Articles tagged as "Hong Kong Special Administrative Region of China"

Technology for tuberculosis, but why can’t we simply prevent it with proven tools that save lives?

Editor’s notes: Advances in diagnostic test technology have transformed the management of HIV and related infections.  For HIV, we have seen the introduction of self-administered test kits as well as new approaches to HIV viral load testing and nucleic acid based infant diagnosis.  Cryptococcal antigen screening can make prophylaxis and treatment more focused and potentially cost-effective.  For tuberculosis the biggest revolution has been the widespread introduction of the geneXpert® system.  The newest version, the Xpert® Ultra, is more sensitive than the original cartridge and is now being scaled up in countries including South Africa.  Agizew and colleagues conducted a study in Botswana to compare how the Xpert® MTB/RIF cartridge performed when used in centralized or peripheral health facilities.  Encouragingly there were few differences between the two levels, suggesting that the systems can be used close to the point of care.  However, the authors did note a surprisingly high level of unsuccessful tests (15%) both at the central lab and at the peripheral clinic.  Many of these test failures seem to have been because the sample was not processed correctly, and so should be amenable to better training for the health care workers performing the test.  The yield of testing varied greatly between the 13 sites. Between 1% and 23% of samples were positive for tuberculosis, with an average of 14%.  This may be because some sites were receiving specialized referrals.  Of the 447 positive samples, 8% were shown to be rifampicin resistant.  This figure is hard to interpret without more detail of the sample of patients in whom the test was performed.  Resistance is always higher among those who have been treated previously and may be higher in those referred to specialized centres.  Nonetheless, it demonstrates that there are a significant number of people with tuberculosis in Botswana who are very likely to have multi-drug resistant disease and need effective second line treatment.  Technology comes with a price tag.  In this study, the team bought test kits for $18 each, which makes it an expensive choice.  However, if it leads to prompt treatment of multi-drug resistant disease and more accurate diagnosis of tuberculosis, including among those living with HIV, this might still be cost-effective.

A small implementation research study from a single provincial referral centre in Zambia also examined the use and results of geneXpert® screening.  Masenga and colleagues found that 6.6% of 2374 samples tested by geneXpert® over the course of a year were positive for tuberculosis.  An additional 1301 samples were tested by sputum microscopy.  Their results suggest that geneXpert® was used mainly on people who were living with HIV, given that more than 90% of the positive samples came from people living with HIV.  5.9% of the 152 positive samples that were tested in the system were resistant to rifampicin, with no difference by gender.  This study leaves many questions unanswered, such as the sampling strategy, the history of previous treatment and the outcomes of the diagnosis in terms of treatment regimen and success.  However, it shines a light on the ways that new technology is now routine in some settings.  We need more research from diverse settings to paint the full picture of implementation outside traditional research centres.

Zenner and colleagues revisit the question of the risks and benefits of treatment for latent tuberculosis infection.  In a systematic review and network meta-analysis, they demonstrate once more that we have several effective ways to prevent tuberculosis among people living with HIV and that the harms are much smaller than the risks.  The question remains why we have failed so badly to scale up preventive therapy for tuberculosis alongside the success in scale up of antiretrovirals.

 

Peripheral clinic versus centralized laboratory-based XPERT® MTB/RIF performance: experience gained from a pragmatic, stepped-wedge trial in Botswana

Agizew T, Boyd R, Ndwapi N, Auld A, Basotli J, Nyirenda S, Tedla Z, Mathoma A, Mathebula U, Lesedi C, Pals S, Date A, Alexander H, Kuebrich T, Finlay A. PLoS One. 2017 Aug 17;12(8):e0183237. doi: 10.1371/journal.pone.0183237. eCollection 2017.

Background: In 2011, the Botswana National Tuberculosis Program adopted World Health Organization guidelines and introduced Xpert® MTB/RIF (Xpert®) assay to support intensified case finding among people living with HIV enrolling in care. An evaluation was designed to assess performance under operational conditions to inform the national Xpert® scale-up.

