Antiretroviral Therapy Guidelines Research Articles

Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand.

New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count. However, it is with an emphasis that commencing HAART at CD4 cell count above 500 cell/mm3 is for public health, in term of preventing HIV transmission and personal benefit. In tuberculosis co-infected patients with CD4 cell counts ≤50 cells/mm3 or with CD4 cell counts >50 cells/mm3 who have severe clinical disease, ART should be initiated within 2 weeks of starting tuberculosis treatment. The preferred initial ART regimen in treatment naïve patients is efavirenz combined with tenofovir and emtricitabine or lamivudine. Plasma HIV viral load assessment should be done twice a year until achieving undetectable results; and will then be monitored once a year. CD4 cell count should be monitored every 6 months until CD4 cell count ≥350 cells/mm3 and with plasma HIV viral load <50 copies/mL; then it should be monitored once a year afterward. HIV drug resistance genotypic test is indicated when plasma HIV viral load >1,000 copies/mL while on ART. Ritonavir-boosted lopinavir or atazanavir in combination with optimized two nucleoside-analogue reverse transcriptase inhibitors is recommended after initial ART regimen failure. Long-term ART-related safety monitoring has also been included in the guidelines.Electronic supplementary materialThe online version of this article (doi:10.1186/s12981-015-0053-z) contains supplementary material, which is available to authorized users.

Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy

The most recent version of the Southern African HIV Clinicians Society’s adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomized controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/μL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.

Geographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted HIV-1 drug resistance: an individual-patient- and sequence-level meta-analysis.

BackgroundRegional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes.Methods and FindingsWe reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four NNRTI SDRMs—K101E, K103N, Y181C, and G190A—accounted for >80% of NNRTI-associated TDR in all regions and subtypes. Sixteen nucleoside reverse transcriptase inhibitor (NRTI) SDRMs accounted for >69% of NRTI-associated TDR in all regions and subtypes. In SSA and SSEA, 89% of NNRTI SDRMs were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of NRTI SDRMs were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. Of 763 viruses with TDR in SSA and SSEA, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. Inherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling.ConclusionsMost TDR strains in SSA and SSEA arose independently, suggesting that ARV regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate TDR increases by reducing the generation of new ARV-resistant strains. A small number of NNRTI-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of TDR. In the context of a public health approach to ARV therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.

Recommendations for evaluation and management of bone disease in HIV.

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated.

Trends in and correlates of CD4+ cell count at antiretroviral therapy initiation after changes in national ART guidelines in Rwanda

Initiation of antiretroviral therapy (ART) in the advanced stages of HIV infection remains a major challenge in sub-Saharan Africa. This study was conducted to better understand barriers and enablers to timely ART initiation in Rwanda where ART coverage is high and national ART eligibility guidelines first expanded in 2007-2008. Using data on 6326 patients (≥15 years) at five Rwandan clinics, we assessed trends and correlates of CD4 cell count at ART initiation and the proportion initiating ART with advanced HIV disease (CD4 <200 cells/μl or WHO stage IV). Out of 6326 patients, 4486 enrolling in HIV care initiated ART with median CD4 cell count of 211 cells/μl [interquartile range: 131-300]. Median CD4 cell counts at ART initiation increased from 183 cells/μl in 2007 to 293 cells/μl in 2011-2012, and the proportion with advanced HIV disease decreased from 66.2 to 29.4%. Factors associated with a higher odds of advanced HIV disease at ART initiation were male sex [adjusted odds ratios (AOR) = 1.7; 95% confidence interval (CI): 1.3-2.1] and older age (AOR46-55+vs.<25 = 2.3; 95% CI: 1.2-4.3). Among those initiating ART more than 1 year after enrollment in care, those who had a gap in care of 12 or more months prior to ART initiation had higher odds of advanced HIV disease (AOR = 5.2; 95% CI: 1.2-21.1). Marked improvements in the median CD4 cell count at ART initiation and proportion initiating ART with advanced HIV disease were observed following the expansion of ART eligibility criteria in Rwanda. However, sex disparities in late treatment initiation persisted through 2011-2012, and appeared to be driven by later diagnosis and/or delayed linkage to care among men.

