Beyond first-line HIV treatment regimens

Kumarasamy, Nagalingeswaran; Krishnan, Sheela

doi:10.1097/coh.0000000000000004

Cited by 16 publications

(13 citation statements)

References 27 publications

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“…Although, there have been substantial improvements to the care of HIV-positive patients in the Asia-Pacific region, disparities in income and care infrastructures are important factors that influence a country’s ability to offer optimal care to HIV-positive patients, which impacts long-term outcomes and risks of drug resistance and mortality [23, 24]. Therefore, there is a distinct need to monitor and document the survival trends of HIV-positive patients in the Asia-Pacific.…”

Section: Introductionmentioning

confidence: 99%

Improved Survival in HIV Treatment Programmes in Asia

Mata¹,

Kumarasamy

Khol

et al. 2015

Antiviral Therapy

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Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (p<0.001). Factors associated with higher mortality risk included initiating ART in earlier time periods, older age, male sex, injecting drug use as HIV exposure and lower pre-ART CD4 count. Concurrent with improved survival was increased tenofovir use, ART initiation at higher CD4 counts, and greater monitoring of CD4 and HIV viral load. Conclusions Our results suggest that HIV-positive patients from Asia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time.

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Section: Introductionmentioning

confidence: 99%

Improved Survival in HIV Treatment Programmes in Asia

Mata¹,

Kumarasamy

Khol

et al. 2015

Antiviral Therapy

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“…These therapies efficiently suppress the spread of HIV in patients; however, the emergence of drugresistant viruses is a continuous challenge to the effectiveness of these interventions. In addition, these antiretroviral drugs have important side effects that limit their use (2)(3)(4). Therefore, the development of new and safer anti-HIV compounds is a critical need (1,5,6).…”

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confidence: 99%

Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

Martinez

Castro

Seong

et al. 2016

Antimicrob Agents Chemother

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Three compounds (1, 2, and 3) previously reported to inhibit HIV-1 replication and/or in vitro activity of reverse transcriptase were studied, but only fullerene derivatives 1 and 2 showed strong antiviral activity on the replication of HIV-1 in human CD4 ؉ T cells. However, these compounds did not inhibit infection by single-round infection vesicular stomatitis virus glycoprotein G (VSV-G)-pseudotyped viruses, indicating no effect on the early steps of the viral life cycle. In contrast, analysis of single-round infection VSV-G-pseudotyped HIV-1 produced in the presence of compound 1 or 2 showed a complete lack of infectivity in human CD4؉ T cells, suggesting that the late stages of the HIV-1 life cycle were affected. Quantification of virion-associated viral RNA and p24 indicates that RNA packaging and viral production were unremarkable in these viruses. However, Gag and Gag-Pol processing was affected, as evidenced by immunoblot analysis with an anti-p24 antibody and the measurement of virion-associated reverse transcriptase activity, ratifying the effect of the fullerene derivatives on virion maturation of the HIV-1 life cycle. Surprisingly, fullerenes 1 and 2 did not inhibit HIV-1 protease in an in vitro assay at the doses that potently blocked viral infectivity, suggesting a protease-independent mechanism of action. Highlighting the potential therapeutic relevance of fullerene derivatives, these compounds block infection by HIV-1 resistant to protease and maturation inhibitors.

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“…In developed countries, there are ample resources to provide optimal patient care, including HIV viral load monitoring, drug resistance testing and alternate ARV drugs, so ART regimens after first treatment failure can be accommodated. In resource-limited settings (RLS), patients have limited options due to drug affordability, minimal laboratory monitoring and ARV drug supply (Duda et al, 2014; Hirsch et al, 2008; Kumarasamy & Krishnan, 2013; Long, Fox, Sanne, & Rosen, 2010). Hence, the rate of switching from the first-line ART to the second ART is lower in resource-limited settings compared to developed countries (Group et al, 2009; Pujades-Rodriguez et al, 2010; Renaud-Thery et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Over half the patients in 2013 did not have a current HIV viral load. Many ART programmes in RLS have minimal HIV viral load monitoring for patients due to inadequate laboratory equipment and high cost (Boyer et al, 2013; Kumarasamy & Krishnan, 2013). In these settings, HIV viral load testing is targeted rather than routine to confirm treatment failure, but potential delays in treatment switching can increase the risk of disease progression, drug resistance and HIV transmission (Arnedo et al, 2012; Kanapathipillai et al, 2011; Nettles et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Growing challenges for HIV programmes in Asia: clinic population trends, 2003–2013

Mata¹,

Kumarasamy

et al. 2017

AIDS Care

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The scale-up of antiretroviral therapy (ART) has led to a substantial change in the clinical population of HIV-positive patients receiving care. We describe the temporal trends in the demographic and clinical characteristics of HIV-positive patients initiating ART in 2003–13 within an Asian regional cohort. All HIV-positive adult patients that initiated ART between 2003 and 2013 were included. We summarized ART regimen use, age, CD4 cell count, HIV viral load, and HIV-related laboratory monitoring rates during follow-up by calendar year. A total of 16 962 patients were included in the analysis. Patients in active follow-up increased from 695 patients at four sites in 2003 to 11,137 patients at eight sites in 2013. The proportion of patients receiving their second or third ART regimen increased over time (5% in 2003 to 29% in 2013) along with patients aged ≥50 years (8% in 2003 to 18% in 2013). Concurrently, CD4 monitoring has remained stable in recent years, whereas HIV viral load monitoring, although varied among the sites, is increasing. There have been substantial changes in the clinical and demographic characteristics of HIV-positive patients receiving ART in Asia. HIV programmes will need to anticipate the clinical care needs for their aging populations, expanded viral load monitoring, and, the eventual increase in second and third ART regimens that will lead to higher costs and more complex drug procurement needs.

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Beyond first-line HIV treatment regimens

Cited by 16 publications

References 27 publications

Improved Survival in HIV Treatment Programmes in Asia

Improved Survival in HIV Treatment Programmes in Asia

Fullerene Derivatives Strongly Inhibit HIV-1 Replication by Affecting Virus Maturation without Impairing Protease Activity

Growing challenges for HIV programmes in Asia: clinic population trends, 2003–2013

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