Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan.

BACKGROUND: Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments. MATERIALS AND METHODS: In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included. RESULTS: From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001). CONCLUSIONS: After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.

Comparable clinical outcomes with same-day versus rapid initiation of antiretroviral therapy in Taiwan.

OBJECTIVES: WHO has recommended same-day antiretroviral therapy (SDART) initiation since 2017; however, higher attrition rates were noted in developing countries. METHODS: We included newly diagnosed people with HIV (PWH) from 2018 to 2022 at 18 hospitals around Taiwan. SDART initiation was defined as starting ART on the same day of HIV diagnosis and rapid initiation as starting ART within 14 days of diagnosis. A composite unfavorable outcome was defined as death after 30 days of diagnosis, loss to follow-up (LTFU), or virologic failure or rebound at 12 months. RESULTS: At 12 months, PWH on SDART initiation and those on rapid ART initiation showed similar rates of engagement in care with plasma HIV-1 RNA <50 copies/mL (87.5% vs 87.7%) and composite unfavorable outcome (7.7% vs 7.7%). PWH aged >30 years were less likely to have LTFU (aHR 0.44, 95% CI 0.28-0.70). PWH aged >30 years (aHR 0.59, 95% CI 0.41-0.85) and gay, bisexual, and men who have sex with men (GBMSM) (aHR 0.50, 95% CI 0.32-0.79) were less likely to have composite unfavorable outcomes. CONCLUSIONS: SDART and rapid ART initiation resulted in comparable clinical outcomes and viral suppression rates. PWH aged >30 years and GBMSM were less likely to have unfavorable outcomes.

Risky sexual practices and hepatitis C viremia among HIV-positive men who have sex with men in Taiwan.

BACKGROUND: Understanding the risk behaviors associated with sexually-transmitted hepatitis C virus (HCV) infection among men who have sex with men (MSM) may inform the public health policies and interventions aiming to achieve HCV microelimination. METHODS: HIV-positive MSM who had one of the following conditions were enrolled to undergo face-to-face questionnaire interviews to collect information on their sexual practices in the past 12 months: (1) elevation of aminotransferases in the past 6 months; (2) acquisition of sexually transmitted infections in the past 6 months; and (3) previous HCV infections. Plasma HCV RNA were tested at enrolment and every 3 months during follow-up. Baseline characteristics and risky behaviors were compared to identify factors associated with HCV viremia between HCV-viremic MSM and HCV-aviremic MSM in multivariate analysis. RESULTS: Among 781 MSM with a median age of 36 years, 57 (7.3%) had HCV viremia and 724 (92.7%) no HCV viremia during follow-up. A high proportion (38.9%) of the participants reported having used recreational drugs in the past 12 months, with 34.4% of them having slamming, but only 4.8% reported having shared their injection equipment. In multivariate analysis, use of recreational drugs (adjusted odds ratio [aOR], 2.14; 95% CI, 1.16-3.96), having participated in group sex (aOR, 2.35; 95% CI 1.24-4.40) and having had condomless receptive anal intercourse (aOR, 1.97; 95% CI 1.07-3.62) were significantly associated with HCV viremia. CONCLUSION: Among high-risk HIV-positive MSM, use of recreational drugs and risky sexual contacts were associated with HCV viremia, suggesting the mucosal contacts as the major route of HCV transmission.

Recently acquired hepatitis C virus infection among people living with human immunodeficiency virus at a university hospital in Taiwan.

BACKGROUND: Little is known about the engagement in hepatitis C virus (HCV) care and completion of HCV treatment in people living with human immunodeficiency virus (HIV) (PLWH) who have HCV coinfection in the Asia-Pacific region. Examining the HCV care cascade can identify barriers to the completion of HCV treatment and facilitate achievement of HCV micro-elimination in PLWH. AIM: To investigate the care cascade of incident HCV infections among PLWH in Taiwan. METHODS: PLWH with incident HCV infections, defined as HCV seroconversion, were retrospectively identified by sequential anti-HCV testing of all archived blood samples at National Taiwan University Hospital between 2011 and 2018. All PLWH with incident HCV infections were followed until December 31, 2019. The care cascade of HCV examined included all incident HCV-infected patients, the percentages of anti-HCV antibodies detected by HIV-treating physicians in clinical care, plasma HCV RNA load tested, HCV RNA positivity diagnosed, referral to treatment assessment made, anti-HCV treatment initiated, and sustained virologic response achieved. Those who had HCV seroconversion during the interferon (IFN) era (2011-2016) and the direct-acting antiviral (DAA) era (2017-2018) were analyzed separately. The duration of HCV viremia-from the date of seroconversion to viral clearance by treatments or until the end of observation-and the incidence of sexually transmitted infections (STIs) during the HCV viremic period were estimated. RESULTS: During the study period, 287 of 3495 (8.2%) PLWH (92.3% being men who have sex with men) who were HCV-seronegative at baseline developed HCV seroconversion by retrospective testing of all archived blood samples. Of the 287 incident HCV infections, 277 (96.5%) had anti-HCV antibodies detected by HIV-treating physicians, 270 (94.1%) had plasma HCV RNA determined and 251 (87.5%) tested positive for HCV RNA. Of those with HCV viremia, 226 (78.7%) were referred to treatment assessment, 215 (74.9%) initiated anti-HCV treatment, and 202 (70.4%) achieved viral clearance. Compared with that in the IFN era, the median interval from HCV seroconversion by retrospective testing to detection of HCV seropositivity by HIV-treating physicians was significantly shorter in the DAA era {179 d [interquartile range (IQR) 87-434] vs 92 d (IQR 57-173); P < 0.001}. The incidence rate of STIs in the DAA vs the IFN era was 50.5 per 100 person-years of follow-up (PYFU) and 38.5 per 100 PYFU, respectively, with an incidence rate ratio of 1.31 (95% confidence interval 0.96-1.77), while the duration of HCV viremia was 380 d (IQR 274-554) and 735 d (IQR 391-1447) (P < 0.001), respectively. CONCLUSION: While anti-HCV therapies are effective in achieving viral clearance, our study suggests more efforts are needed to expedite the linkage of PLWH diagnosed with incident HCV infections to HCV treatment.