Methods: Xpert® was implemented from August 2012 through November 2014 with 13 GeneXpert® instruments (GeneXpert®) deployed in a phased approach over nine months: nine centralized laboratory and four point-of-care (POC) peripheral clinics. Clinicians and laboratorians were trained on the four-symptom tuberculosis screening algorithm and Xpert® testing. We documented our experience with staff training and GeneXpert® performance. Test results were extracted from GeneXpert® software; unsuccessful tests were analysed in relation to testing sites and trends over time.

Results: During 276 instrument-months of operation a total of 3630 tests were performed, of which 3102 (85%) were successful with interpretable results. Mycobacterium tuberculosis complex was detected for 447 (14%); of these, 36 (8%) were rifampicin resistant. Of all 3630 Xpert® tests, 528 (15%) were unsuccessful; of these 361 (68%) were classified as "error", 119 (23%) as "invalid" and 48 (9%) as "no result". The total number of recorded error codes was 385 and the most common reasons were related to sample processing (211; 55%) followed by power supply (77; 20%) and cartridge/module related (54; 14%). Cumulative incidence of unsuccessful test was similar between POC (17%, 95% CI: 11-25%) and centralized laboratory-based GeneXpert® instruments (14%, 95% CI: 11-17%; p = 0.140).

Conclusions: Xpert® introduction was successful in the Botswana setting. The incidence of unsuccessful test was similar by GeneXpert® location (POC vs. centralized laboratory). However, unsuccessful test incidence (15%) in our settings was higher than previously reported and was mostly related to improper sample processing. Ensuring adequate training among Xpert® testing staff is essential to minimize errors.

Abstract  Full-text [free] access

Rifampicin resistance in mycobacterium tuberculosis patients using GeneXpert® at Livingstone Central Hospital for the year 2015: a cross sectional explorative study

Masenga SK, Mubila H, Hamooya BM. BMC Infect Dis. 2017 Sep 22;17(1):640. doi: 10.1186/s12879-017-2750-9

Background: Since the recent introduction of GeneXpert® for the detection of Tuberculosis (TB) drug resistance mutations in both primary resistance and acquired resistance in Zambia, little has been documented in literature on the issue of rifampicin resistance especially in the face of a high National TB burden. The study aimed to determine the prevalence of rifampicin resistance in tuberculosis patients at Livingstone Central Hospital for the year 2015.

Methods: This was a cross sectional study conducted at Livingstone Central Hospital where we reviewed 152 records (from January 1, 2015 to 31st December 2015) involving patients who presented with clinically suspected TB or documented TB, whose samples were sent to the laboratory for GeneXpert® Mycobacterium tuberculosis/rifampicin testing. Statistical evaluations used a one-sample test of proportion and Fisher's exact test.

Results: The age of participants ranged from 8 months to 73 years old (median = 34). Of the participants with complete data on gender, 99 (66%) and 52 (34%) were males and females respectively. The TB co-infection with HIV prevalence was 98.3% (p < 0.001). Prevalence of rifampicin resistance was 5.9% and there was no statistical significant difference between being male or female (p = 0.721).

Conclusion: We were able to show from our study, evidence of rifampicin resistance at Livingstone Central Hospital. Hence, there was need for further in-depth research and appropriate interventions (i.e. close follow-up and patient care for drug resistance positive patients).

Abstract  Full-text [free] access

Treatment of latent tuberculosis infection: an updated network meta-analysis

Zenner D, Beer N, Harris RJ, Lipman MC, Stagg HR, van der Werf MJ.  Ann Intern Med. 2017 Aug 15;167(4):248-255. doi: 10.7326/M17-0609. Epub 2017 Aug 1.

Background: Treatment of latent tuberculosis infection (LTBI) is an important component of tuberculosis (TB) control, and this study updates a previous network meta-analysis of the best LTBI treatment options to inform public health action and programmatic management of LTBI.

Purpose: To evaluate the comparative efficacy and harms of LTBI treatment regimens aimed at preventing active TB among adults and children.