Implementation of antiretroviral therapy guidelines for under‐five children in Tanzania: translating recommendations into practice

IntroductionPaediatric antiretroviral therapy (ART) guidelines have been updated several times in recent years. We assessed implementation of ART guidelines among under-five children to inform the transition to universal paediatric ART in Tanzania.MethodsWe conducted a retrospective cohort analysis of infants (0 to 11 months) and children (12 to 59 months) enrolled between 2010 and 2012 using routinely collected data. Infants and children were initiated on ART according to the 2008 World Health Organization (WHO) recommendations/2009 Tanzania guidelines (universal ART for infants). Cumulative ART initiation incidence and correlates of ART initiation were examined using competing risk methods accounting for attrition (death or loss to follow-up). Kaplan-Meier methods and Cox regression models were used to examine attrition on ART and its correlates.ResultsA total of 1679 children were enrolled at 69 clinics: 469 (28%) infants and 1210 (74%) children. Infant cumulative ART initiation incidence was 59.6, 71.3 and 78.0% at one, three and six months of follow-up. Infants were more likely to start ART if enrolled in 2012 [adjusted sub-hazard ratio (AsHR)=2.2, 95% confidence interval (CI): 1.7 to 2.8] or 2011 (AsHR=1.8, 95% CI: 1.4 to 2.3) compared to 2010; they were more likely to start ART from prevention of mother-to-child HIV transmission (AsHR=1.6, 95% CI: 1.3 to 2.1) and inpatient wards (AsHR=1.5, 95% CI: 1.2 to 2.0) versus being enrolled from voluntary counselling and testing centres. Attrition at 12 months on ART was 33.9% and was more likely among infants with WHO Stage 4 [adjusted hazard ratio (AHR)=3.1. 95% CI: 1.8 to 5.2] and severe malnutrition (AHR=1.4, 95% CI: 1.0 to 1.9).Among 599 children eligible for ART at enrolment, cumulative ART initiation incidence was 51.8, 68.6 and 76.1% at one, three, and six months. Children were more likely to start ART if enrolled in 2012 (AsHR=1.8, 95% CI: 1.4 to 2.3) or 2011 (AsHR=1.5, 95% CI: 1.2 to 1.8) compared to 2010; they were more likely to start ART at primary health facilities (AsHR=1.5, 95% CI: 1.1 to 2.0) and less likely at urban facilities (AsHR=0.6, 95% CI: 0.5 to 0.9) and facilities without CD4 testing on site (AsHR=0.7, 95% CI: 0.5 to 0.9). Attrition at 12 months on ART was 23.1% and was more likely with severe malnutrition (AHR=1.8, 95% CI: 1.1 to 3.0), WHO Stage 4 (AHR=3.0, 95% CI: 1.0 to 8.5) and outpatient enrolees (AHR=1.7, 95% CI: 1.1 to 2.7).ConclusionsOur findings suggest the gradual adoption of guidelines over calendar time. Interventions to expedite ART initiation and support retention on ART are needed.

The Role of Therapeutic Drug Monitoring and Pharmacogenetic Testing in the Management of HIV Infection: A Review

One of the less acknowledged tools in the international guidelines of combination antiretroviral therapy (cART) for HIV-1 infection is therapeutic drug monitoring (TDM). Yet anywhere there is a Clinical Pharmacology Unit or other facility for measuring plasma drug concentrations, physicians often measure the plasma levels of antiretrovirals as well as of comedications and find it useful. The aim of this article is to provide an overview of how relevant it is for a clinician to assess individual drug levels. Moreover we wanted to investigate to what extent the field is already assisted by web-based tools (i.e.: drug interaction charts). Finally we tried to look how pharmacogenetics may reduce the need for TDM, and whether this diagnostics is cost-effective. We searched PubMed by “drug interactions and HIV”, “drug level and HIV”, “therapeutic drug monitoring”, and we investigated the Liverpool Drug Interaction website, the DHHS Guidelines website, the UCSF website, and the AETC online Guide for HIV/AIDS Clinical care. Furthermore, we assessed the role that the main national and international guidelines for antiretroviral treatment attributed to TDM and searched for the various clinical subsets in which drug monitoring is particularly relevant. Finally, we suggest that cross-sectional studies of subjects failing therapy or experiencing drug-related adverse events, as well as longitudinal studies of particular conditions, may show the importance of problem-targeted rather than routine TDM.

