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.

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.

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.

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.

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.

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.

Community action for people with HIV and sex workers during the COVID-19 pandemic in India.

Sex workers have been one of the marginalized groups that have been particularly affected by India's stringent lockdown in response to the coronavirus disease 2019 (COVID-19) pandemic. The sudden loss of livelihood and lack of access to health care and social protection intensified the vulnerabilities of sex workers, especially those living with HIV. In response, Ashodaya Samithi, an organization of more than 6000 sex workers, launched an innovative programme of assistance in four districts in Karnataka. Since access to antiretroviral therapy (ART) was immediately disrupted, Ashodaya adapted its HIV outreach programme to form an alternative, community-led system of distributing ART at discreet, private sites. WhatsApp messaging was used to distribute information on accessing government social benefits made available in response to the COVID-19 pandemic. Other assistance included advisory messages posted in WhatsApp groups to raise awareness, dispel myths and mitigate violence, and regular, discreet phone check-ins to follow up on the well-being of members. The lessons learnt from these activities represent an important opportunity to consider more sustainable approaches to the health of marginalized populations that can enable community organizations to be better prepared to respond to other public health crises as they emerge.

Impact of COVID-19 on the global supply chain of antiretroviral drugs: a rapid survey of Indian manufacturers.

Most people living with HIV in low- and middle-income countries are treated with generic antiretroviral (ARV) drugs produced by manufacturers in India - the "pharmacy of the developing world". India's nationwide lockdown in March 2020 in response to the coronavirus disease 2019 (COVID-19) pandemic therefore prompted concerns about disruption to this essential supply. A preliminary assessment of ARV drug manufacturers in India in March 2020 indicated a range of concerns. This prompted a rapid questionnaire-based survey in May 2020 of eight manufacturers that account for most of India's ARV drug exports. The greatest challenges reported were in international shipping, including delays, increased lead times and rising costs. Contrary to expectations, lack of access to the active pharmaceutical ingredients (APIs) required for ARV drug manufacture was not a major hindrance, as manufacturers reported that their reliance on China for API supplies had reduced in recent years. However, their reliance on overseas markets for the raw materials required for local API synthesis was a major challenge. The findings from this survey have implications for addressing some of the immediate and medium-term concerns about the production and supply of generic ARV drugs. Long-term orders to support multi-month dispensing and buffer stocks need to be in place, together with computerized inventory management systems with real-time information from the lowest-level dispensation unit. Manufacturers and industry associations should have regular, formal interaction with the key ministries of the Government of India regarding these issues. Measures to improve the resilience of the generic ARV drug supply system are essential to minimize ongoing supply shocks resulting from the COVID-19 pandemic and to prepare for future emergencies.

Quality and effectiveness of counselling at antiretroviral therapy centres in India: capturing counsellor and beneficiary perspectives.

BACKGROUND: Ensuring the quality and effectiveness of counselling is imperative for enabling people living with HIV to cope with treatment adherence. Countrywide assessment of antiretroviral therapy (ART) centres was undertaken to assess the quality and effectiveness of counselling. The insights gained from the assessment are expected to build an improved understanding of the counselling aspect and contribute to informing decisions strengthening the counselling provided at ART centres. METHODS: Assessment of counselling at 357 ART centres entailed interviews with counsellors and beneficiaries using a structured questionnaire administered by trained technical experts. Two counsellors and five beneficiaries at each ART centre were interviewed to assess both the quality and effectiveness of counselling. Beneficiaries were selected from different risk groups to understand their varied concerns and experiences. RESULTS: During the assessment, 618 counsellors were interviewed (45% women); also, 1785 beneficiaries were interviewed, consisting of 892 (49.9%) men, 857 (48.1%) women and 36 (2.0%) transgender. Counsellors were found to be relatively well informed on topics pertaining to pre-ART, ART preparedness and positive healthy living, and the psychosocial support extended to patients. Counsellors surveyed were not aware of critical areas such as counselling of pregnant women (44.5%) , drug adherence (44.8%) and the use of information, education and communication material during counselling, and pill count. The majority of beneficiaries reported being informed on issues pertaining to retention; however, 30-40% of beneficiaries were not informed regarding the critical elements of adherence such as counselling on ART side effects (68.5%), pill count (62.8%) and information on access to social benefit schemes (25.7%). Factors such as client volume, the training of the counsellors and adequate space for counselling affected the quality of counselling. CONCLUSION: With concerted efforts in bridging the gaps in knowledge, infrastructure and information needs, India's national AIDS control programme (NACP) can enhance the counselling services at ART centres and improve the quality of services for patient retention.

Adoption of the 2015 World Health Organization guidelines on antiretroviral therapy: Programmatic implications for India.