Data sources: PubMed, Embase, and Web of Science from indexing to 8 May 2017; clinical trial registries; and conference abstracts. No language restrictions were applied.

Study selection: Randomized controlled trials that evaluated human LTBI treatments and recorded at least 1 of 2 prespecified end points (hepatotoxicity and prevention of active TB).

Data extraction: 2 investigators independently extracted data from eligible studies and assessed study quality according to a standard protocol.

Data synthesis: The network meta-analysis of 8 new and 53 previously included studies showed that isoniazid regimens of 6 months (odds ratio [OR], 0.65 [95% credible interval {CrI}, 0.50 to 0.83]) or 12 to 72 months (OR, 0.50 [CrI, 0.41 to 0.62]), rifampicin-only regimens (OR, 0.41 [CrI, 0.19 to 0.85]), rifampicin-isoniazid regimens of 3 to 4 months (OR, 0.53 [CrI, 0.36 to 0.78]), rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35 [CrI, 0.19 to 0.61]), and rifampicin-pyrazinamide regimens (OR, 0.53 [CrI, 0.33 to 0.84]) were efficacious compared with placebo. Evidence existed for efficacy of weekly rifapentine-isoniazid regimens compared with no treatment (OR, 0.36 [CrI, 0.18 to 0.73]). No conclusive evidence showed that HIV status altered treatment efficacy.

Limitation: Evidence was sparse for many comparisons and hepatotoxicity outcomes, and risk of bias was high or unknown for many studies.

Conclusion: Evidence exists for the efficacy and safety of 6-month isoniazid monotherapy, rifampicin monotherapy, and combination therapies with 3 to 4 months of isoniazid and rifampicin.

Abstract  Full-text [free] access

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Tenofovir resistance – need for caution but not panic

Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study.

TenoRes Study Group. Lancet Infect Dis. 2016 Jan 28. pii: S1473-3099(15)00536-8. doi: 10.1016/S1473-3099(15)00536-8. [Epub ahead of print]

Background: Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART.

Methods: The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.

Findings: We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for CD4 cell count <100 cells per µL). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]).

Interpretation: We recorded drug resistance in a high proportion of patients after virological failure on a tenofovir-containing first-line regimen across low-income and middle-income regions. Effective surveillance for transmission of drug resistance is crucial.

Abstract  Full-text [free] access 

Editor’s notes: Global surveillance for tenofovir (TDF) resistance is important at a time of expanding use of TDF-containing regimens for treatment and prevention. This collaborative analysis used data collated from several small studies in different settings. Overall, around one in three people who had failed on TDF-containing treatment had evidence of TDF resistance, although this frequency varied between 20% in Europe to almost 60% in Africa. Mutations associated with NNRTIs and lamivudine/emtricitabine resistance were more common overall and were present in most people with TDF resistance.

The regional variation probably reflects differences in clinical practice and study inclusion criteria. All European studies involved cohorts with frequent viral load monitoring, whereas half of the African cohorts had no routine viral load monitoring. All European studies included people with virologic failure but with low-level viraemia (viral load <1000 copies/ml) whereas almost all African studies included only people with viral load >1000 copies/ml.

While these data provide useful estimates of the frequency of drug resistance mutations in people with virologic failure on first-line ART, there should be caution about extrapolating beyond this. Reports from cohort studies with an accurate denominator of all people starting TDF-containing first-line ART would be useful to give more reliable estimates of overall incidence of acquired TDF resistance. Moreover, there remains a need for representative population-based surveillance for acquired and transmitted drug resistance. So far, global surveillance has detected limited evidence of transmitted TDF-associated mutations, but this needs to be monitored closely, especially in high incidence settings.

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HIV-associated stigma may impede HIV medication adherence among people living with HIV

The association of HIV-related stigma to HIV medication adherence: a systematic review and synthesis of the literature.

