Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model

© 2022, The Author(s).Background: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. Methods: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. Results: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4–37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167–379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9–15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87–5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). Conclusion: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored

Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model

Background: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. Methods: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. Results: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4–37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167–379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9–15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87–5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). Conclusion: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored

Monocyte-to-lymphocyte ratio as a predictor of TB among people living with HIV

B A C K G R O U N D: Diagnostic tools to identify incipient or subclinical TB stages will be helpful for preventive intervention. A simple biomarker to predict TB may be the monocytes to lymphocytes ratio (ML ratio) in peripheral blood. M E T H O D S: We assessed the relationship between multiple time-updated ML ratio measurements and incidence of TB in people living with HIV (PLWH) after antiretroviral therapy (ART) was initiated. The ML ratio was updated at least every 6 months. TB incidence with corresponding 95% confidence intervals stratified according to time-updated ML ratio was calculated using ML ratio in quartiles. R E S U L T S: A total of 1305 PLWH were included in the analyses: 46 had incident TB and 1259 remained TB-free. The TB incidence rate was 10.3 (95% CI 7.1–14.9) cases/1000 patient-years (PYR) among participants with ML ratio ≥0.25 compared with 1.1/1000 PYR (95% CI 0.4–2.9) among those with ML ratio,0.15. At cut-point 0.23, the ML ratio provided a diagnostic area under the receiver operating characteristics curve (AROC) of 0.849 (95% CI 0.784–0.914) and a sensitivity of 85% and specificity of 71%. C O N C L U S I O N: Increased ML ratio was predictive of incident TB among PLWH on or after ART. The ML ratio can be a simple tool to stratify the risk of TB in PLWH

Monocyte-to-lymphocyte ratio as a predictor of TB among people living with HIV

B A C K G R O U N D: Diagnostic tools to identify incipient or subclinical TB stages will be helpful for preventive intervention. A simple biomarker to predict TB may be the monocytes to lymphocytes ratio (ML ratio) in peripheral blood. M E T H O D S: We assessed the relationship between multiple time-updated ML ratio measurements and incidence of TB in people living with HIV (PLWH) after antiretroviral therapy (ART) was initiated. The ML ratio was updated at least every 6 months. TB incidence with corresponding 95% confidence intervals stratified according to time-updated ML ratio was calculated using ML ratio in quartiles. R E S U L T S: A total of 1305 PLWH were included in the analyses: 46 had incident TB and 1259 remained TB-free. The TB incidence rate was 10.3 (95% CI 7.1–14.9) cases/1000 patient-years (PYR) among participants with ML ratio ≥0.25 compared with 1.1/1000 PYR (95% CI 0.4–2.9) among those with ML ratio,0.15. At cut-point 0.23, the ML ratio provided a diagnostic area under the receiver operating characteristics curve (AROC) of 0.849 (95% CI 0.784–0.914) and a sensitivity of 85% and specificity of 71%. C O N C L U S I O N: Increased ML ratio was predictive of incident TB among PLWH on or after ART. The ML ratio can be a simple tool to stratify the risk of TB in PLWH

Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model

BACKGROUND: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. METHODS: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. RESULTS: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4-37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167-379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9-15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87-5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). CONCLUSION: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored

Pharmacokinetics and 48-week safety and efficacy of generic lopinavir/ritonavir in Thai HIV-infected patients

Item does not contain fulltextBACKGROUND: Generic products reduce the costs of HIV treatment. Few generic second-line antiretroviral products are available. We assessed pharmacokinetics, safety and efficacy of generic lopinavir/ritonavir (LPV/r) produced by the Government Pharmaceutical Organization (GPO) of Thailand in Thai HIV-infected adults. METHODS: This was a single-arm prospective study. Patients with plasma HIV-1 RNA/=24 weeks, who were protease inhibitor (PI)-naive or experienced, were eligible. Patients started generic LPV/r tablets, 400/100 mg twice daily. At week 4, therapeutic drug monitoring was performed and analysed by validated HPLC. In patients using Kaletra((R)) (Abbott Laboratories, North Chicago, IL, USA) soft gel capsules (SGC) or generic LPV/r tablets produced by Mylan (Canonsburg, PA, USA; formerly Matrix, Hyderabad, India) prior to study entry, we compared the plasma minimum concentrations (Cmin) of the different formulations. Plasma HIV-1 RNA and safety were assessed until week 48. RESULTS: A total of 70 patients (32 males) were enrolled. Mean (sd) age was 40.7 (7.9) years and mean (sd) body weight was 60.3 (9.0) kg. Before study entry, all patients were virologically suppressed using a PI-based regimen; 62 (88.6%) were using LPV/r (Kaletra((R)) SGC n=22 and Mylan generic tablets n=40). Mean (sd) Cmin of GPO lopinavir and GPO ritonavir at week 4 were 7.1 (2.9) mg/l and 0.39 (0.21) mg/l, respectively, and not significantly different from the Cmin when taking Kaletra((R)) SGC or Mylan generic tablets. After 48 weeks, 95.6% of patients maintained plasma HIV-1 RNA<50 copies/ml. Four grade 3 and no grade 4 adverse events were reported. CONCLUSIONS: Generic LPV/r showed adequate levels, good tolerability and excellent 48-week efficacy

