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Coronavirus disease 2019 (COVID-19) was first detected in December 2019. In March 2020, the World Health Organization declared COVID-19 a pandemic. People with underlying medical conditions may be at greater risk of infection and experience complications from COVID-19. COVID-19 has the potential to affect People living with HIV (PLWH) in various ways, including be increased risk of COVID-19 acquisition and interruptions of HIV treatment and care. The purpose of this review article is to evaluate the impact of COVID-19 among PLWH. The contents focus on 4 topics: (1) the pathophysiology and host immune response of people infected with both SARS-CoV-2 and HIV, (2) present the clinical manifestations and treatment outcomes of persons with co-infection, (3) assess the impact of antiretroviral HIV drugs among PLWH infected with COVID-19 and (4) evaluate the impact of the COVID-19 pandemic on HIV services.

Evidence has demonstrated inferior humoral immune responses after SARS-CoV-2 vaccination in kidney transplant recipients compared to the general population. However, data on cellular immune responses in this population have not been established. We searched the MEDLINE, Scopus, and Cochrane databases and included studies reporting cellular immune response rates in kidney transplant recipients after receiving SARS-CoV-2 vaccines. Studies that reported factors associated with cellular immune responders or non-responders were also included (PROSPERO: CRD42022375544). From a total of 1,494 articles searched, 53 articles were included in the meta-analysis. In all, 21 studies assessed cellular immune response by interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISPOT), 22 studies used interferon-γ release assay (IGRA), and 10 studies used flow cytometric analysis. The pooled response rate after two doses (standard regimen) and three doses of vaccination was 47.5% (95%CI 38.4-56.7%) and 69.1% (95%CI 56.3-80.6%) from IFN-γ ELISPOT, 25.8% (95%CI 19.7-32.4%) and 14.7% (95%CI 8.5-22.2%) from IGRA, and 73.7% (95%CI 55.2-88.8%) and 86.5% (95%CI 75.3-94.9%) from flow cytometry, respectively. Recipients with seroconversion were associated with a higher chance of having cellular immune response (OR 2.58; 95%CI 1.89-3.54). Cellular immune response in kidney transplant recipients was lower than in dialysis patients (OR 0.24; 95%CI 0.16-0.34) and the general population (OR 0.10; 95%CI 0.07-0.14). Age and immunosuppressants containing tacrolimus or corticosteroid were associated with inferior cellular immune response. Cellular immune response after SARS-CoV-2 vaccination in kidney transplant recipients was lower than in dialysis patients and the general population. Age, tacrolimus, and corticosteroid were associated with poor response. Cellular immune response should also be prioritized in vaccination studies. https://www.crd.york.ac.uk/prospero/, identifier CRD42022375544.

Background Prisons are considered as major reservoirs for tuberculosis. Preventive therapy for latent TB infection (LTBI) is an adjunctive strategy to control TB. However, LTBI data in Thai prisoners is limited. This study assessed the prevalence of LTBI and feasibility of isoniazid preventive therapy (IPT). Methods A cross-sectional study was conducted among prisoners in Klong Prem Central Prison, Bangkok. Participants were screened for active TB by questionnaire and chest X-ray. LTBI was evaluated by Tuberculin skin test (TST) and QuantiFERON-TB Gold Plus (QFTP) among subgroup. Participants with positive TST or QFTP were considered to have LTBI. Participants with LTBI were offered IPT. Results From August 2018–November 2019, 1002 participants were analyzed. All participants were male with a median age of 38 (IQR 32–50) years. LTBI identified by either TST/QFTP was present in 466 (46.5%) participants. TST was positive in 359 (36%) participants. In the subgroup of 294 participants who had both TST and QFTP results, 181/294 (61.6%) tested positive by QFTP. Agreement between TST and QFTP was 55.1% (Kappa = 0.17). The risk factors associated with LTBI were previous incarceration (aOR 1.53, 95%CI, 1.16–2.01, p  = 0.002), history of prior active TB (aOR 3.02, 95%CI, 1.74–5.24, p  < 0.001) and duration of incarceration ≥10 years (aOR 1.86, 95%CI, 1.24–2.79, p  = 0.003). Majority of LTBI participants (82%) agreed to take IPT. Three hundred and 56 (93%) participants completed treatment whereas 27 (7%) participants discontinued IPT due to the side effects of INH. Conclusion This is the first study to evaluate the prevalence of LTBI and feasibility of IPT among Thai prisoners. LTBI prevalence in male prisoners in Thailand is high. LTBI screening and treatment should be implemented together with other preventive components.