Sweeney SM, Vanable PA. AIDS Behav. 2015 Aug 25. [Epub ahead of print]

This paper provides a review of the quantitative literature on HIV-related stigma and medication adherence, including: (1) synthesis of the empirical evidence linking stigma to adherence, (2) examination of proposed causal mechanisms of the stigma and adherence relationship, and (3) methodological critique and guidance for future research. We reviewed 38 studies reporting either cross-sectional or prospective analyses of the association of HIV-related stigma to medication adherence since the introduction of antiretroviral therapies (ART). Although there is substantial empirical evidence linking stigma to adherence difficulties, few studies provided data on psychosocial mechanisms that may account for this relationship. Proposed mechanisms include: (a) enhanced vulnerability to mental health difficulties, (b) reduction in self-efficacy, and (c) concerns about inadvertent disclosure of HIV status. Future research should strive to assess the multiple domains of stigma, use standardized measures of adherence, and include prospective analyses to test mediating variables.

Abstract access 

Editor’s notes: People living with HIV often experience stigma and discrimination including social isolation and negative stereotyping. Recent evidence suggests that stigma may influence adherence to HIV medication among people living with HIV. This paper presents findings from a systematic review of the evidence on the impact of HIV-associated stigma on HIV medication adherence. The authors identified 38 studies which quantitatively assessed the association between stigma and medication adherence. All studies found evidence indicating that stigma contributed to adherence difficulties among people living with HIV. Included studies looked at diverse patient populations sampled from different countries and contexts. While stigma is heavily influenced by the socio-cultural context, the association between stigma and adherence across diverse contexts indicates that there may be commonalities in what causes stigma and how this relates to adherence.

The authors of this review suggest three possible causal mechanisms of HIV-associated stigma and medication adherence: (1) There may be links between stigma and depressive symptoms, and between depressive symptoms and adherence. Internalized stigma may enhance vulnerability to depressive symptoms, and this may influence adherence to HIV medication. (2) Stigma may cause reductions in self-efficacy – a person’s judgment of his or her ability to organize and execute behaviours - which may influence medication adherence. (3) People may fear HIV status disclosure by being seen taking HIV medication. Fear of status disclosure, and associated stigma, may cause people to avoid taking HIV medication.

The studies included in this review indicate a clear link between HIV-associated stigma and HIV medication adherence. There may be commonalities in what causes stigma across multiple populations. Future research should assess the influence of multiple forms of stigma on adherence, and on testing causal mechanisms between stigma and adherence. 

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Increasing transmitted resistance to antiretroviral therapy in low/middle-income countries - highest prevalence in MSM

Global burden of transmitted HIV drug resistance and HIV-exposure categories: a systematic review and meta-analysis.

Pham QD, Wilson DP, Law MG, Kelleher AD, Zhang L. AIDS. 2014 Nov 28;28(18):2751-62. doi: 10.1097/QAD.0000000000000494.

Objectives: Our aim was to review the global disparities of transmitted HIV drug resistance (TDR) in antiretroviral-naive MSM, people who inject drugs (PWID) and heterosexual populations in both high-income and low/middle-income countries.

Design/methods: We undertook a systematic review of the peer-reviewed English literature on TDR (1999-2013). Random-effects meta-analyses were performed to pool TDR prevalence and compare the odds of TDR across at-risk groups.

Results: A total of 212 studies were included in this review. Areas with greatest TDR prevalence were North America (MSM: 13.7%, PWID: 9.1%, heterosexuals: 10.5%); followed by western Europe (MSM: 11.0%, PWID: 5.7%, heterosexuals: 6.9%) and South America (MSM: 8.3%, PWID: 13.5%, heterosexuals: 7.5%). Our data indicated disproportionately high TDR burdens in MSM in Oceania (Australia 15.5%), eastern Europe/central Asia (10.2%) and east Asia (7.8%). TDR epidemics have stabilized in high-income countries, with a higher prevalence (range 10.9-12.6%) in MSM than in PWID (5.2-8.3%) and heterosexuals (6.4-9.0%) over 1999-2013. In low/middle-income countries, TDR prevalence in all at-risk groups in 2009-2013 almost doubled than that in 2004-2008 (MSM: 7.8 vs. 4.2%, P = 0.011; heterosexuals: 4.1 vs. 2.6%, P < 0.001; PWID: 4.8 vs. 2.4%, P = 0.265, respectively). The risk of TDR infection was significantly greater in MSM than that in heterosexuals and PWID. We observed increasing trends of resistance to non-nucleoside reverse transcriptase and protease inhibitors among MSM.