Baseline Laboratory Profile of HIV Positive Patients on Antiretroviral Therapy in Jos North Central Nigeria: Implications for Pre-vention, Treatment, Care and Support

Background: We characterized baseline laboratory data of patients to identify priority treatment areas, most affected populations, anticipated clinical complications and assessed the potential burden of retention in care in Jos, Plateau State—North Central Nigeria. Methods: This study was a cross-sectional design from January 2004 to December 2005 at Faith Alive Foundation (FAF). All participants were HIV-positive and underwent pre-antiretroviral therapy counseling based on the national antiretroviral therapy (ART) guidelines and baseline laboratory testing. Data were captured on Microsoft Excel, validated on Epi Info and analyzed on SPSS version 21 at P < .05 level of significance. Results: Total of 1499 (463 men and 1036 women) participants were evaluated in this study. The age and sex related distribution of participants showed that majority (80.3% for males and 92.5% for females) were 16 - 45 years old. Amylase and creatinine were significantly higher in males than females (P = .02). Anaemia was the most common baseline abnormality (63% for females and 58% for males), while baseline CD4 count was significantly lower in males than females (P < .02) and at one-third had elevated liver enzymes (AST and ALT). Conclusion: The baseline laboratory profile of most HIV positive patients in Jos and environs of North Central–Nigeria was characterized by anaemia, elevated creatinine, and abnormal liver transaminase levels (AST and ALT). This pre-ART laboratory result suggests that HIV-positive individuals have multiple clinical abnormalities which may require more extensive care than just treating the HIV disease.

Moving past the 'pre-treatment' era of HIV care.

In 2003, the World Health Organization (WHO) first published human immunodeficiency virus (HIV) antiretroviral therapy (ART) guidelines, recommending treatment for persons with a CD4 count ⩽200 cells/mm3. Shortly thereafter, the Global Fund and the President's Emergency Plan for AIDS Relief took the first steps towards what has become a massive scale-up of ART to over 12 million people worldwide, arguably the greatest public health achievement of our generation. These events ushered in a welcomed new phase of the epidemic in low-income countries, with significant reductions in HIV-related mortality and increased life expectancy for those infected.1 However, whereas provision of ART to those who met the criteria provided demonstrable benefits, these same criteria necessarily dichotomized HIV treatment services between those who got it and those who watched, waited, and, more often than not, wandered away. Countless studies have documented staggering rates of attrition from HIV care between HIV testing and ART eligibility across the African continent, and beyond.2 In this issue of Public Health Action, Shankar and colleagues present rare programmatic data on pre-treatment loss to follow-up from India.3 Among a cohort of approximately 700 patients who did not meet the criteria for ART initiation at the time of initial presentation, only approximately 60% were retained in HIV care at 12 months. Perhaps not surprisingly, unmarried patients, those residing in rural areas, and those with Stage III or IV disease but who did not meet national treatment criteria (presumably with tuberculosis coinfection) were more likely to be lost from care. Future studies from the Indian sub-continent should build upon these findings by elucidating outcomes and reasons for loss among those not retained. Prior reports describing the costs of transportation and ancillary services, persistent stigmatizing attitudes towards HIV, overburdened clinics and health care professionals who provide heroic but limited pre-treatment care, have taught us that the pre-therapy period is one of the most vulnerable for people living with HIV. These data add to an ongoing debate within the global HIV community about whether to eradicate thresholds for ART initiation. The benefits of early therapy are indisputable. Numerous studies have demonstrated both improved AIDS-related and non-AIDS-related morbidity and mortality with earlier initiation of ART.4 As of 2013, the US guidelines adopted a ‘treatment for all’ strategy, and both the European guidelines and updated WHO guidelines now recommend therapy for all patients with a CD4 count ⩽500 cells/mm3. While we await the results of the START study to learn more about the risks and benefits of very early therapy, as well as results from numerous community-based ‘test and treat’ studies, it is increasingly clear that a significant proportion of patients cannot afford to wait any longer after arriving at an HIV clinic with a diagnosis in hand. Even with point-of-care CD4 count testing, numerous barriers to expedited therapy continue, and the cascade of HIV care remains dangerously steep.5,6 Removing all steps between testing and treatment will serve as a crucial life raft to millions at risk for this fall, and bring us closer to the next phase of the epidemic, one with exceedingly rare pre-treatment losses from care.

