Publications by authors named "Sanjay Pujari"

58 Publications

Weight changes, metabolic syndrome and all-cause mortality among Asian adults living with HIV.

HIV Med 2021 Nov 23. Epub 2021 Nov 23.

HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Objectives: We investigated weight changes following antiretroviral therapy (ART) initiation, the development of metabolic syndrome (MetS) and its association with all-cause mortality among Asian adults living with HIV.

Methods: Participants enrolled in a regional Asian HIV-infected cohort with weight and height measurements at ART initiation were eligible for inclusion in the analysis. Factors associated with weight changes and incident MetS (according to the International Diabetic Federation (IDF) definition) were analysed using linear mixed models and Cox regression, respectively. Competing-risk regression models were used to investigate the association of MetS with all-cause mortality.

Results: Among 4931 people living with HIV (PLWH), 66% were male. At ART initiation, the median age was 34 [interquartile range (IQR) 29-41] years, and the median (IQR) weight and body mass index (BMI) were 55 (48-63) kg and 20.5 (18.4-22.9) kg/m , respectively. At 1, 2 and 3 years of ART, overall mean (± standard deviation) weight gain was 2.2 (±5.3), 3.0 (±6.2) and 3.7 (±6.5) kg, respectively. Participants with baseline CD4 count ≤ 200 cells/µL [weight difference (diff) = 2.2 kg; 95% confidence interval (CI) 1.9-2.5 kg] and baseline HIV RNA ≥ 100 000 HIV-1 RNA copies/mL (diff = 0.6 kg; 95% CI 0.2-1.0 kg), and those starting with integrase strand transfer inhibitor (INSTI)-based ART (diff = 2.1 kg; 95% CI 0.7-3.5 kg vs. nonnucleoside reverse transcriptase inhibitors) had greater weight gain. After exclusion of those with abnormal baseline levels of MetS components, 295/3503 had incident MetS [1.18 (95% CI 1.05-1.32)/100 person-years (PY)]. The mortality rate was 0.7 (95% CI 0.6-0.8)/100 PY. MetS was not significantly associated with all-cause mortality in the adjusted model (P = 0.236).

Conclusions: Weight gain after ART initiation was significantly higher among those initiating ART with lower CD4 count, higher HIV RNA and an INSTI-based regimen after controlling for baseline BMI. Greater efforts to identify and manage MetS among PLWH are needed.
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http://dx.doi.org/10.1111/hiv.13211DOI Listing
November 2021

Virological outcome and frequency of low-level viremia in patients receiving generic dolutegravir-containing regimen at a large tertiary care clinic in Western India.

Indian J Sex Transm Dis AIDS 2021 Jan-Jun;42(1):31-37. Epub 2021 May 3.

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.

Background: Dolutegravir (DTG) is widely used for the management of naïve and treatment-experienced HIV-infected patients. Low-level viremia (LLV) is common in patients receiving nonnucleoside reverse transcriptase inhibitor- and protease inhibitor-containing regimens. However, the incidence of LLV associated with DTG-containing regimen is not well known.

Objective: The objective of this study was to assess the virological response associated with DTG-containing regimens and explored frequencies of LLV and risk factors for the same.

Methods: We performed a retrospective cohort study of HIV-infected patients receiving generic DTG-containing regimen from February 2017 to July 2019. All adult patients (≥18 years), who completed at least the first follow-up after initiating treatment, were included in this study. LLV was defined as plasma viral load between 20 and 200 copies/ml.

Results: A total of 597 patients started DTG-containing regimen during the study period, of which 522 patients met the inclusion criteria. The study patients were categorized into five groups: naïve ( = 86), first-line failure ( = 32), second-line failure ( = 53), switch ( = 325), and HIV-2 ( = 26). Complete virological suppression at 6, 12, and 18 months was achieved in 78.5%, 81.1%, and 70.9% of the patients, respectively. Furthermore, 17.9%, 12.9%, and 23.3% of the patients had LLV at 6, 12, and 18 months, respectively. Persistent LLV was found in 2.9% of the patients. Overall, DTG was well tolerated and was discontinued in only three patients due to neuropsychiatric side effects.

Conclusion: DTG is well tolerated and effective in suppressing HIV across all antiretroviral treatment categories. The rate of persistent LLV is low in DTG-containing therapy.
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http://dx.doi.org/10.4103/ijstd.IJSTD_34_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579596PMC
May 2021

Long-coronavirus disease among people living with HIV in western India: An observational study.

