Iskandar Azwa

Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: results from the TREAT Asia HIV observational database.

Background:Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources, it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. Methods:HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. Results:There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007–2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Conclusions:Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.

Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study

BACKGROUNDnLipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir.nnnMETHODSnOf the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122.nnnFINDINGSnBetween Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10).nnnINTERPRETATIONnOur findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen.nnnFUNDINGnThe Kirby Institute and the Australian National Health and Medical Research Council.

Willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia: findings from a qualitative study.

Background: Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre‐exposure prophylaxis (PrEP), an antiretroviral ‐based medication taken by HIV‐negative men to prevent sero‐conversion. In order for such promising findings to be translated in real‐world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake.

Willingness to use pre-exposure prophylaxis for HIV prevention among men who have sex with men in Malaysia : Findings from an online survey

Objective We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia. Methods An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants’ demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP. Results Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals. Conclusions Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.

Significant health impact of accelerated aging in young HIV-infected individuals on antiretroviral therapy in Malaysia

Background: Aging among HIV-infected individuals on antiretroviral therapy (ART) is a significant clinical challenge; however, studies assessing multidimensional aspects of aging are lacking. We characterized 10 geriatric conditions encompassing multiple functional domains, its health impact and associated risk factors in HIV-infected and age-matched uninfected controls. Methods: HIV-infected individuals were recruited from the outpatient clinic in University Malaya Medical Centre, Malaysia and controls from the community. All participants were aged at least 25 years of age with no acute illness, and HIV-infected individuals were on stable ART. Geriatric conditions were assessed and the burden scored as a composite of geriatric conditions present in an individual (total scoreu200a=u200a10). Multivariate regression analysis was performed to determine the risk factors and health impact associated with the burden of geriatric conditions. Results: We analyzed data from 336 HIV-infected individuals (total HIV+), of whom 172 were matched for age, sex, and ethnicity with 172 HIV-uninfected controls (matched subset). In the total HIV-positive cohort, median (interquartile range) age was 44 (38–51) years and CD4+ T-cell count was 562 (398–737) cells/&mgr;l. The burden of geriatric conditions was significantly higher in the HIV-infected group compared with controls (Pu200a<u200a0.001). With an increasing geriatric condition burden, quality-of-life scores were 2.2-times poorer, healthcare use five times greater, and mortality risk scores four times higher in the HIV-infected group compared with matched controls. Both sociobehavioural and HIV-related clinical factors were independently associated with an increasing burden of geriatric condition in HIV. Conclusions: A high burden of geriatric conditions with significant impact on health outcomes, including mortality risk scores are observed among HIV-infected individuals on ART in a resource-limited setting.

HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution

Background Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants. Method In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression. Results A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation. Conclusion Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.

Human papillomavirus (HPV)‐associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6‐specific interferon (IFN)‐γ enzyme‐linked immunospot (ELISPOT) T‐cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution.

The occurrence of Simpson's paradox if site-level effect was ignored in the TREAT Asia HIV Observational Database

OBJECTIVESnIn multisite human immunodeficiency virus (HIV) observational cohorts, clustering of observations often occurs within sites. Ignoring clustering may lead to Simpsons paradox (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox regression models.nnnSTUDY DESIGN AND SETTINGnSurvival time from combination antiretroviral therapy (cART) initiation was analyzed using four Cox models: (1) no site adjustment; (2) site as a fixed effect; (3) stratification through site; and (4) shared frailty on site.nnnRESULTSnA total of 6,454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (1) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HRxa0=xa00.68 vs. 0.61). Models (2)-(4) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from model (1). The effects of other significant covariates on survival were similar across four models.nnnCONCLUSIONSnIgnoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.

Is the risk of tenofovir-induced nephrotoxicity similar in treatment-naïve compared to treatment-experienced patients?

Tenofovir disoproxil fumarate (TDF) is the recommended first‐line nucleoside reverse transcriptase inhibitor (NRTI) in the management of human immunodeficiency virus (HIV); however, its use is associated with nephrotoxicity.

Early suboptimal ART adherence was associated with missed clinical visits in HIV-infected patients in Asia

ABSTRACT Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence <95% were more likely to have a missed visit compared to those with adherence ≥95% (ORu2009=u20092.55, 95% CI(1.81–3.61)). Other factors associated with having a missed visit were homosexual (ORu2009=u20091.45, 95%CI(1.27–1.66)) and other modes of HIV exposure (ORu2009=u20091.48, 95%CI(1.27–1.74)) compared to heterosexual exposure; using PI-based (ORu2009=u20091.33, 95%CI(1.15–1.53) and other ART combinations (ORu2009=u20091.79, 95%CI(1.39–2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (ORu2009=u20091.27, 95%CI(1.06–1.52)). Patients aged >30 years (31–40 years ORu2009=u20090.81, 95%CI(0.73–0.89); 41–50 years ORu2009=u20090.73, 95%CI(0.64–0.83); and >50 years ORu2009=u20090.77, 95%CI(0.64–0.93)); female sex (ORu2009=u20090.81, 95%CI(0.72–0.90)); and being from upper middle (ORu2009=u20090.78, 95%CI(0.70–0.80)) or high-income countries (ORu2009=u20090.42, 95%CI(0.35–0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.