Background Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has become the preferred drug for the treatment of HIV-1 and chronic hepatitis B infection in clinical practice. Results from clinical trials showed that it had better renal and bone mineral outcomes compared to tenofovir disoproxil fumarate (TDF). However, as we have seen with TDF, side effects from the new medication can be more prevalent and recognized after extensive use in real world situations. Sporadic cases of acute kidney injury in patients using TAF have started to emerge. Case presentation We report a case of 49-year-old Thai, HIV treatment-experienced female with hypertension presented with worsening renal function after switching her antiretroviral regimen from TDF, emtricitabine (FTC), and lopinavir/ritonavir (LPV/r) to TAF, FTC and dolutegravir (DTG) for 3 months. Kidney biopsy showed distinctive picture of tenofovir nephrotoxicity with acute tubular injury and mitochondrial injury. The possible causes of acute kidney injury and nephrotoxicity from TAF for this patient were discussed. We have extensively reviewed all published case reports of TAF-associated nephrotoxicity and summarized the essential information in this article. Conclusion Although TAF has less nephrotoxicity compared with TDF; renal function should always be monitored after the initiation of both drugs. Future large cohort studies are required to identify the risk factors of TAF-associated nephrotoxicity and to design an effective preventive strategy.

Background Immune restoration is often incomplete after ART in HIV patients, both quantitatively and qualitatively. We studied the incidence and probability of CD4/CD8 normalization in an adult Thai HIV cohort and explored the predictive value of the ratio for developing of non-AIDS defining events (NAEs). Methods We analyzed data from HIV-infected Thai adults between 1996 and 2017 in the HIV-NAT 006 prospective long-term cohort in Bangkok, Thailand. Normalization was defined as CD4/CD8 ratio ≥ 1 on two consecutive visits, and normalization probability was calculated using the Kaplan–Meier method. NAEs were a composite endpoint including cardiovascular or cerebrovascular diseases, chronic kidney diseases, non-AIDS defining malignancies and death. Multivariate Cox regression was used to evaluate demographic, disease and treatment characteristics associated with CD4/CD8 ratio normalization and NAEs. Results A total of 800 ART-naïve patients with baseline CD4/CD8 ratio of < 0.8 who started combination ART, and had sustained virological suppression were enrolled. Participants were on ART for a median of 8.9 years and virologically suppressed for 6.1 years. The probabilities of CD4/CD8 normalization at 2, 5 and 10 years after virological suppression were 5.1%, 18.6% and 39.1%, respectively. Factors associated with normalization in multivariate analysis were female sex (hazard ratio [HR]: 2.47, 95% CI 1.71–3.56, p < 0.001) and baseline CD4 counts ≥ 350 cells/mm 3 (HR: 3.62, 95% CI 2.36–5.55), p < 0.001) vs. < 200 cells/mm 3 as reference. The second analysis explored the predictive value of CD4/CD8 ratio for NAEs. Older age (HR: 1.09, 95% CI 1.05–1.13, p < 0.01) and current CD4/CD8 ratio < 0.3 (HR: 3.02, 95% CI 1.27–7.21, p = 0.01) or between 0.3 and 0.45 (HR: 2.03, 95% CI 1.03–3.98, p = 0.04) vs. > 0.45 were independently associated with higher risk of progression to NAEs in the multivariate analysis. Conclusions Our findings showed that complete immune recovery is uncommon in an Asian setting and earlier ART initiation at higher CD4 counts may have increased the ratio sooner. The findings demonstrate the use of CD4/CD8 ratio as a prognostic marker for clinical progression of NAEs. Trial registration HIV-NAT 006 cohort, clinical trial number: NCT00411983

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/mm 3 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/mm 3 . The overall crude incidence of TB was 4.66 (95% CI 3.87–5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m 2 , 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.

Background Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART). Methods We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry. Results The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069–0.123) compared to controls (0.055; IQR 0.045–0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB ( p  = 0.005), but there was no correlation in controls. Conclusions The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts. Trial registration ClinicalTrials.gov Identifier: NCT00411983.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m2; women: 23.1 vs. 24.7 kg/m2] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15–21) years in men and 18 (IQR 15–21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5–8.9) years in men and 8.2 (IQR 6.1–10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm2) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983.

There are limited data regarding bone health in older people living with HIV (PWH), especially those of Asian ethnicity. We aimed to determine whether BMD in well-suppressed HIV-infected men and women aged ≥ 50 years are different from HIV-uninfected controls. In a cross-sectional study, BMD by dual-energy X-ray absorptiometry and calciotropic hormones were measured. A total of 481 participants were consecutively enrolled (209 HIV+ men, 88 HIV- men, 126 HIV+ women and 58 HIV- women). PWH were on average 2.5 years younger [men: 55.0 vs. 57.5 yr; women: 54.0 vs. 58.0 yr] and had lower body mass index (BMI) [men: 23.2 vs. 25.1 kg/m 2 ; women: 23.1 vs. 24.7 kg/m 2 ] compared to the controls. The median duration since HIV diagnosis was 19 (IQR 15–21) years in men and 18 (IQR 15–21) years in women. Three-quarters of PWH had been treated with tenofovir disoproxil fumarate-containing antiretroviral therapy for a median time of 7.4 (IQR 4.5–8.9) years in men and 8.2 (IQR 6.1–10) years in women. In an unadjusted model, HIV+men had significantly lower BMD (g/cm 2 ) at the total hip and femoral neck whereas there was a tend toward lower BMD in HIV+women. After adjusting for age, BMI, and other traditional osteoporotic risk factors, BMD of virologically suppressed older PWH did not differ from participants without HIV (P>0.1). PWH had lower serum 25(OH)D levels but this was not correlated with BMD. In conclusion, BMD in well-suppressed PWH is not different from non-HIV people, therefore, effective control of HIV infection and minimization of other traditional osteoporosis risk factors may help maintain good skeletal health and prevent premature bone loss in Asian PWH. Clinical trial registration: Clinicaltrials.gov # NCT00411983 .

Tuberculosis is the most common opportunistic infection in individuals with HIV, and rifampicin is crucial in the treatment of tuberculosis. Drug–drug interactions complicate the use of DTG in HIV/TB co‐infection, which makes drug administration more difficult. This study aimed to develop the population pharmacokinetic model of DTG when co‐administered with rifampicin. The developed model was further used to investigate different dosing regimens. Forty HIV/TB‐co‐infected participants receiving DTG 50 mg once daily (OD) with food or DTG 50 mg twice daily (b.i.d.) without food were included in the analysis. Intensive pharmacokinetic samples were collected. The data were analyzed using a nonlinear mixed‐effects modeling approach. A total of 332 DTG concentrations from 40 PLWH were analyzed. The pharmacokinetics of DTG co‐administered with rifampicin can be best described by a one‐compartment model with first‐order absorption (incorporating lag time) and elimination. Total bilirubin was the only covariate that significantly affected CL/F. DTG 50 mg b.i.d. results in the highest proportion of individuals achieving in vitro IC90 of 0.064 mg/L and in vivo EC90 of 0.3 mg/L, while more than 90% of individuals receiving DTG 100 mg OD would achieve the in vitro IC90 target. Therefore, DTG 100 mg OD could serve as an alternative regimen by minimizing the difficulty of drug administration. However, its clinical efficacy requires additional evaluation.