% (95% CI: 0.31-2.75) and 2.10% (95% CI: 0.28-3.93), respectively. The study findings show a high prevalence of hepatitis B and C in prisoners, which is of particular concern. Appropriate and effective interventions to reduce the transmission of hepatitis B and C in prisons are essential.

Adoption of guidelines on and use of oral pre-exposure prophylaxis: a global summary and forecasting study.

BACKGROUND: In 2016, the UN General Assembly set a global target of 3 million oral pre-exposure prophylaxis (PrEP) users by 2020. With this target at an end, we aimed to assess global trends in the adoption of WHO PrEP recommendations into national guidelines and numbers of PrEP users, defined as people who received oral PrEP at least once in a given year, and to estimate future trajectories of PrEP use. METHODS: In this global summary and forecasting study, data on adoption of WHO PrEP recommendations and numbers of PrEP users were obtained through the Global AIDS Monitoring system and WHO regional offices. Trends in these indicators for 2016-19 by region and for 2019 by country were described, including by gender and priority populations where data were available. PrEP user numbers were forecasted until 2023 by selecting countries with at least 3 years of PrEP user data as example countries in each region to represent possible future PrEP user trajectories. PrEP user growth rates observed in example countries were applied to countries in corresponding regions under different scenarios, including a COVID-19 disruption scenario with static global PrEP use in 2020. FINDINGS: By the end of 2019, 120 (67%) of 180 countries with data had adopted the WHO PrEP recommendations into national guidelines (23 in 2019 and 30 in 2018). In 2019, there were about 626 000 PrEP users across 77 countries, including 260 000 (41·6%) in the region of the Americas and 213 000 (34·0%) in the African region; this is a 69% increase from about 370 000 PrEP users across 66 countries in 2018. Without COVID-19 disruptions, 0·9-1·1 million global PrEP users were projected by the end of 2020 and 2·4-5·3 million are projected by the end of 2023. If COVID-19 disruptions resulted in no PrEP user growth in 2020, the projected number of PrEP users in 2023 is 2·1-3·0 million. INTERPRETATION: Widespread adoption of WHO PrEP recommendations coincided with a global increase in PrEP use. Although the 2020 global PrEP target will be missed, strong future growth in PrEP use is possible. New PrEP products could expand the PrEP user base, and, with greater expansion of oral PrEP, further adoption of WHO PrEP recommendations, and simplified delivery, PrEP could contribute to ending AIDS by 2030. FUNDING: Unitaid, Bill & Melinda Gates Foundation, and WHO.

Two-year treatment outcomes of patients enrolled in India's national first-line antiretroviral therapy programme.

BACKGROUND: We aimed to analyse treatment outcomes of patients receiving first-line antiretroviral therapy (ART) through the national AIDS control programme of India. METHODS: Using routinely collected programme data, we analysed mortality, CD4 evolution and adherence outcomes over a 2-year period in 972 patients who received first-line ART between 1 October 2004 and 31 January 2005 at 3 government ART centres. Cox regression analysis was used to identify independent predictors of mortality. RESULTS: Of the 972 patients (median age 35 years, 66% men), 71% received the stavudinellamivudine/nevirapine regimen. The median CD4 count of enrolled patients was 119 cells/cmm (interquartile range [IQR] 50-200 cells/ cmm) at treatment initiation; 44% had baseline CD4 count <100 cells/cmm. Of the 927 patients for whom treatment outcomes were available, 71% were alive after 2 years of treatment. The median increase in CD4 count was 1 42 cells/ cmm (IQR 57-750 cells/cmm; n=616) at 6 months and 184 cells/cmm (IQR 102-299 cells/cmm; n=582) at 12 months after treatment. Over 2 years, 124 patients (13%) died; the majority of deaths (68%) occurred within the first 6 months of treatment. Those with baseline CD4 count <50 cells/cmm were significantly more likely to die (adjusted hazard ratio 2.5, 95% confidence interval 1.3-3.2) compared with patients who had baseline CD4 count >50 cells/cmm. Over the 2-year period, 323 patients (35%) missed picking up their monthly drugs at least once and 147 patients (16%) were lost to follow up. CONCLUSION: Survival rates of HIV-infected patients on first-line ART in India were comparable with those from other resource-limited countries. Most deaths occurred early and among patients who had advanced disease. Earlier initiation of HIV treatment and improving long term treatment adherence are key priorities for India's ART programme.

Markers of subclinical atherosclerotic disease in HIV-infected individuals.

BACKGROUND: Wider access to antiretroviral treatment (ART) has resulted in a decline in the number of people dying due to AIDS-related causes. However, with this increased longevity, accelerated rates of cardiovascular and atherosclerotic diseases are on the rise. We hypothesised that the prevalence of atherosclerotic cardiovascular diseases is greater in HIV/AIDS patients as compared to the normal population. Thus, we aimed to study the predictors of subclinical atherosclerotic disease in HIV-infected individuals. METHODS: In total, 168 HIV-positive individuals below 45 years of age (124 [73.08%] on ART and 44 [26.2%] ART naive) along with 150 age- and sex-matched healthy controls were recruited for this cross-sectional observational study. Carotid intimal medial thickness (cIMT), a surrogate marker of atherosclerosis, was assessed by a carotid colour doppler ultrasound and a mean of four measurements (both sides) were taken. cIMT was correlated with the age of the individuals, duration and type of ART, duration of disease and the level of immunodeficiency (CD4 cell count) along with conventional cardiac risk markers. RESULTS: In 168 HIV-positive individuals, the mean CD4 cell count was 332.41 ±17.1 cells/mm3. The mean cIMT of all HIV-positive individuals was 0.712 ±0.039 mm (0.596-0.840 mm) as compared to 0.616 ±0.023 mm (0.540-0.655 mm) in HIV-negative individuals (P<0.001). cIMT in HIV-positive individuals on ART (subgroup A) was 0.723 ±0.034 mm as compared to 0.682 ±0.038 mm in HIV-positive individuals not on ART (subgroup B) (P<0.01). Low CD4 cell counts, longer duration of HIV infection, exposure to ART and longer duration of ART were found to be independent predictors of a higher cIMT in HIV-positive subjects whereas age, diastolic blood pressure, low HDL, smoking and high BMI were predictors of high cIMT in HIV-negative controls. No difference was observed in cIMT among patients on different ART regimens but individuals who were on nevirapine had higher cIMT as compared to those who were on efavirenz, both non-nucleoside reverse transcriptase inhibitors (NNRTIs). CONCLUSIONS: Individuals with HIV infection (whether on ART or ART naive) have higher cIMT, and therefore a higher atherosclerotic burden, as compared to HIV-negative individuals. HIV infection itself, along with ART, overshadows conventional cardiac risk markers as a predictor of atherosclerotic disease in these individuals.

Decreasing cost of public sector first-line ART services in India from 2007-2008 to 2015-2016.

INTRODUCTION: India has scaled-up antiretroviral treatment (ART) in public sector facilities, but data to understand time trends of average cost of ART are limited. MATERIALS AND METHODS: Cost and output data were collected at all public sector ART centres in undivided Andhra Pradesh (high-HIV burden state) and Rajasthan (low-HIV burden state) in India from fiscal year 2007-2008 to 2012-2013. Average cost per patient for first-line ART, and its relation with scale of services, were assessed. Using data on scale of services, the average cost was estimated up to 2015-2016. Break-even point was estimated from average and marginal cost functions. Costs were adjusted to 2015 constant price. RESULTS: The average cost per patient alive and on ART in 2015-2016 was US$162 in undivided Andhra Pradesh and US$186 in Rajasthan, which was 51.4% and 35.8% lower than in 2007-2008, respectively. Average ART drug cost declined by 27.2% during this period, and was 70.9% and 61.5% of the total ART cost in the two states in 2015-2016. The average cost other than ART drugs declined by 73.1% and 45.7%, with the number of patients served increasing 7 and 14.2 times, respectively. Average cost other than ART drugs had a significant negative relation with scale (R2 = 86.4%-82.8%, p<0.001). Break-even analysis suggested that 47.5% and 58.8% of the ART centres in undivided Andhra Pradesh and Rajasthan, respectively, were functioning below optimal scale in 2015-2016. The estimated total economic cost of first-line ART services provided in the public sector in India in fiscal year 2015-2016 was US$ 151 million; it would be US$ 216.1 million to provide this to all eligible persons in India. CONCLUSION: The average cost of providing first-line ART has declined in India, and further reduction is possible if the optimal scale of services is achieved. These findings can inform resource requirement for the ART programme in India.

