AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

BACKGROUND: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent. METHODS: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. RESULTS: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. CONCLUSIONS: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r).

Progress towards achieving viral hepatitis B and C elimination in the Asia and Pacific region: Results from modelling and global reporting.

In 2016, Asia and Pacific countries endorsed action plans for reaching viral hepatitis elimination targets set in the Global Health Sector Strategy (GHSS) for Viral Hepatitis 2016-2021. We examine the region's progress by modelling disease burden and constructing the cascade of care. Between 2015 and 2020, chronic HBV prevalence declined from 4.69% to 4.30%, and HCV prevalence declined from 0.64% to 0.58%. The region achieved the 2020 target of 30% incidence reduction for HBV, whereas HCV incidence declined by 6%. Hepatocellular carcinoma incidence for HBV and HCV increased by 9% and 7%, respectively. Liver-related deaths from HBV rose by 8%, and mortality attributable to HCV plateaued. Large testing and treatment gaps remained in 2019: only 13% of chronic HBV infections were diagnosed and 25% treated; 21% of chronic HCV infection were diagnosed and 11% treated. Viral hepatitis must become national priority with adequate funding to reach elimination goals by 2030.

Seroprevalence and burden of hepatitis C virus infection in WHO South-East Asia Region: A systematic review.

BACKGROUND: This systematic review was aimed to estimate hepatitis C virus (HCV) seroprevalence and burden in disease in WHO South East Asia Region (SEAR). METHODS: Electronic databases (PubMed, Scopus, Embase, and Google Scholar) and websites of non-indexed national medical journals, government and international health agencies were searched to identify English language literature published between 1991 and June 2020. We selected the studies reporting HCV seroprevalence in asymptomatic general (low-risk) and high-risk adult populations, that is, persons living with HIV (PLHIV), persons who inject drugs (PWID), sex workers, persons on maintenance hemodialysis (MHD), people in prison, and men sex with men (MSM). Seroprevalence data were combined to estimate weighted pooled prevalence (95% confidence interval) in each group and in each country, using the random-effects model. Estimated pooled seroprevalences were multiplied with estimated populations at risk to estimate the overall HCV burden. RESULTS: The analysis included 538 studies (35 Bangladesh, 6 Bhutan, 2 DPR Korea, 323 India, 43 Indonesia, 2 Maldives, 18 Myanmar, 29 Nepal, 11 Sri Lanka, 67 Thailand, and 2 Timor-Leste). In SEAR, the weighted pooled anti-HCV seroprevalence was estimated as 0.84% (0.56-1.12) in low-risk population and 13.67% (10.95-16.40) in PLHIV, 51.44% (43.67-59.20) in PWID, 25.80% (20.34-32.09) in MHD, 8.39% (5.84-11.51) in prison inmates, 2.69% (1.43-4.13) in people with high-risk sex behavior, and 11.43% (8.61-14.74) in MSM. The total HCV burden in low-risk and high-risk populations in SEAR countries was estimated as 12.45 million and 1.65 million, respectively. CONCLUSION: Our estimates of HCV seroprevalence and burden should help the respective countries in planning their HCV elimination strategies.

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.

Perspectives on voluntary assisted partner notification among providers, people with HIV and the general population in Indonesia: a formative qualitative study.