The effect of adherence to guidelines for initial antiretroviral therapy on 1-year outcomes: a French cohort study.

BackgroundGuidelines for antiretroviral treatment (cART) are published regularly, but there is little information regarding the effect of adherence to guidelines on patient outcomes. We assessed the effect of following the "when-to-start" and "what-to-start" guidelines, on treatment modifications, and on immunological and virological outcome at 12 months in a cohort of HIV-1 infected patients initiating cART from 2000 to 2010.MethodsConsecutive HIV-1 infected patients, antiretroviral naive, initiating cART from 2000 to 2010 at a University Hospital were enrolled. HIV-2 infection, cART for prevention of mother-to-child transmission or during primary HIV-infection and unlicensed drugs were excluded. The respect or not of the "when-to-start" and "what-to-start" guidelines was based on French guidelines published from 2000 to 2010. Factors associated with cART modifications at 12 months and factors associated with an HIV viral load of <50 copies/mL at 12 months were assessed by univariate and multivariate logistic regression modeling. Variations in CD4 counts from baseline were assessed by univariate and multivariate linear regression.ResultsOf 1365 patients starting cART, 151 were treated outside "when-to-start" guidelines and 150 were treated outside "what-to-start" guidelines. Not using "when-to-start" guidelines was mainly related to early initiation in young men having sex with men, and was not associated with a significantly different outcome at 12 months. Treatments that did not follow "what-to-start" guidelines were not observed in any specific population and were associated with more treatment modifications and a poorer virological outcome at 12 months.ConclusionsAdherence to "what-to-start" guidelines is associated with a better outcome at 12 months in HIV-infected patients initiating antiretroviral therapy. Efforts should be made to promote adherence to these guidelines.

Clinician Perspectives on Delaying Initiation of Antiretroviral Therapy for Clinically Eligible HIV-Infected Patients.

Objectives:Guidelines for antiretroviral therapy (ART) initiation have evolved, but consistently note that adherence problems should be considered and addressed. Little is known regarding the reasons providers delay ART initiation in clinically eligible patients.Methods:In 2009, we surveyed a probability sample of HIV care providers in 582 outpatient facilities in the United States and Puerto Rico with an open-ended question about nonclinical reasons for delaying ART initiation in otherwise clinically eligible patients.Results:Very few providers (2%) reported never delaying ART. Reasons for delaying ART were concerns about patient adherence (68%), patient acceptance (60%), and structural barriers (33%). Provider and practice characteristics were associated with reasons for delaying ART.Conclusion:Reasons for delaying ART were consistent with clinical guidelines and were both patient level and structural. Providers may benefit from training and access to referrals for ancillary services to enhance their ability to monitor and address these issues with their patients.

How can we get close to zero? The potential contribution of biomedical prevention and the investment framework towards an effective response to HIV.

BackgroundIn 2011 an Investment Framework was proposed that described how the scale-up of key HIV interventions could dramatically reduce new HIV infections and deaths in low and middle income countries by 2015. This framework included ambitious coverage goals for prevention and treatment services resulting in a reduction of new HIV infections by more than half. However, it also estimated a leveling in the number of new infections at about 1 million annually after 2015.MethodsWe modeled how the response to AIDS can be further expanded by scaling up antiretroviral treatment (ART) within the framework provided by the 2013 WHO treatment guidelines. We further explored the potential contributions of new prevention technologies: ‘Test and Treat’, pre-exposure prophylaxis and an HIV vaccine.FindingsImmediate aggressive scale up of existing approaches including the 2013 WHO guidelines could reduce new infections by 80%. A ‘Test and Treat’ approach could further reduce new infections. This could be further enhanced by a future highly effective pre-exposure prophylaxis and an HIV vaccine, so that a combination of all four approaches could reduce new infections to as low as 80,000 per year by 2050 and annual AIDS deaths to 260,000.InterpretationIn a set of ambitious scenarios, we find that immediate implementation of the 2013 WHO antiretroviral therapy guidelines could reduce new HIV infections by 80%. Further reductions may be achieved by moving to a ‘Test and Treat’ approach, and eventually by adding a highly effective pre-exposure prophylaxis and an HIV vaccine, if they become available.