The cost-effectiveness and budgetary impact of a dolutegravir-based regimen as first-line treatment of HIV infection in India.

INTRODUCTION: Dolutegravir (DTG)-based antiretroviral therapy (ART) is recommended for first-line HIV treatment in the US and Europe. Efavirenz (EFV)-based regimens remain the standard of care (SOC) in India. We examined the clinical and economic impact of DTG-based first-line ART in the setting of India's recent guidelines change to treating all patients with HIV infection regardless of CD4 count. METHODS: We used a microsimulation of HIV disease, the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model, to project outcomes in ART-naive patients under two strategies: (1) SOC: EFV/tenofovir disoproxil fumarate (TDF)/lamivudine (3TC); and (2) DTG: DTG + TDF/3TC. Regimen-specific inputs, including virologic suppression at 48 weeks (SOC: 82% vs. DTG: 90%) and annual costs ($98 vs. $102), were informed by clinical trial data and other sources and varied widely in sensitivity analysis. We compared incremental cost-effectiveness ratios (ICERs), measured in $/year of life saved (YLS), to India's per capita gross domestic product ($1600 in 2015). We compared the budget impact and HIV transmission effects of the two strategies for the estimated 444,000 and 916,000 patients likely to initiate ART in India over the next 2 and 5 years. RESULTS: Compared to SOC, DTG improved 5-year survival from 76.7% to 83.0%, increased life expectancy from 22.0 to 24.8 years (14.0 to 15.5 years, discounted), averted 13,000 transmitted HIV infections over 5 years, increased discounted lifetime care costs from $3040 to $3240, and resulted in a lifetime ICER of $130/YLS, less than 10% of India's per capita GDP in 2015. DTG maintained an ICER below 50% of India's per capita GDP as long as the annual three-drug regimen cost was ≤$180/year. Over a 2- or 5-year horizon, total undiscounted outlays for HIV-related care were virtually the same for both strategies. CONCLUSIONS: A generic DTG-based regimen is likely to be cost-effective and should be recommended for initial therapy of HIV infection in India.

Antiretroviral resistance following immunological monitoring in a resource-limited setting of western India: A cross-sectional study.

BACKGROUND: The free antiretroviral therapy (ART) program in India still relies on the clinico-immunological monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following immunological monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. METHODS AND FINDINGS: This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60-153.50) cells/µL and 4.62 (IQR: 3.17-6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001). CONCLUSION: The option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by immunological monitoring due to accumulation of mutations. Introduction of routine PVL monitoring is a priority for the long-term sustainability of free ART program in India.

TB-HIV co-infection among pregnant women in Karnataka, South India: A case series.

Tuberculosis (TB) is a significant contributor to mortality in HIV-infected patients. Concurrent TB infection is also a significant contributing factor to maternal mortality in human immunodeficiency virus (HIV)-infected pregnant women. Studies addressing the outcomes of TB and HIV co-infection among pregnant women are generally infrequent. Although limited, the records maintained by the Revised National Tuberculosis Control Programme (RNTCP) and the National AIDS Control Programme (NACP) in Karnataka State, Southern India provide information about the numbers of pregnant women who are co-infected with TB and HIV and their pregnancy outcomes. We reviewed the data and conducted this study to understand how TB-HIV co-infection influences the outcomes of pregnancy in this setting. We sought to determine the incidence and treatment and delivery outcomes of TB-HIV co-infected pregnant women in programmatic settings in Karnataka State in southern India. The study participants were all the HIV-infected pregnant women who were screened for tuberculosis under the NACP from 2008 to 2012. For the purposes of this study, the program staff in the field gathered the data regarding on treatment and delivery outcomes of pregnant women. A total of seventeen pregnant women with TB-HIV co-infection were identified among 3,165,729 pregnant women (for an incidence of 5.4 per million pregnancies). The median age of these pregnant women was 24 years, and majority were primiparous women with WHO HIV stage III disease and were on a stavudine-based ART regimen. The maternal mortality rates were 18% before delivery and 24% after delivery. The abortion rate was 24%, and the neonatal mortality rate was 10%. The anti-tuberculosis treatment and anti-retroviral treatment outcome mortality rates were 30% and 53%, respectively. Although the incidence of TB among the HIV-infected pregnant women was marginally less than that among the non-HIV-infected women, the delivery outcomes were relatively poorer. The current strategy for the management of TB among the HIV-positive pregnant women needs urgent review.

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.

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.

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.

Feasibility of implementing an integrated tool for improvement of treatment quality and early-warning indicators for HIV drug resistance: a pilot study of centres in India.

With the rapid scale-up in use of antiretroviral therapy (ART), monitoring the quality of care and factors that may lead to emergence of HIV drug resistance (HIVDR) is an important focus point for programme managers. The National AIDS Control Organisation of India embarked on strengthening the ART programme for continuous quality improvement (CQI), using defined quality-of-care indicators (QCIs), including World Health Organization (WHO) early-warning indicators (EWIs) for HIVDR. In this feasibility study, done during July 2014, an integrated QCI and EWI tool developed by WHO India was pilot tested across 18 purposively selected ART centres. At seven ART centres, the EWI 1 target of >90% on-time pill pick-up was achieved for adult patients, while among the paediatric age group (<15 years old) it was not achieved by any centre. EWI 2 (retention of patients in ART care at 12 months after initiation) showed that two centres had retention of both adult and paediatric patients of >85% at 12 months of ART, while 11 centres had retention between 75% and 85%. EWI 3 (pharmacy stock-out) for adult and paediatric patients showed that 11 ART centres reported a minimum of one stock-out for the first-line ART drugs in the reporting period, while EWI 4 targets (pharmacy dispensing practices) were achieved by all the centres, for both adults and children. Average retention in care at 6, 12 and 24 months after ART initiation was 82%, 77% and 71%, respectively. This feasibility study showed that EWI analyses were much simpler to conduct if information was sought only for patients receiving ART, for whom the quality of record-keeping is better and more consistent. The activity has highlighted the need for improved quality of record-keeping at the facilities and implementation of specific interventions to ensure better patient follow-up. After modifications, use of the tool will be phased in across all the ART centres in India.

Retention of antiretroviral naïve patients registered in HIV care in a program clinic in Pune, India.

BACKGROUND: Retention in HIV care ensures delivery of services like secondary prevention, timely initiation of treatment, support, and care on a regular basis. The data on retention in pre antiretroviral therapy (ART) care in India is scanty. MATERIALS AND METHODS: Antiretroviral naïve HIV-infected adult patients registered between January 2011 and March 2012 in HIV care (pre-ART) were included in the study. The follow-up procedures were done as per the national guidelines. Patients who did not report to the clinic for 1 year were considered as pre-ART lost to follow-up (pre-ART LFU). They were contacted either telephonically or by home visits. Logistic regression analysis was done to find out factors associated with pre-ART loss to follow-up. RESULTS: A total of 689 antiretroviral naïve adult patients were registered in the HIV care. Fourteen (2%) patients died and 76 (11%) were LFU till March 2013. The multivariate analysis showed that baseline CD4 count >350 cells/mm(3) (P < 0.01) and illiteracy (P = 0.044) were significantly associated with LFU. Of the total pre-ART LFUs, 35 (46.1%) informed that they would visit the clinic at their convenient time. NGOs that referred 16 female sex workers (FSWs) who were LFU (21.1%) informed that they would make efforts to refer them to the clinic. CONCLUSION: Higher CD4 count and illiteracy were significantly associated with lower retention in pre-ART care. Developing effective "retention package" for patients and strengthening linkage strategies between key sub-population such as FSWs and ART programming will help to plug the leaky cascade in HIV care.