Efficacy and safety of a once-daily single-tablet regimen of tenofovir, lamivudine, and efavirenz assessed at 144 weeks among antiretroviral-naive and experienced HIV-1-infected Thai adults

OBJECTIVE: To assess the efficacy and safety of a new single-tablet regimen (STR) of tenofovir disoproxil fumarate (TDF) 300mg, lamivudine (3TC) 300mg, and efavirenz (EFV) 600mg in HIV-infected Thai patients. METHODS: This was a prospective study performed for 144 weeks among 51 treatment-naive patients and 49 experienced patients on separate tablets of TDF, 3TC, and EFV with HIV RNA<50 copies/ml. CD4, HIV RNA, liver and renal function, and lipid profiles were assessed at baseline, weeks 12, 24, and 48, and then every 24 weeks. RESULTS: The median baseline CD4 cell count was 512 cells/mul for treatment-experienced patients and 230 cells/mul for treatment-naive patients. Median baseline log10 HIV-1 RNA for treatment-naive subjects was 4.9 copies/ml. From the intention-to-treat (ITT) analysis, the proportion of subjects with HIV RNA <50 copies/ml at week 48, 96, and 144 was 95%, 94%, and 94%, respectively, for antiretroviral-experienced patients and 88%, 90%, and 80%, respectively, for antiretroviral-naive patients. One virological failure at week 12 had primary drug resistance of K70R, T69D, V75L. Three serious adverse events occurred (tension headache, infective endocarditis, and cervical dysplasia) and another three discontinued the study drug due to EFV intolerance. CONCLUSIONS: This generic STR TDF/3TC/EFV is effective and well-tolerated. These findings lend support to the use of this generic STR as first-line antiretroviral therapy in resource-limited settings

Pharmacokinetics of rilpivirine and 24-week outcomes after switching from efavirenz in virologically suppressed HIV-1-infected adolescents

Contains fulltext : 196253.pdf (publisher's version ) (Closed access)BACKGROUND: Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor drug, could be a favourable drug for maintenance therapy in HIV-infected adolescents because it has few long-term side effects. However, data among adolescents switching from efavirenz (EFV) to RPV are limited. This study investigated the pharmacokinetics (PK), safety and efficacy of RPV in virologically suppressed HIV-1-infected adolescents after switching from EFV. METHODS: Adolescents aged 12-18 years on EFV-based antiretroviral therapy (ART) were switched from EFV to RPV (25 mg, once daily). Intensive 24-h blood samplings at 0 (pre-dose), 1, 2, 4, 5, 6, 9, 12 and 24 h were performed 4 weeks after switching. PK parameters were calculated using a non-compartmental method and compared with published data from the PAINT and pooled ECHO/THRIVE substudies. HIV RNA level was measured at weeks 12 and 24. Biochemical profiles were measured at baseline and week 24. RESULTS: From January to June 2016, 20 adolescents (12 male) were enrolled. Median (IQR) age was 16 (15-17) years and weight was 49 (42-59) kg. Mean (sd) AUC24 h, C24 h and Cmax of RPV were 2,041 (745) ng*h/ml, 69 (29) ng/ml and 143 (65) ng/ml, respectively. Median (IQR) Tmax was 5 (2-9) h. Four adolescents had C24 h <40 ng/ml. All PK parameters were comparable with published data. All adolescents remained virologically suppressed at week 24. Significant decreases in fasting total cholesterol, triglyceride and low-density lipoprotein were observed (P-value <0.05). CONCLUSIONS: Virologically suppressed HIV-infected adolescents had adequate RPV exposure and remained virologically suppressed after switching from EFV. RPV can be used as long-term maintenance ART in HIV-infected adolescents