Effectiveness of Early Infant Diagnosis (EID) in Detecting the Serostatus of HIV-Exposed Infants and Children.

Although interventions to prevent mother-to-child transmission of HIV infection are being increasingly implemented as a part of national guideline, the prevalence of pediatric HIV remains high. There is remarkable increase in survival if HIV-infected children have access to early infant diagnosis (EID) and treatment. The study was conducted in the Department of Obstetrics and Gynecology Medical College, Kolkata from July 2011 to February 2014 after obtaining approval from the institutional ethics committee. All the infants of HIV-positive mothers who came for EID between 6weeks to 18months of age during the study period were included in the study. A total number of 151 infants were included in the study and divided into Group A and B according to the time of first testing. It was a prospective observational longitudinal study. Data were collected from the EID register of PPTCT unit Medical College Kolkata. EID was done as laid out in the pediatric ART (anti-retroviral therapy) guidelines of the National AIDS Control Organization. Effectiveness of EID is judged by the corroboration of results at 6week, 6 and 18 months. Comparing the results in group A, we found that 10.26, 8.41, and 7.29% were positive at 6weeks, 6 and 18months, respectively, and with p value of 0.5828 the differences were not statistically significant. In group B, we observed that 47.06 and 45.45% were positive at 6 and 18months, respectively. Analysis revealed a p value of 0.9072 indicating no significant statistical difference between the results of testing in different periods. This reflects a good correlation between the 6weeks, 6 and 18 months value, thus establishing the integrity of the EID. Ultimate integrity of the PPTCT is judged by testing the child. EID is a novel procedure which aims at earlier diagnosis and initiation of treatment in the children.

The Impact of the 2013 WHO Antiretroviral Therapy Guidelines on the Feasibility of HIV Population Prevention Trials

Background: Several cluster-randomized HIV prevention trials aim to demonstrate the population-level preventive impact of antiretroviral therapy (ART). 2013 World Health Organization (WHO) guidelines raising the ART initiation threshold to CD4 <500/µL could attenuate these trials’ effect size by increasing ART usage in control clusters. Methods: We used a computational model to simulate strategies from a hypothetical cluster-randomized HIV prevention trial. The primary model outcome was the relative reduction in 24-month HIV incidence between control (ART offered with CD4 below threshold) and intervention (ART offered to all) strategies. We assessed this incidence reduction using the revised (CD4 <500/µL) and prior (CD4 <350/µL) control ART initiation thresholds. Additionally, we evaluated changes to trial characteristics that could bolster the incidence reduction. Results: With a control ART initiation threshold of CD4 <350/µL, 24-month HIV incidence under control and intervention strategies was 2.46/100 person-years (PY) and 1.96/100 PY, a 21% reduction. Raising the threshold to CD4 <500/µL decreased the incidence reduction by more than one-third, to 12%. Using this higher threshold, moving to a 36-month horizon (vs 24-month), yearly control-strategy HIV screening (vs bian-nual), and intervention-strategy screening every 2 months (vs biannual), resulted in a 31% incidence reduction that was similar to effect size projections for ongoing trials. Alternate assumptions regarding cross-cluster contamination had the greatest influence on the incidence reduction. Conclusions: Implementing the 2013 WHO HIV treatment threshold could substantially diminish the incidence reduction in HIV population prevention trials. Alternative HIV testing frequencies and trial horizons can bolster this incidence reduction, but they could be logistically and ethically challenging. The feasibility of HIV population prevention trials should be reassessed as the implementation of treatment guidelines evolves.

The Impact of the 2013 WHO Antiretroviral Therapy Guidelines on the Feasibility of HIV Population Prevention Trials

The Impact of the 2013 WHO Antiretroviral Therapy Guidelines on the Feasibility of HIV Population Prevention Trials

Realizing the potential of treatment as prevention: global ART policy and treatment coverage.