The therapeutic and preventive benefits of early initiation of antiretroviral therapy (ART) for HIV are now well established. Reflecting new research evidence, in 2015 the World Health Organization (WHO) recommended initiation of ART for all people living with HIV (PLHIV), irrespective of their clinical staging and CD4 cell count. The National AIDS Control Programme (NACP) in India is currently following the 2010 WHO ART guidelines for adults and the 2013 guidelines for pregnant women and children. This desk study assessed the number of people living with HIV who will additionally be eligible for ART on adoption of the 2015 WHO recommendations on ART. Data routinely recorded for all PLHIV registered under the NACP up to 31 December 2015 were analysed. Of the 250 865 individuals recorded in pre-ART care, an estimated 135 593 would be eligible under the WHO 2013 guidelines. A further 100 221 would be eligible under the WHO 2015 guidelines. Initiating treatment for all PLHIV in pre-ART care would raise the number on ART from 0.92 million to 1.17 million. In addition, nearly 0.07 million newly registered PLHIV will become eligible every year if the WHO 2015 guidelines are adopted, of which 0.028 million would be attributable to implementation of the WHO 2013 guidelines alone. In addition to drugs, there will be a need for additional CD4 tests and tests of viral load, as the numbers on ART will increase significantly. The outlay should be seen in the context of potential health-care savings due to early initiation of ART, in terms of the effect on disease progression, complications, deaths and new infections. While desirable, adoption of the new guidance will have significant programmatic and resource implications for India. The programme needs to plan and strengthen the service-delivery mechanism, with emphasis on newer and innovative approaches before implementation of these guidelines.

Delivery of antiretroviral treatment services in India: Estimated costs incurred under the National AIDS Control Programme.

Competing domestic health priorities and shrinking financial support from external agencies necessitates that India's National AIDS Control Programme (NACP) brings in cost efficiencies to sustain the programme. In addition, current plans to expand the criteria for eligibility for antiretroviral therapy (ART) in India will have significant financial implications in the near future. ART centres in India provide comprehensive services to people living with HIV (PLHIV): those fulfilling national eligibility criteria and receiving ART and those on pre-ART care, i.e. not on ART. ART centres are financially supported (i) directly by the NACP; and (ii) indirectly by general health systems. This study was conducted to determine (i) the cost incurred per patient per year of pre-ART and ART services at ART centres; and (ii) the proportion of this cost incurred by the NACP and by general health systems. The study used national data from April 2013 to March 2014, on ART costs and non-ART costs (human resources, laboratory tests, training, prophylaxis and management of opportunistic infections, hospitalization, operational, and programme management). Data were extracted from procurement records and reports, statements of expenditure at national and state level, records and reports from ART centres, databases of the National AIDS Control Organisation, and reports on use of antiretroviral drugs. The analysis estimates the cost for ART services as US$ 133.89 (?8032) per patient per year, of which 66% (US$ 88.66, ?5320) is for antiretroviral drugs and 34% (US$ 45.23, ?2712) is for non-ART recurrent expenditure, while the cost for pre-ART care is US$ 33.05 (?1983) per patient per year. The low costs incurred for patients in ART and pre-ART care services can be attributed mainly to the low costs of generic drugs. However, further integration with general health systems may facilitate additional cost saving, such as in human resources.

Lamivudine-Induced Skin Rash Remains an Underdiagnosed Entity in HIV: A Case Series from a Single Center.

BACKGROUND: Hypersensitivity reaction to antiretroviral treatment (ART) poses potential threats in maintenance of treatment. Lamivudine (3TC), is rare to cause rash. We are reporting 23 cases of 3TC-induced rash. METHODS: An observational study conducted in the antiretroviral treatment center of a tertiary care hospital of North India from Feb 2009-Dec 2013 to record 3TC-induced rash. These were then recommended to start ART without 3TC and were followed up at 1-, 2-, and at 4-week intervals to monitor the toxicity, if any, with alternate therapy. RESULTS: We observed 3TC-induced skin rash in 23 HIV-infected individuals (0.7%), out of 3213 HIV-infected individuals initiated on first line ART (zidovudine [ZDV]/tenofovir [TDF] + 3TC +nevirapine [NVP]/efavirenz [EFV] during the study period of 5 years [Feb 2009-Dec 2013]). The mean age of these 23 individuals was 37.5 ± 12.8 (17-60) years. Lamivudine rash was more common in women than men (F = 19, M = 4), with an overall mean age of 37.5 ± 12.8 (17-60) years. It was generalized, erythematous, maculopapular eruptions associated with intense itching with no associated mucosal involvement. Lamivudine was substituted with TDF in 19, didanosine (ddl) in 3 and abacavir (ABC) in 1 individual. Mean duration of follow-up is 11.1 ± 12.8 (3-42) months. CD4 count was repeated at 3 months and showed significant improvement (P = 0.002). CONCLUSION: Lamivudine-induced rash was found at a frequency of 0.7%. The correct and early recognition that the rash is due to 3TC, would save unnecessary substitution to a different class of drugs.

Predictors and Timing of ATT Initiation among HIV-TB Patients at ART Centers of Karnataka, India: Two Year Follow-Up.

BACKGROUND: In India, TB and HIV co-infection remains as a serious public health problem. From 2006 onwards, the intensified TB-HIV collaborative activities are being jointly implemented by National AIDS Control Programme (NACP) and Revised National TB Control programme (RNTCP) at high HIV burden states. OBJECTIVES: To determine (a) the predictors of outcome among a cohort of HIV-TB co-infected patients after two years after initiation of ART treatment. (b) prognostic significance of time difference between the initiation of ATT and ART in HIV-TB co-infected patients. METHODS: Patients registered at sixteen ART centres in Karnataka, from October through December 2009 formed the study cohort and were followed till December 2011. RESULTS: A total of 604 HIV-TB patients were registered. Follow-up (a) at the end of one year had shown 63.6% (377)patients with unfavorable TB treatment outcomes (b) at the end of second year, 55.6% (336)patients were alive on ART treatment. The variables male, smear negative TB, CD4 count less than 50cells per cumm and unfavorable TB outcome were significantly associated with unfavorable ART treatment outcome. CONCLUSIONS: The programmes need to review the existing strategies and strengthen HIV-TB collaborative activities for timely treatment initiation with intensive monitoring of HIV-TB patients on treatment.

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.

MicroRNA-150 is a potential biomarker of HIV/AIDS disease progression and therapy.

BACKGROUND: The surrogate markers of HIV/AIDS progression include CD4 T cell count and plasma viral load. But, their reliability has been questioned in patients on anti-retroviral therapy (ART). Five microRNAs (miRNAs) - miR-16, miR-146b-5p, miR-150, miR-191 and miR-223 in peripheral blood mononuclear cells (PBMCs) were earlier found to assign HIV/AIDS patients into groups with varying CD4 T cell counts and viral loads. In this pilot study, we profiled the expression of these five miRNAs in PBMCs, and two of these miRNAs (miR-146b-5p and miR-150) in the plasma of HIV/AIDS patients, including those on ART and those who developed ART resistance, to evaluate if these are biomarkers of disease progression and therapy. RESULTS: We quantified miRNA levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RNA isolated from PBMCs and plasma of healthy persons or HIV-infected patients who were (1) asymptomatic; (2) symptomatic and ART naïve; (3) on ART; and (4) failing ART. Our results show miR-150 (p<0.01) and to a lesser extent miR-146b-5p (p<0.05) levels in PBMCs to reliably distinguish between ART-naïve AIDS patients, those on ART, and those developing drug resistance and failing ART. The plasma levels of these two miRNAs also varied significantly between patients in these groups and between patients and healthy controls (p values <0.05). CONCLUSIONS: We report for the first time that PBMC and plasma levels of miR-150 and miR-146b-5p are predictive of HIV/AIDS disease progression and therapy.

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.

Nuclear magnetic resonance based profiling of biofluids reveals metabolic dysregulation in HIV-infected persons and those on anti-retroviral therapy.

BACKGROUND: Although HIV causes immune deficiency by infection and depletion of immunocytes, metabolic alterations with clinical manifestations are also reported in HIV/AIDS patients. Here we aimed to profile metabolite changes in the plasma, urine, and saliva of HIV/AIDS patients, including those on anti-retroviral therapy (ART). METHODS: Metabolic profiling of biofluids collected from treatment naïve HIV/AIDS patients and those receiving ART was done with solution-state nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation. RESULTS: In Principal Component Analysis (PCA) of the NMR spectra, Principal Component 1 (PC1) alone accounted for 99.3%, 87.2% and 78.8% variations in plasma, urine, and saliva, respectively. Partial least squares discriminant analysis (PLS-DA) was applied to generate three-component models, which showed plasma and urine to be better than saliva in discriminating between patients and healthy controls, and between ART-naïve patients and those receiving therapy. Twenty-six metabolites were differentially altered in any or two types of samples. Our results suggest that urinary Neopterin, and plasma Choline and Sarcosine could be used as metabolic biomarkers of HIV/AIDS infection. Pathway analysis revealed significant alternations in 12 metabolic pathways. CONCLUSIONS: This study catalogs differentially regulated metabolites in biofluids, which helped classify subjects as healthy controls, HIV/AIDS patients, and those on ART. It also underscores the importance of further studying the consequences of HIV infection on host metabolism and its implications for pathogenesis.