BACKGROUND: Voluntary assisted partner notification (aPN) services are effective in increasing access to and uptake of HIV testing among partners of people with HIV. Following recommendations by the World Health Organization in 2016, Indonesia evaluated various approaches to aPN. We present the lessons learned from formative operational research undertaken to understand provider and patient perspectives on aPN from three demonstration sites in cities with a high HIV burden. METHODS: We conducted a formative qualitative study in three cities: Jakarta, Semarang, and Denpasar between September and October 2019. We conducted six focus group discussions (FGDs) (n = 44 participants) among health-care providers, people living with HIV and the general population. We explored participant preferences and concerns about how aPN should be delivered, including the methods of and messaging for contacting partners. All FGDs were conducted in the Indonesian language. Qualitative data were analysed using thematic analysis. RESULTS: aPN was acceptable across different participant populations, although with caveats. Some differences were observed between the general population, providers and people living with HIV. People living with HIV were mainly concerned with confidentiality of the procedure and preferred the use of telecommunication and messages that avoid explicit mention of HIV exposure. Providers preferred similar approaches but for different reasons, being concerned mainly with self-efficacy and security. There was consensus regarding dual referral models. The use of phone calls and short messages were preferred as these are perceived to minimize negative reactions and stigma, protect client confidentiality and are suitable in the current legal situation. The general population was mainly concerned with effectiveness and prefer direct provider-led approaches, such as preferring in-person meeting with explicit notification of potential HIV exposure. CONCLUSIONS: We found consensus among stakeholders on acceptance of aPN, especially dual referral methods. Development and implementation of aPN protocols should also consider clients' individual situations and concerns regarding safeguarding of confidentiality, and offer a range of options to accommodate all stakeholders involved.

A rapid review of pre-exposure prophylaxis for HIV in the Asia-Pacific region: recommendations for scale up and future directions.

Decline in new HIV infections in the Asia-Pacific region (APAC) continues to be slow, emphasising the importance of scaling up new HIV prevention strategies, such as pre-exposure prophylaxis (PrEP). To help inform PrEP rollout in APAC, we conducted a rapid review of published literature on PubMed from 2015 to 2020, to assess feasibility, implementation strategies, cost-effectiveness, and availability of national policies and guidelines; for the latter, we also did an expanded Internet search. This review focussed on nine countries contributing >95% of new infections in this region. A total of 36 PrEP-related studies conducted among men who have sex with men, female sex workers, and transgender women were included, of which 29 were quantitative, six were qualitative and one was a mixed-method study. Most of the studies have addressed the availability and acceptability of PrEP, whereas cost-effectiveness of any approach was assessed by limited studies. Limited published information was available about national PrEP policies and guidelines; of the selected nine countries, five have adopted the recommended World Health Organization PrEP policy of which four have integrated it in their national HIV response. HIV risk perception concerns about safety, side-effects, stigma, and affordability were major challenges to PrEP acceptance. Community-based implementation has the potential to address these. Limited evidence suggested merging PrEP implementation with ongoing targeted intervention and treatment programs could be a cost-effective approach. To stem the epidemic, newer effective prevention strategies, like PrEP, should be urgently adopted within the context of combination HIV prevention approaches.

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.

GeneXpert HIV-1 quant assay, a new tool for scale up of viral load monitoring in the success of ART programme in India.

BACKGROUND: Recent WHO guidelines identify virologic monitoring for diagnosing and confirming ART failure. In view of this, validation and scale up of point of care viral load technologies is essential in resource limited settings. METHODS: A systematic validation of the GeneXpert® HIV-1 Quant assay (a point-of-care technology) in view of scaling up HIV-1 viral load in India to monitor the success of national ART programme was carried out. Two hundred nineteen plasma specimens falling in nine viral load ranges (<40 to >5 L copies/ml) were tested by the Abbott m2000rt Real Time and GeneXpert HIV-1 Quant assays. Additionally, 20 seronegative; 16 stored specimens and 10 spiked controls were also tested. Statistical analysis was done using Stata/IC and sensitivity, specificity, PPV, NPV and %misclassification rates were calculated as per DHSs/AISs, WHO, NACO cut-offs for virological failure. RESULTS: The GeneXpert assay compared well with the Abbott assay with a higher sensitivity (97%), specificity (97-100%) and concordance (91.32%). The correlation between two assays (r = 0.886) was statistically significant (p < 0.01), the linear regression showed a moderate fit (R2 = 0.784) and differences were within limits of agreement. Reproducibility showed an average variation of 4.15 and 3.52% while Lower limit of detection (LLD) and Upper limit of detection (ULD) were 42 and 1,740,000 copies/ml respectively. The misclassification rates for three viral load cut offs were not statistically different (p = 0.736). All seronegative samples were negative and viral loads of the stored samples showed a good fit (R2 = 0.896 to 0.982). CONCLUSION: The viral load results of GeneXpert HIV-1 Quant assay compared well with Abbott HIV-1 m2000 Real Time PCR; suggesting its use as a Point of care assay for viral load estimation in resource limited settings. Its ease of performance and rapidity will aid in timely diagnosis of ART failures, integrated HIV-TB management and will facilitate the UNAIDS 90-90-90 target.