Immun Inflamm Dis 2021 09 2;9(3):1037-1043. Epub 2021 Jun 2.

Institute of Infectious Diseases, Pune, India.

Background: Long-COVID is emerging as a significant problem among individuals who recovered from COVID-19. Scant information is available on the prevalence, characteristics, and risk factors for long-COVID among people living with HIV (PLHIV).

Setting: A tertiary level, private, HIV clinic in western India.

Methods: A prospective, observational study was conducted to assess the prevalence of long-COVID among PLHIV. Long-COVID was defined as the presence of at least one symptom after 30 days of illness onset. A questionnaire for assessing general, cardiorespiratory, neuro-psychiatric, and gastro-intestinal symptoms was used to screen individuals with history of confirmed COVID-19. Data on demographics, HIV-related variables, comorbidities, and severity of COVID-19 were abstracted from electronic medical records. Univariate and multivariate logistic regression were used to identify risk factors for long-COVID.

Results: Ninety-four PLHIV were screened for long-COVID. Median (interquartile range [IQR]) age was 51 (47-56) years and 73.4% were males. The majority (76.6%) had a history of asymptomatic-mild COVID-19 illness. The prevalence of long-COVID was 43.6% (95% confidence interval [CI], 33.4-54.2). Moderate-severe COVID-19 illness was significantly associated with long-COVID (adjusted odds ratio, 4.7; 95% CI, 1.4-17.9; p = .016). Among individuals with long-COVID, cough (22.3%) and fatigue (19.1%) were the commonest symptoms. The median (IQR) duration for resolution of symptoms was 15 (7-30) days. Ten individuals (10.6%) had persistent symptoms at a median of 109 days since the onset of COVID-19.

Conclusion: Long-COVID is common among PLHIV with moderate-severe acute COVID-19 illness. There is a need for integration of long-COVID diagnosis and care services within antiretroviral therapy clinics for PLHIV with COVID-19.
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http://dx.doi.org/10.1002/iid3.467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239760PMC
September 2021

Short Communication: Coronavirus Disease 19 Among People Living with HIV in Western India: An Observational Cohort Study.

AIDS Res Hum Retroviruses 2021 08 31;37(8):620-623. Epub 2021 May 31.

Institute of Infectious Diseases, Pune, India.

A retrospective cohort study was conducted to assess clinical characteristics and outcomes of coronavirus disease-19 (COVID-19) among people living with HIV (PLHIV) in western India. Out of 86 PLHIV with COVID-19 illness, 19.7% had severe/critical illness and 6 (6.9%) individuals died. Median (interquartile range) age was 51 (47-56) years and 77.6% were male. Eighty-five PLHIV were on antiretroviral treatment with 98% having a viral load <200 copies/mL. Hypertension (HTN) (38.3%) and diabetes mellitus (17.4%) were commonest comorbidities. Fifty-eight percent PLHIV were hospitalized while 6.9% individuals needed intensive care. Presence of medical comorbidity was significantly associated with severe/critical COVID-19, whereas HTN was significantly associated with mortality. Recovery from COVID-19 was documented in 93% PLHIV. In conclusion, PLHIV in western India have similar COVID-19 clinical outcomes as compared with those reported historically among general population. Presence of medical comorbidities rather than HIV-related disease characteristics is associated with severe COVID-19 illness.
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http://dx.doi.org/10.1089/AID.2021.0004DOI Listing
August 2021

Treatment modification after second-line failure among people living with HIV in the Asia-Pacific.

Antivir Ther 2020 ;25(7):377-387

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background: The World Health Organization recommends continuation with the failing second-line regimen if third-line option is not available. We investigated treatment outcomes among people living with HIV in Asia who continued with failing second-line regimens compared with those who had treatment modifications after failure.

Methods: Treatment modification was defined as a change of two antiretrovirals, a drug class change or treatment interruption (TI), all for >14 days. We assessed factors associated with CD4 changes and undetectable viral load (UVL <1,000 copies/ml) at 1 year after second-line failure using linear and logistic regression, respectively. Survival time was analysed using competing risk regression.

Results: Of the 328 patients who failed second-line ART in our cohorts, 208 (63%) had a subsequent treatment modification. Compared with those who continued the failing regimen, the average CD4 cell increase was higher in patients who had a modification without TI (difference =77.5, 95% CI 35.3, 119.7) while no difference was observed among those with TI (difference =-5.3, 95% CI -67.3, 56.8). Compared with those who continued the failing regimen, the odds of achieving UVL was lower in patients with TI (OR=0.18, 95% CI 0.06, 0.60) and similar among those who had a modification without TI (OR=1.97, 95% CI 0.95, 4.10), with proportions of UVL 60%, 22% and 75%, respectively. Survival time was not affected by treatment modifications.