Conclusion: TDR prevalence is stabilizing in high-income countries, but increasing in low/middle-income countries. This is likely due to the low, but increasing, coverage of antiretroviral therapy in these settings. Transmission of TDR is most prevalent among MSM worldwide.

Abstract access 

Editor’s notes: HIV mutates very rapidly, and many early antiretroviral agents had a low genetic barrier to the development of resistance. Thus the emergence of virus resistant to antiretroviral agents, particularly to early drug classes, was inevitable. Surveillance for drug-resistant virus among people with no prior history of taking antiretroviral drugs (transmitted drug resistance) is essential to monitor the spread of drug resistance at population level.

This systematic review aimed to compare transmitted drug resistance in different geographical regions and between subpopulations of HIV-positive people by likely route of transmission. Transmitted resistance was most prevalent in high income settings. This is not surprising given wide use of suboptimal drug regimens before effective triple therapy was available. Reassuringly, the prevalence of transmitted resistance seems to have stabilised in high-income settings. The increase in transmitted resistance in low and middle income countries is of more concern. It is not surprising, given that first-line regimens comprising two nucleoside reverse transcriptase inhibitors and a non-nucleoside reverse transcriptase inhibitor are vulnerable to the development of resistance if the drug supply is interrupted or adherence is suboptimal. In addition, if viral load monitoring is not available, people remain on failing drug regimens for longer, and thus have more risk of transmitting resistant virus.

Within the subpopulations examined in this review, transmitted resistance was consistently higher in men who have sex with men, suggesting that resistance testing prior to treatment is particularly valuable for this population.

Limitations of the review include exclusion of studies that did not compare transmitted resistance between the specified subpopulations, and small sample size in many subgroups.

Continued surveillance for transmitted drug resistance is critical. This is most important in settings where individualised resistance testing is not available. This will ensure that people starting antiretroviral therapy receive treatment that will suppress their viral load effectively. Wider use of viral load monitoring, combined with access to effective second and third line regimens, will also help limit spread of drug resistance.

HIV Treatment
Angola, Argentina, Australia, Austria, Belgium, Benin, Botswana, Brazil, Burkina Faso, Cambodia, Cameroon, Canada, Central African Republic, Chad, China, Côte d'Ivoire, Croatia, Cuba, Cyprus, Denmark, Dominican Republic, El Salvador, Estonia, Ethiopia, France, Gabon, Georgia, Germany, Greece, Guatemala, Honduras, Hong Kong Special Administrative Region of China, Hungary, India, Indonesia, Ireland, Israel, Italy, Japan, Kazakhstan, Kenya, Latvia, Malawi, Malaysia, Moldova, Mozambique, Netherlands, Peru, Philippines, Poland, Portugal, Republic of Korea, Romania, Russia, Rwanda, Slovenia, South Africa, Spain, Swaziland, Sweden, Switzerland, Taiwan, Thailand, Uganda, United Kingdom of Great Britain and Northern Ireland, United Republic of Tanzania, United States of America, Viet Nam, Zambia, Zimbabwe
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Efavirenz dose reduction could help scale up antiretroviral therapy access

Efficacy of 400 mg efavirenz versus standard 600 mg dose in HIV-infected, antiretroviral-naive adults (ENCORE1): a randomised, double-blind, placebo-controlled, non-inferiority trial.

ENCORE1 Study Group. Lancet. 2014 Feb 7. pii: S0140-6736(13)62187-X. doi: 10.1016/S0140-6736(13)62187-X. [Epub ahead of print]

Background: The optimum dose of key antiretroviral drugs is often overlooked during product development. The ENCORE1 study compared the efficacy and safety of reduced dose efavirenz with standard dose efavirenz in combination with tenofovir and emtricitabine as first-line treatment for HIV infection. An effective and safe reduced dose could yield meaningful cost savings.