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.

Virological efficacy with first-line antiretroviral treatment in India: predictors of viral failure and evidence of viral resuppression.

OBJECTIVE: Combination antiretroviral therapy (ART) has improved in efficacy, durability and tolerability. Virological efficacy studies in India are limited. We determined incidence and predictors of virological failure among patients initiating first-line ART and described virological resuppression after confirmed failure, with the goal of informing national policy. METHODS: Therapy-naïve patients initiated on first-line ART as per national guidelines were monitored every 3 months for adherence and virological response over 2 years. Genotyping on baseline samples was performed to assess primary drug resistance. Multivariate Cox regression analysis was used to assess predictors of virological failure. RESULTS: Virological failure rate among 599 eligible patients was 10.7 failures per 100 person-years. Cumulative failure incidence was 13.2% in the first year and 16.5% over 2 years. Patients initiated on tenofovir had a significantly lower rate of virological failure than those on stavudine or zidovudine (6.7 vs. 11.9 failures per 100 person-years, P = 0.013). Virological failure was independently associated with age <40 years, mean adherence <95%, non-tenofovir-containing regimens and presence of primary drug resistance. In a subset of 311 patients who were reassessed after treatment failure, 19% (11/58) patients resuppressed their viral load to <400 copies/ml after confirmed virological failure. CONCLUSIONS: Our results support the inclusion of tenofovir as first-line ART in resource-limited settings and a role for regular adherence counselling and virological monitoring for enhanced treatment success. Detection of early virological failure should provide an opportunity to augment adherence counselling and repeat viral load testing before therapy switch is considered.

Nevirapine versus efavirenz-based antiretroviral therapy regimens in antiretroviral-naive patients with HIV and tuberculosis infections in India: a pilot study.

BACKGROUND: Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings. METHODS: A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART. RESULTS: Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14.1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p =0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group. CONCLUSIONS: Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection. TRIAL REGISTRATION: NCT No. 01805258.

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.

TB treatment outcomes among TB-HIV co-infections in Karnataka, India: how do these compare with non-HIV tuberculosis outcomes in the province?

BACKGROUND: India accounts for 23% of the global incidence of TB cases; it also has an estimated 2.3 million HIV infections. Of the 2 million TB incident cases, 5% occurred in HIV infected persons. The country has large national TB and HIV control programs. This paper describes characteristics of TB-HIV co-infection cases registered under the program in Karnataka province, India. Treatment outcomes for coinfected patients are compared with those for TB patients in the province. METHODS: Program reports from the National AIDS Control program and the National TB control program for Karnataka province (a high HIV prevalence state, population 61 million) were analysed. Data from patients registered in each program in 2010-2011 was studied. RESULTS: Of the 6,480 adult co-infections, a third occurred in women; 78% of patients were initiated on ART. Among the cohort 73% had pulmonary TB, and 46% reported sputum positivity for acid fast bacilli. Treatment success among co-infected patients not on ART (54%) were significantly lower compared to those already on ART (80%); death and default rates were higher in the non-ART group. Treatment success proportions (75%) for the co-infected patients were similar to those for the 51,966 patients registered under the TB program. Death rates among co-infected patients (15%) were twice as high as for TB patients under the program, though default and failure rates were lower. CONCLUSION: Co-infected patients already on ART demonstrated better TB outcomes in than those not on ART. Compared to those with TB only, co-infected patients had similar TB treatment success rates and lower rates of treatment default and failure. Integration of TB-HIV collaborative activities will strengthen our battle to control TB and HIV globally.

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.

Global reporting of progress towards elimination of hepatitis B and hepatitis C.

BACKGROUND: The 69th World Health Assembly endorsed the global health sector strategy on viral hepatitis to eliminate viral hepatitis as a public health threat by 2030. Achieving and measuring the 2030 targets requires a substantial increase in the capacity to test and treat viral hepatitis infections and a mechanism to monitor the progress of hepatitis elimination. This study aimed to identify the gaps in data availability or quality and create a new mechanism to monitor the progress of hepatitis elimination. METHODS: In 2020, using a questionnaire, we collected empirical, systematic, modelled, or surveyed data-reported by WHO country and WHO regional offices-on indicators of progress towards elimination of viral hepatitis, including burden of infection, incidence, mortality, and the cascade of care, and validated these data. FINDINGS: WHO received officially validated country-provided data from 130 countries or territories, and used partner-provided data for 70 countries or territories. We estimated that in 2019, globally, 295·9 million (3·8%) people were living with chronic hepatitis B virus (HBV) infection and 57·8 million (0·8%) people were living with chronic hepatitis C virus (HCV) infection. Globally, there were more than 3·0 million new infections with HBV and HCV and more than 1·1 million deaths due to the viruses in 2019. In 2019, 30·4 million (95% CI 24·3-38·0) individuals living with hepatitis B knew their infection status and 6·6 million (5·3-8·3) people diagnosed with hepatitis B received treatment. Among people with HCV infection, 15·2 million (95% CI 12·1-19·0) had been diagnosed between 2015 and 2019, and 9·4 million (7·5-11·7) people diagnosed with hepatitis C infection were treated with direct-acting antiviral drugs between 2015 and 2019. INTERPRETATION: There has been notable global progress towards hepatitis elimination. In 2019, 30·4 million (10·3%) people living with hepatitis B knew their infection status, which was slightly higher than in 2015 (22·0 million; 9·0%), and 6·6 million (22·7%) of those diagnosed with hepatitis B received treatment, compared with 1·7 million (8·0%) in 2015. Mortality from hepatitis C has declined since 2019, driven by an increase in HCV treatment ten times that of the strategy baseline. However, an estimated 89·7% of HBV infections and 78·6% of HCV infections remain undiagnosed. A new global strategy for 2022-30, based on these new estimates, should be implemented urgently to scale up the screening and treatment of viral hepatitis. FUNDING: World Health Organization.

Utility of the point of care CD4 analyzer, PIMA, to enumerate CD4 counts in the field settings in India.

BACKGROUND: In resource limited settings non-availability of CD4 count facility at the site could adversely affect the ART roll out programme. Point of care CD4 enumerating equipments can make the CD4 count available at the site of care and improve the patients' management considerably. This study is aimed at determining the utility of a Point of Care PIMA CD4 analyzer (Alere, Germany) in the field settings in India. METHOD: The blood samples were collected from 1790 participants at 21 ART centers from different parts of the country and tested using PIMA and the reference methods (FACSCalibur, FACSCount and CyFlow SL3). The paired finger prick and venous blood samples from 175 participants were tested by the PIMA CD4 Analyzer and then by FACSCalibur. RESULT: The CD4 counts obtained by PIMA CD4 analyzer showed excellent correlation with the counts obtained by the reference methods; for venous blood the Pearson's r was 0.921, p < 0.001 and the relative bias was 0.2% (range: -42 to 42%) and for finger prick samples, the Pearson's r was 0.856 and the relative bias was -9.1% (range: -46% to 27%). For CD4 ranges; <250, 251-350, 351-500 and >500 cells/mm3, the differences in the median CD4 counts obtained by the reference method and the PIMA analyzer were not significant (P > 0.05) and the relative bias were low (-7 to 5.1%). The Intermachine comparison showed variation within the acceptable limit of%CV of 10%. CONCLUSION: In the field settings, the POC PIMA CD4 analyzer gave CD4 counts comparable to the reference methods for all CD4 ranges. The POC equipment could identify the patients eligible for ART in 91% cases. Adequate training is necessary for finger prick sample collection for optimum results. Decentralization of CD4 testing by making the CD4 counts available at primary health centers, especially in remote areas with minimum or no infrastructure would reduce the missed visits and improve adherence of the patients.

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.

Assessment of country implementation of the WHO global health sector strategy on sexually transmitted infections (2016-2021).

BACKGROUND: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030. METHODS: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS. RESULTS: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries. CONCLUSIONS: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets.

HIV TB coinfection - perspectives from India.

Introduction: HIV and tuberculosis (TB) are two of the most challenging infections faced by humanity and place immense burden on health care systems worldwide. Both HIV and TB impact one another's progression.Areas covered: HIV is the most important risk factor for progression of latent TB to active disease. TB is the most common cause of death among People Living with HIV (PLHIV). Timely detection of TB among PLHIV and screening for HIV among TB patients, early initiation of ART and ATT among coinfected persons, provision of CPT and TB Preventive therapy along with control of air-borne infection are some of the key activities to reduce morbidity and mortality among coinfected persons. Despite many challenges, the collaboration between two programs has yielded good results and globally more than 7.3 million lives of PLHIV have been saved globally through scale-up of collaborative TB/HIV activities since 2005. The review looked into key features of both programs that are the collaboration strategies and challenges that still need to be addressed.Expert opinion: The overarching principle for effective implementation of collaborative activities is integration of the TB and HIV national programs right from policy making to service delivery and monitoring.

Assessing the Effectiveness of a Telemedicine Initiative in Clinical Management of Children Living with HIV/AIDS in Maharashtra, India.

AIMS: To evaluate the effectiveness of telemedicine in the clinical management of children living with HIV/AIDS in resource-limited settings ; Background: Telemedicine is an important mechanism for service delivery in health care settings, both in resource-rich and resource-poor settings. Such service delivery mechanisms have shown to be associated with virologic suppression and higher CD4 counts. These services are also associated with improved access, shorter visiting times, and higher patient satisfaction. ; Objective: We designed the present two-group comparison study to compare the clinical evaluation and management of children in the anti-retroviral therapy (ART) centres linked to telemedicine facility with those who are not linked to this facility in Maharashtra, India. ; Methods: We analysed clinical records from six ART centres in Maharashtra; of these, 250 children were in the linked ART centres and 301 were in the non-linked ART centres. The outcomes were classified according to investigations, management, and monitoring. For management, we evaluated: 1) Initiation of cotrimoxazole prophylaxis; 2) Children not initiated on ART when required; 3) ART regime after appropriate investigations; and 4) Change of regime (if immunologically indicated). For monitoring, we assessed the haematological monitoring of children on ART. ; Results: The mean (SD) ages of children in linked and non-linked ART centres were 10.8 (4.6) and 10.9 (4.6) years, respectively (p=0.80). After adjusting for individual and structural level variables, physical examination (OR: 2.0, 95% CI; 1.2, 3.2), screening for tuberculosis (OR: 12.9, 95% CI: 2.0, 82.9) and cotrimoxazole prophylaxis were significantly more likely in the linked centres compared with non-linked centres (OR: 1.8, 95% CI: 1.4, 2.2). A higher proportion of children eligible for ART were not initiated on treatment in the non-linked centres compared with linked centres (26% vs. 8%, p=0.06). Children were less likely to be initiated on zidovudine-based regimens without baseline haemoglobin or with baseline haemoglobin of less than 9 gm% in linked centres (OR: 0.7, 95% CI: 0.6, 0.8). Similarly, children in the linked centres were less likely to have been started on nevirapine-based regimens without baseline liver enzymes (OR: 0.8, 95% CI: 0.7, 0.9). ; Conclusion: Thus, the overall clinical management of Children Living with HIV/ AIDS (CLHA) was better in ART centres linked with the telemedicine initiative compared with those who were not linked. Children in the linked ART centres were more likely to have a complete baseline assessment (physical, hematological, radiological, and screening for TB); the presence of a pediatrician in the centres was helpful.