Conclusions: CD4 cell improvements were observed in those who had treatment modification without TI compared with those on the failing regimen. When no other options are available, maintaining the same failing ART combination provided better VL control than interrupting treatment.
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http://dx.doi.org/10.3851/IMP3388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275121PMC
January 2020

An expanded HIV care cascade: ART uptake, viral load suppression and comorbidity monitoring among adults living with HIV in Asia.

Antivir Ther 2020 ;25(5):275-285

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background: Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (CKD) and diabetes monitoring.

Methods: We included patients ≥18 years in care at ten clinical sites in eight Asian countries. Proportions of patients on antiretroviral therapy (ART), with annual viral load, and with viral load suppression (VLS; <1,000 copies/ml) were estimated by year for 2011-2016, stratified by country income level (lower-middle income [LMIC] and high-income countries [HIC]). Among those on ART in 2016 we evaluated factors associated with annual CKD and diabetes monitoring.

Results: Among 31,346 patients (67% male), the proportions of patients on ART (median ART initiation year 2011, IQR 2007-2013), with annual viral load and VLS had substantially increased by 2016 (to 94%, 42% and 92%, respectively, in LMIC and 95%, 97% and 93%, respectively, in HIC) with the larger increases over time seen in LMIC. Among those on ART in 2016, monitoring proportions in LMIC were 53% for CKD and 26% for diabetes compared with 83% and 59%, respectively, in HIC. Overall, a decreased odds of monitoring was observed for male gender, heterosexual HIV exposure, no viral load and LMIC. Diabetes monitoring was also decreased in those with viral failure.

Conclusions: Our findings highlight suboptimal monitoring of viral load, CKD and diabetes in PLHIV in Asia. There is a need for affordable and scalable monitoring options to improve the joint care for HIV and non-communicable diseases.
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http://dx.doi.org/10.3851/IMP3379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272912PMC
October 2021

Validation of the D: A: D Chronic Kidney Disease Risk Score Model Among People Living With HIV in the Asia-Pacific.

J Acquir Immune Defic Syndr 2020 12;85(4):489-497

HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Background: We validated the Data collection on Adverse events of anti-HIV Drugs (D:A:D) full-risk and short-risk score models for chronic kidney disease (CKD) in the Asian HIV cohorts.

Settings: A validation study among people living with HIV (PLHIV) aged ≥18 years among the cohorts in the Asia-Pacific region.

Methods: PLHIV with a baseline estimated glomerular filtration rate > 60 mL/min/1.73 m were included for validation of the D:A:D CKD full version and short version without cardiovascular risk factors. Those with <3 estimated glomerular filtration rate measurements from baseline or previous exposure to potentially nephrotoxic antiretrovirals were excluded. Kaplan-Meier methods were used to estimate the probability of CKD development. The area under the receiver operating characteristics was also used to validate the risk score.

Results: We included 5701 participants in full model {median 8.1 [interquartile range (IQR) 4.8-10.9] years follow-up} and 9791 in short model validation [median 4.9 (IQR 2.5-7.3) years follow-up]. The crude incidence rate of CKD was 8.1 [95% confidence interval (CI): 7.3 to 8.9] per 1000 person-years in the full model cohort and 10.5 (95% CI: 9.6 to 11.4) per 1000 person-years in the short model cohort. The progression rates for CKD at 10 years in the full model cohort were 2.7%, 8.9%, and 26.1% for low-risk, medium-risk, and high-risk groups, and 3.5%, 11.7%, and 32.4% in the short model cohort. The area under the receiver operating characteristics for the full-risk and short-risk score was 0.81 (95% CI: 0.79 to 0.83) and 0.83 (95% CI: 0.81 to 0.85), respectively.

Conclusion: The D:A:D CKD full-risk and short-risk score performed well in predicting CKD events among Asian PLHIV. These risk prediction models may be useful to assist clinicians in identifying individuals at high risk of developing CKD.
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http://dx.doi.org/10.1097/QAI.0000000000002464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018533PMC
December 2020

Survival after long-term ART exposure: findings from an Asian patient population retained in care beyond 5 years on ART.

Antivir Ther 2020 ;25(3):131-142

The Kirby Institute, UNSW Sydney, Kensington, NSW, Australia.

Background: This study investigated survival in people living with HIV being followed-up from 5 and 10 years after antiretroviral therapy (ART) initiation in a multi-country Asian cohort.

Methods: We included patients in follow-up >5 years after ART initiation. Factors associated with mortality beyond 5 and 10 years on ART were analysed using competing risk regression with time-updated variables.

Results: Of 13,495 patients retained after 5 years on ART, 279 subsequently died (0.56/100 person-years). Increased mortality was associated with age >50 years (sub-hazard ratio [sHR] 2.24, 95% CI 1.58, 3.15, compared with ≤40 years), HIV exposure through injecting drug use (sHR 2.17, 95% CI 1.32, 3.56), HIV viral load ≥1,000 copies/ml: sHR 1.52, 95% CI 1.05, 2.21, compared with <400), regimen (second-line regimen: sHR 2.11, 95% CI 1.52, 2.94, and third-line regimen: sHR 2.82, 95% CI 2.00, 3.98, compared with first-line regimen), HBV coinfection (sHR 2.23, 95% CI 1.49, 3.33), fasting plasma glucose ≥126 mg/dl (sHR 1.98, 95% CI 1.22, 3.21, compared with <100 mg/dl) and estimated glomerular filtration rate <60 ml/min/1.73 m (sHR 2.57, 95% CI 1.56, 4.22). Decreased mortality was associated with transmission through male-to-male sexual contact (sHR 0.44, 95% CI 0.22, 0.88, compared with heterosexual transmission) and higher CD4 T-cell count (200-349 cells/µl: sHR 0.27, 95% CI 0.20, 0.38, 350-499 cells/µl: sHR 0.10, 95% CI 0.07, 0.16 and ≥500 cells/µl: sHR 0.09, 95% CI 0.06, 0.13, compared with <200 cells/µl). Results after 10 years were similar, but most associations were weaker due to limited power.

Conclusions: Next to preventing ART failure, HIV programmes should carefully monitor and treat comorbidities, including hepatitis, kidney disease and diabetes, to optimize survival after long-term ART exposure.
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http://dx.doi.org/10.3851/IMP3358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641962PMC
October 2021

Effectiveness of dolutegravir-based antiretroviral treatment for HIV-2 infection: retrospective observational study from Western India.

J Antimicrob Chemother 2020 07;75(7):1950-1954

Institute of Infectious Diseases, Pune, India.

Background: Data on the use of dolutegravir for treatment of HIV-2 infection are limited.

Objectives: To assess the effectiveness of dolutegravir in people living with HIV-2 (PLHIV-2).

Methods: A retrospective chart review was performed in two clinics in Western India. PLHIV-2 initiated on dolutegravir-based regimens were included. Response to treatment in both treatment-naive (TN) and treatment-experienced (TE; substitution and not in the context of failure) was assessed by CD4 counts and HIV-2 viral load (VL) in a proportion of individuals. The primary objective was to assess immunological effectiveness (absence of a drop in absolute CD4 counts by more than 30% of baseline). Change in absolute CD4 counts was assessed by fitting a mixed-effects model.

Results: Sixty-two PLHIV-2 treated with dolutegravir were included. The immunological effectiveness rates (95% CI) were 91.9% (82.4%-96.5%), 92% (81.1%-96.8%) and 91.6% (64.6%-98.5%) amongst all, TE and TN individuals, respectively. Median change in absolute CD4 counts at 6, 12 and 18 months were +29 cells/mm3, +101 cells/mm3 and +72 cells/mm3, respectively. The virological effectiveness rates (HIV-2 VL <100 copies/mL) (95% CI) for all, TE and TN individuals were 88.8% (74.6%-95%), 89.6% (73.6%-96.4%) and 85.7% (48.6%-97.4%), respectively. Three clinical events were documented: spinal tuberculosis, relapsed non-Hodgkin's lymphoma and herpes simplex virus retinitis. One individual reported self-limiting somnolence.

Conclusions: Dolutegravir was well tolerated and associated with immunological, virological and clinical effectiveness in both TN and TE PLHIV-2 in a large cohort from Western India. Dolutegravir-based ART is an excellent option for treatment of individuals with HIV-2 infection.
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http://dx.doi.org/10.1093/jac/dkaa112DOI Listing
July 2020

High prevalence of multi drug resistant tuberculosis in people living with HIV in Western India.

BMC Infect Dis 2019 May 8;19(1):391. Epub 2019 May 8.

Institute of Infectious Diseases, Pune, India.

Background: Most studies assessing drug resistant tuberculosis (DRTB) in human immunodeficiency virus (HIV) co-infected patients in India have used conventional culture- based systems to diagnose DRTB that have a longer turnaround time leading to risk of amplification of resistance to an empirical regimen. We determined the prevalence of DRTB amongst people living with HIV (PLHIV) using the line probe assay and determined risk factors associated with the presence of multi drug resistant tuberculosis (MDRTB).

Methods: A Cross-sectional study was undertaken at Poona Hospital and Research Center (PHRC) and the Institute of Infectious Diseases, two tertiary level private care centers in Pune, India. Consenting PLHIV with confirmed Pulmonary TB (PTB) and/or extra-pulmonary TB (EPTB) diagnosed based on detection of Mycobacterium TB by line probe assay (Geno Type MTBDRplus version 2) on clinical specimens were included. Those with documented past history of DRTB were excluded. Resistance against anti-TB drugs was determined by the same assay. The prevalence of any form of drug resistant TB (DRTB), MDRTB, Rifampicin resistant TB (RRTB) and Isoniazid (INH) mono-resistant TB were determined as the proportion of these amongst all included PLHIV-TB. A multivariate analysis was conducted to determine risk factors that were statistically associated with MDRTB, DRTB, RRTB and INH mono-resistant TB.

Results: Two hundred PLHIV were recruited. The prevalence (95% CI) of MDRTB, INH mono- resistance and RR resistance was 12.5% (7.9-17.1%), 9% (6.9-11.2%) and 2.5% (1.4-3.6%), respectively. The prevalence (95% CI) of MDRTB among new and relapsed patients was 8.8% (6.5-11.1%) and 23.1% (17.2-28.9%), respectively. Tuberculosis relapse was the only factor significantly associated with MDRTB, DRTB and INH mono-resistant TB.

Conclusion: We document a high prevalence of drug resistance to anti-TB drugs including MDRTB among PLHIV in our setting using Geno Type MTBDRplus directly on clinical specimens. This validates the WHO recommendation of performing routine rapid molecular resistance testing prior to initiating anti-TB treatment among all PLHIV with presumptive TB. Using rapid molecular testing especially Geno Type MTBDRplus (that detects resistance to INH and Rifampicin simultaneously) reduces the turn-around time helping in optimizing treatment.
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http://dx.doi.org/10.1186/s12879-019-4042-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507020PMC
May 2019

Cardiovascular disease incidence projections in the TREAT Asia HIV Observational Database (TAHOD).

Antivir Ther 2019 ;24(4):271-279

The Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.

Background: We aimed to project the 10-year future incidence of cardiovascular disease (CVD) and model several intervention scenarios based on a multi-site Asian HIV-positive cohort.

Methods: Analyses were based on patients recruited to the TREAT Asia HIV Observational Database (TAHOD), consisting of 21 sites in 12 countries. Patients on triple antiretroviral therapy (ART) were included if they were alive, without previous CVD, and had data on CVD risk factors. Annual new CVD events for 2019-2028 were estimated with the D:A:D equation, accounting for age- and sex-adjusted mortality. Modelled intervention scenarios were treatment of high total cholesterol, low high-density lipoprotein cholesterol (HDL) or high blood pressure, abacavir or lopinavir substitution, and smoking cessation.

Results: Of 3,703 included patients, 69% were male, median age was 46 (IQR 40-53) years and median time since ART initiation was 9.8 years (IQR 7.5-14.1). Cohort incidence rates of CVD were projected to increase from 730 per 100,000 person-years (pys) in 2019 to 1,432 per 100,000 pys in 2028. In the modelled intervention scenarios, most events can be avoided by smoking cessation, abacavir substitution, lopinavir substitution, decreasing total cholesterol, treating high blood pressure and increasing HDL.

Conclusions: Our projections suggest a doubling of CVD incidence rates in Asian HIV-positive adults in our cohort. An increase in CVD can be expected in any ageing population, however, according to our models, this can be close to averted by interventions. Thus, there is an urgent need for risk screening and integration of HIV and CVD programmes to reduce the future CVD burden.
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http://dx.doi.org/10.3851/IMP3298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728217PMC
June 2020

The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV.

J Int AIDS Soc 2019 02;22(2):e25228

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Introduction: Multiple comorbidities among HIV-positive individuals may increase the potential for polypharmacy causing drug-to-drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age-associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age-associated comorbidities on therapeutic outcomes of cART in HIV-positive adults in Asian countries.

Methods: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in-line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure.

Results: The incidence of virologic failure was 7.72/100 person-years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age-related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person-years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities.

Conclusions: In our Asia regional cohort, age-associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.
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http://dx.doi.org/10.1002/jia2.25228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389354PMC
February 2019

Diabetes mellitus burden among people living with HIV from the Asia-Pacific region.

J Int AIDS Soc 2019 01;22(1):e25236

HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand.

Introduction: Comorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new-onset DM among PLHIV in Asian settings.

Methods: PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two-hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.

Results And Discussion: Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow-up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person-years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow-up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p < 0.001) compared to <2010, older age (41 to 50 years: HR = 2.46, 95% CI 1.39 to 4.36, p  = 0.002; and >50 years: HR = 4.19, 95% CI 2.12 to 8.28, p < 0.001) compared to <30 years, body mass index (BMI) >30 kg/m (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m , and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).

Conclusions: Type 2 DM in HIV-infected Asians was associated with later years of follow-up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non-communicable diseases including DM as PLHIV age.
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http://dx.doi.org/10.1002/jia2.25236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351701PMC
January 2019

Effect of Macrolide Prophylactic Therapy on AIDS-Defining Conditions and HIV-Associated Mortality.

J Acquir Immune Defic Syndr 2019 04;80(4):436-443

Research Institute for Tropical Medicine, Muntinlupa, Philippines.

Background: Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.

Methods: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation.

Results: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation.

Conclusions: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.
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http://dx.doi.org/10.1097/QAI.0000000000001933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391185PMC
April 2019

Brief Report: Malignancies in Adults Living With HIV in Asia.

J Acquir Immune Defic Syndr 2019 03;80(3):301-307

Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Hematological malignancies have continued to be highly prevalent among people living with HIV (PLHIV). This study assessed the occurrence of, risk factors for, and outcomes of hematological and nonhematological malignancies in PLHIV in Asia.

Methods: Incidence of malignancy after cohort enrollment was evaluated. Factors associated with development of hematological and nonhematological malignancy were analyzed using competing risk regression and survival time using Kaplan-Meier.

Results: Of 7455 patients, 107 patients (1%) developed a malignancy: 34 (0.5%) hematological [0.08 per 100 person-years (/100PY)] and 73 (1%) nonhematological (0.17/100PY). Of the hematological malignancies, non-Hodgkin lymphoma was predominant (n = 26, 76%): immunoblastic (n = 6, 18%), Burkitt (n = 5, 15%), diffuse large B-cell (n = 5, 15%), and unspecified (n = 10, 30%). Others include central nervous system lymphoma (n = 7, 21%) and myelodysplastic syndrome (n = 1, 3%). Nonhematological malignancies were mostly Kaposi sarcoma (n = 12, 16%) and cervical cancer (n = 10, 14%). Risk factors for hematological malignancy included age >50 vs. ≤30 years [subhazard ratio (SHR) = 6.48, 95% confidence interval (CI): 1.79 to 23.43] and being from a high-income vs. a lower-middle-income country (SHR = 3.97, 95% CI: 1.45 to 10.84). Risk was reduced with CD4 351-500 cells/µL (SHR = 0.20, 95% CI: 0.05 to 0.74) and CD4 >500 cells/µL (SHR = 0.14, 95% CI: 0.04 to 0.78), compared to CD4 ≤200 cells/µL. Similar risk factors were seen for nonhematological malignancy, with prior AIDS diagnosis showing a weak association. Patients diagnosed with a hematological malignancy had shorter survival time compared to patients diagnosed with a nonhematological malignancy.

Conclusions: Nonhematological malignancies were common but non-Hodgkin lymphoma was more predominant in our cohort. PLHIV from high-income countries were more likely to be diagnosed, indicating a potential underdiagnosis of cancer in low-income settings.
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http://dx.doi.org/10.1097/QAI.0000000000001918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375805PMC
March 2019

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

Pharmacoepidemiol Drug Saf 2018 11 24;27(11):1209-1216. Epub 2018 Sep 24.

Institute of Infectious Diseases, Pune, India.

Purpose: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia.

Methods: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).

Results: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.

Conclusions: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.
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http://dx.doi.org/10.1002/pds.4657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6218305PMC
November 2018

AIDS Cholangiopathy Secondary to Cytomegalovirus as Possible Unmasking Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Individual: Case Report and Review of the Literature.

Case Rep Infect Dis 2018 26;2018:1891030. Epub 2018 Jul 26.

Department of Internal Medicine, Poona Hospital and Research Centre, Pune, India.

We present the first case report of cytomegalovirus (CMV) cholangiopathy as possible immune reconstitution inflammatory syndrome (IRIS) in a human immunodeficiency virus (HIV)-infected individual, within two months of starting effective HAART. The patient presented with abdominal pain, nausea, vomiting, decreased appetite, and jaundice. The patient was diagnosed on ERCP as AIDS cholangiopathy, and biopsy of the ampulla showed acute inflammation with CMV inclusion bodies. The patient underwent sphincterotomy with CBD stenting and HAART continued without use of ganciclovir or valganciclovir. On follow-up, the patient achieved clinical and histopathological cure, which was demonstrated on repeat ampullary biopsy.
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http://dx.doi.org/10.1155/2018/1891030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083534PMC
July 2018

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

AIDS Care 2018 12 18;30(12):1560-1566. Epub 2018 Jul 18.

a The Kirby Institute , UNSW Sydney , NSW , Australia.

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% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged >30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and >50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 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.
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http://dx.doi.org/10.1080/09540121.2018.1499859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181773PMC
December 2018

High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.

J Int Assoc Provid AIDS Care 2018 Jan-Dec;17:2325958218759211

1 Institute of Infectious Diseases, Mukund Nagar, Pune, Maharashtra, India.

Background: There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses.

Methods: We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history). Plasma viral loads (PVL) are performed 6 months post-initiation and annually thereafter. Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9 years) while median duration of ART prior to switching to MVC was 13 years. Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1 Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and sustained it for 2.3 years. Median CD4 count change from baseline was +117 (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months respectively. Repeat tropism among patients with virologic failure demonstrated R5 virus.

Conclusions: High rates of virologic failure was seen when MVC was used amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow up visit.

Results: Data on 13 PLHIV were analyze.
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http://dx.doi.org/10.1177/2325958218759211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748454PMC
September 2019

Cardiovascular Disease and Cardiovascular Disease Risk in HIV-Positive Populations in the Asian Region.

Open AIDS J 2017 21;11:52-66. Epub 2017 Aug 21.

The Kirby Institute, UNSW, Sydney, NSW 2052, Australia.

Introduction: Cardiovascular diseases (CVD) are becoming more prevalent in HIV-infected populations as they age largely due to improved treatment outcomes. Assessment of CVD risk and CVD risk factors in HIV-positive populations has focused on high income settings, while there are limited studies evaluating CVD in HIV-positive populations in the Asian region.

Materials And Methods: We provided an overview of the prevalence and incidence of CVD and its risk factors in adult HIV-positive populations, and of the strategies currently in place for CVD management in the Asian region.

Results: Studies from the Asian region showed that CVD and CVD risk factors, such as dyslipidaemia, elevated blood glucose, obesity and smoking, are highly prevalent in HIV-positive populations. A number of studies suggested that HIV infection and antiretroviral therapy may contribute to increased CVD risk. National HIV treatment guidelines provide some directions regarding CVD risk prevention and management in the HIV-infected population, however, they are limited in number and scope.

Conclusion: Development and consolidation of guidelines for integrated CVD and HIV care are essential to control the burden of CVD in HIV-positive populations. To inform guidelines, policies and practice in the Asian region, research should focus on exploring appropriate CVD risk screening strategies and estimating current and future CVD mortality and morbidity rates.
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http://dx.doi.org/10.2174/1874613601711010052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753029PMC
August 2017

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial.

J Bone Miner Res 2017 Sep 26;32(9):1945-1955. Epub 2017 Jun 26.

St Vincent's Hospital, Sydney, Australia.

Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. Because the relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomized trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (-2.5% versus -1.0%; difference -1.5%, 95% confidence interval [CI] -2.2 to -0.8, p < 0.001) and spine (-1.9% versus -0.4%; difference -1.6%, 95% CI -2.2 to -1.0, p < 0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, whereas hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related, or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis because of the reduced risk of serious clinical outcomes. Better understanding of the longer-term consequences of the observed reductions in BMD is needed.

Clinical Trials Registration: NCT00867048. © 2017 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555813PMC
September 2017

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

AIDS Res Ther 2017 5;14:27. Epub 2017 May 5.

Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Bangkok, 10400 Thailand.

Background: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome.

Methods: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created.

Results: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m (OR 2.4 vs. <18.5 kg/m; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count >350 cells/mm (OR 3.9 vs. <100 cells/mm; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm (OR 1.7 vs. <1000 cells/mm; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients.

Conclusion: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.
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http://dx.doi.org/10.1186/s12981-017-0151-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420083PMC
March 2018

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

Clin Infect Dis 2016 Dec 8;63(12):1668-1676. Epub 2016 Sep 8.

Center for Clinical AIDS Research and Education, David Geffen School of Medicine, University of California, Los Angeles.

Background:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.

Methods:  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.

Results:  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.

Conclusions:  Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms.
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http://dx.doi.org/10.1093/cid/ciw621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5146718PMC
December 2016

Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific.

PLoS One 2016 25;11(8):e0161562. Epub 2016 Aug 25.

TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.

Background: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use.

Methods: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression.

Results: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018).

Conclusions: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161562PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999237PMC
August 2017

Elevated CD8 T-cell counts and virological failure in HIV-infected patients after combination antiretroviral therapy.

Medicine (Baltimore) 2016 Aug;95(32):e4570

Department of Internal Medicine and AIDS Research Institute, Yonsei University College of Medicine, Seoul, Korea The Kirby Institute, UNSW Australia, Sydney, Australia Institute of Infectious Disease and Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore, Singapore Working Group on AIDS Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia Infectious Diseases Department, Bach Mai Hospital, Hanoi, Vietnam Queen Elizabeth Hospital and Integrated Treatment Centre, Hong Kong, China Hospital Sungai Buloh, Sungai Buloh, Malaysia HIV-NAT/Thai Red Cross AIDS Research Centre, Bangkok, Thailand Taipei Veterans General Hospital, Taipei, Taiwan University Malaya Medical Centre, Kuala Lumpur, Malaysia Beijing Ditan Hospital, Capital Medical University, Beijing, China Institute of Infectious Diseases, Pune, India Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand National Center for Global Health and Medicine, Tokyo, Japan Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia Chennai Antiviral Research and Treatment Clinical Research Site (CART CRS), YRGCARE Medical Centre, VHS, Chennai, India National Hospital for Tropical Diseases, Hanoi, Vietnam Research Institute for Tropical Medicine, Manila, Philippines Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Faculty of Medicine, Udayana University and Sanglah Hospital, Bali, Indonesia TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.

Elevated CD8 counts with combination antiretroviral therapy (cART) initiation may be an early warning indicator for future treatment failure. Thus, we investigated whether elevated CD8 counts were associated with virological failure (VF) in the first 4 years of cART in Asian HIV-infected patients in a multicenter regional cohort.We included patients from the TREAT Asia HIV Observational Database (TAHOD). Patients were included in the analysis if they started cART between 1996 and 2013 with at least one CD8 measurement within 6 months prior to cART initiation and at least one CD8 and viral load (VL) measurement beyond 6 months after starting cART. We defined VF as VL ≥400 copies/mL after 6 months on cART. Elevated CD8 was defined as CD8 ≥1200 cells/μL. Time to VF was modeled using Cox regression analysis, stratified by site.In total, 2475 patients from 19 sites were included in this analysis, of whom 665 (27%) experienced VF in the first 4 years of cART. The overall rate of VF was 12.95 per 100 person-years. In the multivariate model, the most recent elevated CD8 was significantly associated with a greater hazard of VF (HR = 1.35, 95% CI 1.14-1.61; P = 0.001). However, the sensitivity analysis showed that time-lagged CD8 measured at least 6 months prior to our virological endpoint was not statistically significant (P = 0.420).This study indicates that the relationship between the most recent CD8 count and VF was possibly due to the CD8 cells reacting to the increase in VL rather than causing the VL increase itself. However, CD8 levels may be a useful indicator for VF in HIV-infected patients after starting cART.
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http://dx.doi.org/10.1097/MD.0000000000004570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985340PMC
August 2016

Effects of unplanned treatment interruptions on HIV treatment failure - results from TAHOD.

Trop Med Int Health 2016 May 29;21(5):662-74. Epub 2016 Mar 29.

YRGCARE Medical Centre, Chennai, India.

Objectives: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.

Methods: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.

Results: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).

Conclusions: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.
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http://dx.doi.org/10.1111/tmi.12690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959847PMC
May 2016
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