Methods: ENCORE1 is a continuing non-inferiority trial in HIV-1-infected antiretroviral-naive adults in 38 clinical sites in 13 countries. Participants (plasma HIV-RNA >1000 log10 copies per mL, CD4 T-cell count 50-500 cells per µL) were randomly assigned by a computer-generated sequence with a blocking factor of four (stratified by clinical site and by screening viral load) to receive tenofovir plus emtricitabine with either a reduced daily dose (400 mg) or a standard dose (600 mg) of efavirenz. Participants, physicians, and all other trial staff were masked to treatment group. The primary endpoint was the difference in proportions of participants with plasma HIV-RNA of less than 200 copies per mL at 48 weeks. Treatment groups were regarded as non-inferior if the lower limit of the 95% CI for the difference in viral load was less than -10% by modified intention-to-treat analysis. Adverse events were summarised by treatment.

Findings: The modified intention-to-treat analysis consisted of 630 patients (efavirenz 400=321; efavirenz 600=309). 32% were women; 37% were African, 33% were Asian, and 30% were white. The mean baseline CD4 cell count was 273 cells per µL (SD 99) and median plasma HIV-RNA was 4.75 log10 copies per mL (IQR 0.88). The proportion of participants with a viral load below 200 copies per mL at week 48 was 94.1% for efavirenz 400 mg and 92.2% for 600 mg (difference 1.85%, 95% CI -2.1 to 5.79). CD4 T-cell counts at week 48 were significantly higher for the 400 mg group than for the 600 mg group (mean difference 25 cells per µL, 95% CI 6-44; p=0.01). We recorded no difference in grade or number of patients reporting adverse events (efavirenz 400=89.1%, efavirenz 600=88.4%; difference 0.75%, 95% CI -4.19 to 5.69; p=0.77). Study drug-related adverse events were significantly more frequent in the 600 mg group than in the 400 mg group (146% [47] vs 118 [37]), difference -10.5%, 95% CI -18.2 to -2.8; p=0.01) and significantly fewer patients with these events stopped treatment (400 mg=6 [2%], 600 mg=18 [6%], difference -3.96%, 95% CI -6.96 to -0.95; p=0.01).

Interpretation: Our findings suggest that a reduced dose of 400 mg efavirenz is non-inferior to the standard dose of 600 mg, when combined with tenofovir and emtricitabine during 48 weeks in ART-naive adults with HIV-1 infection. Adverse events related to the study drug were more frequent with 600 mg efavirenz than with 400 mg. Lower dose efavirenz should be recommended as part of routine care.

Abstract access

Editor’s notes: Nearly 10 million people in low- and middle-income countries were receiving antiretroviral therapy (ART) by the end of 2012, with plans to expand coverage to 15 million by 2015. Several challenges must be overcome if this target is to be achieved. One of the most pertinent of these is how to fund this expansion in the current economic climate. Significant progress has already been made in reducing the cost of first-line drugs. The authors of this paper propose an alternative approach to lowering drug costs, namely dose reduction.

Evidence supporting the 600mg dose of efavirenz used in clinical practice is weak, with no difference found in the proportion of patients achieving viral suppression in the original dose finding trials of 200mg, 400mg and 600mg (unpublished). This trial in ART-naive individuals found that 400mg was non-inferior to 600mg of efavirenz in terms of viral suppression over 48 weeks of follow-up. Findings were similar when stratified by ethnic group (African, Asian, other) and body mass index, both factors which influence drug concentrations. Furthermore, fewer patients on 400mg reported adverse events which were related to efavirenz, and fewer patients with drug-related side effects on this dose stopped efavirenz. These promising results support a dose reduction strategy. However, longer term outcomes need to be evaluated and efficacy studies in patients with tuberculosis are needed before the 400mg dose is recommended for use in routine clinical practice. Certainly, if drug companies agree to manufacture this dose at scale, preferably in fixed-dose combination tablets, cost-savings could be considerable.  

Africa, Asia, Europe, Latin America
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