Molecular diagnosis and therapy for cutaneous leishmaniasis of a returned traveler from Mexico.

Leishmaniasis is prevalent in Southern Europe, the Middle East, India, Africa, and Central and South America. Cutaneous leishmaniasis may spontaneously heal over time without treatment; however, risk of visceral dissemination and the impact of cosmetic defect are important concerns. We report a Case of cutaneous leishmaniasis in a patient who ever traveled to Mexico before the onset of a deteriorating wound around the swollen left eyebrow. A diagnosis of infection with Leishmania mexicana was made based on histopathological examination and molecular identification. Systemic treatment with liposomal amphotericin B and ketoconazole were administered with gradual healing of the lesion. Also, this traveler case implicates that the spread of endemic parasitic diseases may be a concealed risk on the public health for Taiwan underlying globalization.

Trends of recent hepatitis C virus infection among HIV-positive men who have sex with men in Taiwan, 2011-2018.

BACKGROUND: Increasing trends of HCV infection have been reported among HIV-positive men who have sex with men (MSM) in Europe, Australia and North America. The trends of recently acquired HCV infection among HIV-positive MSM are less clear in Asia-pacific region. METHODS: All HIV-positive patients seeking care at a university hospital in Taiwan tested for anti-HCV IgG at least once annually to estimate the incidence of HCV seroconversion during 2011-2018. HCV genotyping and sequencing were performed and multivariate logistic regression analysis was conducted to identify the factors associated with HCV seroconversion among MSM. FINDINGS: During the study period, 3495 HCV-seronegative patients (86·4% MSM) were included and 294 (8·4%) with recent HCV infection were identified, in whom 281 (95·6%) were MSM, during a total of 16,361·86 person-years of follow-up (PYFU), giving an overall incidence rate of 17·97 per 1000 PYFU, which increased from 14·28 per 1000 PYFU in 2011 to 25·38 per 1000 PYFU in 2018 (p<0·001). HCV seroconversion among MSM was associated with aspartate aminotransferase ≥37 U/L (adjusted odds ratio [AOR] 7·50, 95% CI 4·17-13·50), alanine aminotransferase ≥41 U/L (AOR 7·47, 95% CI 4·11-13·58), and syphilis acquisition (AOR 2·88, 95% CI 1·67-4·97). Among the 277 (94·2%) with HCV viremia, genotype 2a (n = 116) was the leading genotype, followed by 1b (n = 85), 6a (n = 34), and 1a (n = 21). Genotypes 3a and 6a increased from 0% and 5·2%, respectively, in 2011-2014 to 4·1% and 17·1% in 2015-2018. Phylogenetic analysis revealed increased clusters in genotypes 2a, 3a and 6a from 2011-2014 to 2015-2018. INTERPRETATION: An expanding HCV epidemic among HIV-positive MSM is occurring in Taiwan. Improving access to HCV testing and early linkage to treatment are needed to curb the expanding HCV epidemic. FUNDING: This research was supported by a grant from National Taiwan University Hospital, Taipei, Taiwan (NTUH.106-003347 to Hsin-Yun Sun).

HCV reinfections after viral clearance among HIV-positive patients with recent HCV infection in Taiwan.

BACKGROUND: Higher rates of hepatitis C virus (HCV) reinfection after viral clearance have been well described among HIV-positive men who have sex with men (MSM) in Europe. The epidemiology of HCV reinfection, however, has rarely been investigated among HIV-positive patients in Asia-Pacific region. METHODS: We retrospectively identified HIV-positive patients with recent HCV infection who had cleared their primary infection, either spontaneously or via treatment, between January 2011 and May 2018. All included patients were observed until 31 March 2019. HCV reinfection was defined as recurrent HCV viraemia after achieving viral clearance with anti-HCV treatment or after spontaneous clearance. RESULTS: During the study period, 219 HIV-positive patients (90.4% MSM) were diagnosed with recent HCV infection. Viral clearance with successful treatment was achieved in 108 patients (49.3%) and spontaneous clearance occurred in 20 (9.1%); of them, 18 (14.1%) acquired HCV reinfections, resulting in an incidence rate of 8.2 per 100 person-years of follow-up (95% CI 5.2-13.1). With the adjusted Cox proportional hazards model, we found a higher reinfection risk in patients with syphilis (adjusted hazard ratio 10.3, 95% CI 1.4-77.8, P = .023) compared to those without syphilis. HCV RNA testing, if performed only following syphilis and elevated aminotransferases, might miss 44.4% and 33.3% of HCV reinfections, respectively. CONCLUSIONS: Similar to the findings in Europe, we observed a high incidence of HCV reinfection among HIV-positive Taiwanese with recent HCV infection, which was significantly associated with syphilis. To identify HCV reinfections, annual HCV RNA testing should be instituted instead of testing driven by symptoms, syphilis or elevated aminotransferases.

Prolonged coma in a scrub typhus patient.

Central nervous system symptoms occur in more than 80% of patients with scrub typhus infection; however, the entity of central nervous system involvement is still not fully understood. We present the case of a patient with fulminant scrub typhus with multiple organ failure, including prolonged deep coma, and detail the sequential neurological symptoms, signs, laboratory data, and neuroradiological findings.