This article reviews the antiretroviral therapy (ART) initiation criteria from published national guidelines for 94 countries (representing 86 % of global HIV burden) and compares them with the 2013 World Health Organization (WHO) ART guidelines. As of 31st of July 2014, 19 countries have adopted the WHO-recommended CD4 eligibility criteria of ≤500cells/mm(3), while seven have opted to treat irrespective of CD4 cell count ("test and treat"). Together, these 26 countries represent 27% of 2013 global HIV burden. Additionally, test and treat is recommended for selected groups of HIV-positive individuals, namely, (a) people with tuberculosis in 58 countries, (b) pregnant women in 42 countries, (c) people with liver disease due to hepatitis B co-infection in 52 countries, (d) serodiscordant couples in 35 countries and (e) children below 5years in nine countries. Global access to treatment has improved; however in 2013, ART coverage was 12.9 million or 37% of people living with HIV. Rapidly translating new science into policy is a critical component of the HIV response. Adapting and implementing the 2013 WHO treatment recommendations are necessary to prevent unnecessary illness, death, HIV transmission and costs.

How many people living with HIV will be additionally eligible for antiretroviral treatment in Karnataka State, India as per the World Health Organization 2013 guidelines?

BackgroundThe National AIDS control programme (NACP) in India is currently following the World Health Organization (WHO) 2010 antiretroviral therapy (ART) guidelines. In 2013, the WHO revised its recommendations for initiating ART among people living with HIV (PLHIV) by increasing the threshold for ART initiation to a CD4 count ≤500 cells/uL. For certain patient groups, ART is recommended irrespective of CD4 count (PLHIV with active tuberculosis, hepatitis B virus infection, pregnant and breast feeding women, children aged under five years and those living in a sero-discordant relationship). In this operational research, we assess the effect of applying this recommendation on the number of PLHIV additionally eligible for ART.MethodsThis was a cross-sectional analysis of routinely collected programme data from all PLHIV registered in Karnataka State (population 60 million), India in 2012.ResultsOf 37,044 PLHIV, 27,074 (73%) were eligible for initiating ART as per WHO-2010 criteria. As per the WHO-2013 criteria (CD4 count ≤500 and all pregnant women and under-five children irrespective of CD4 count), an additional 5104 (14%) HIV-infected people would be eligible for initiating ART. There were no data to inform the additional patient load due to sero-discordance.ConclusionAdopting the WHO-2013 guidelines for India has important resource implications. However, given the significant patient and programmatic benefits of adopting the new guidelines, this has been considered favourably by the NACP in India and steps are being planned to integrate ART care into the general health system to cope with the increased numbers of patients.

Costs and cost-efficacy analysis of the 2014 GESIDA/Spanish National AIDS Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults

IntroductionGESIDA and the National AIDS Plan panel of experts suggest preferred (PR) and alternative (AR) regimens of antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2014. The objective of this study is to evaluate the costs and the efficiency of initiating treatment with these regimens. MethodsAn economic assessment was made of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied by considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and costs correspond to those of 2014. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. ResultsIn the base case scenario, the cost of initiating treatment ranges from 5133 Euros for ABC/3TC+EFV to 11,949 Euros for TDF/FTC+RAL. The efficacy varies between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.89 for TDF/FTC/EVG/COBI. Efficiency, in terms of cost/efficacy, ranges from 7546 to 13,802 Euros per responder at 48 weeks, for ABC/3TC+EFV and TDF/FTC+RAL respectively. ConclusionConsidering ART official prices, the most efficient regimen was ABC/3TC+EFV (AR), followed by the non-nucleoside containing PR (TDF/FTC/RPV and TDF/FTC/EFV). The sensitivity analysis confirms the robustness of these findings.

WHO guidelines for antiretroviral therapy in serodiscordant couples in sub-Saharan Africa: how many fit?

To evaluate the implication of WHO guidelines for serodiscordant couples, we interviewed HIV-infected adults on their partner's serostatus. We found that 12% with more than 500 CD4+ cells/μl should be recommended antiretroviral treatment (ART) because their partner was seronegative; 24% could be recommended not to start ART because their partner was seropositive; and 64% could not be given any recommendation regarding ART early initiation because they had either no stable partnership (30%) or were in a stable partnership with a partner whose status they were not aware of (34%).

Documento de consenso de GeSIDA/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (Actualización enero 2014)

ObjectiveThis consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients. MethodsTo formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America. ResultsIn this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: <350cells/μL, A-I; 350-500 cells/μL, A-II, and >500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer). ConclusionsThese new guidelines updates previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated.