Pneumocystis Dihydropteroate Synthase Mutations in Patients with Pneumocystis Pneumonia Who Are Newly Diagnosed with HIV Infection

AbstractDifficult-to-treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are of concern in people living with HIV infection as they are more vulnerable to infection. We aimed to identify molecular characteristics of MRSA colonizing newly diagnosed HIV-infected adults in Tanzania. Individuals newly diagnosed with HIV infection were recruited in Dar es Salaam, Tanzania, from April 2017 to May 2018, as part of the randomized clinical trial CoTrimResist (ClinicalTrials.gov identifier: NCT03087890). Nasal/nasopharyngeal isolates of Staphylococcus aureus were susceptibility tested by disk diffusion method, and cefoxitin-resistant isolates were characterized by short-reads whole genome sequencing. Four percent (22/537) of patients carried MRSA in the nose/nasopharynx. MRSA isolates were frequently resistant towards gentamicin (95%), ciprofloxacin (91%), and erythromycin (82%) but less often towards trimethoprim-sulfamethoxazole (9%). Seventy-three percent had inducible clindamycin resistance. Erythromycin-resistant isolates harbored ermC (15/18) and LmrS (3/18) resistance genes. Ciprofloxacin resistance was mediated by mutations of the quinolone resistance-determining region (QRDR) sequence in the gyrA (S84L) and parC (S80Y) genes. All isolates belonged to the CC8 and ST8-SCCmecIV MRSA clone. Ninety-five percent of the MRSA isolates were spa-type t1476, and one exhibited spa-type t064. All isolates were negative for Panton-Valentine leucocidin (PVL) and arginine catabolic mobile element (ACME) type 1. All ST8-SCCmecIV-spa-t1476 MRSA clones from Tanzania were unrelated to the globally successful USA300 clone. Carriage of ST8 MRSA (non-USA300) was common among newly diagnosed HIV-infected adults in Tanzania. Frequent co-resistance to non-beta lactam antibiotics limits therapeutic options when infection occurs.

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Transmitted drug resistance to Tenofovir/Emtricitabine among persons with newly diagnosed HIV infection in Shenyang city, Northeast China from 2016 to 2018

BMC Infectious Diseases ◽

10.1186/s12879-021-06312-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhen Wang ◽

Bin Zhao ◽

Minghui An ◽

Wei Song ◽

Xue Dong ◽

...

Keyword(s):

Drug Resistance ◽

Hiv Infection ◽

Northeast China ◽

Transmitted Drug Resistance ◽

Newly Diagnosed ◽

Resistance Mutations ◽

Shenyang City ◽

Subtype B ◽

Recent Hiv Infection ◽

Hiv 1

Abstract Background To assess transmitted drug resistance (TDR) to tenofovir (TDF)/emtricitabine (FTC), using as pre-exposure prophylaxis, among newly diagnosed human immunodeficiency virus-1 (HIV-1)-infected residents in Shenyang city, northeast China. Methods Demographic and epidemiological information of all newly diagnosed HIV-1 infected residents in Shenyang city from 2016 to 2018 were anonymously collected from the local HIV epidemic database. HIV-1 pol sequences were amplified from RNA in cryopreserved plasma samples and sequenced directly. Viral subtypes were inferred with phylogenetic analysis and drug resistance mutations (DRMs) were determined according to the Stanford HIVdb algorithm. Recent HIV infection was determined with HIV Limiting Antigen avidity electro immunoassay. Results A total of 2176 sequences (92.4%, 2176/2354) were obtained; 70.9% (1536/2167) were CRF01_AE, followed by CRF07_BC (18.0%, 391/2167), subtype B (4.7%, 102/2167), other subtypes (2.6%, 56/2167), and unique recombinant forms (3.8%, 82/2167). The prevalence of TDR was 4.9% (107/2167), among which, only 0.6% (13/2167) was resistance to TDF/FTC. Most of these subjects had CRF01_AE strains (76.9%, 10/13), were unmarried (76.9%, 10/13), infected through homosexual contact (92.3%, 12/13), and over 30 years old (median age: 33). The TDF/FTC DRMs included K65R (8/13), M184I/V (5/13), and Y115F (2/13). Recent HIV infection accounted for only 23.1% (3/13). Most cases were sporadic in the phylogenetic tree, except two CRF01_AE sequences with K65R (Bootstrap value: 99%). Conclusions The prevalence of TDR to TDF/FTC is low among newly diagnosed HIV-infected cases in Shenyang, suggesting that TDR may have little impact on the protective effect of the ongoing CROPrEP project in Shenyang city.

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Epidemiological factors associated with recent HIV infection among newly-diagnosed cases in Singapore, 2013–2017

BMC Public Health ◽

10.1186/s12889-021-10478-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Li Wei Ang ◽

Carmen Low ◽

Chen Seong Wong ◽

Irving Charles Boudville ◽

Matthias Paul Han Sim Toh ◽

...

Keyword(s):

Early Diagnosis ◽

Hiv Infection ◽

Hiv Transmission ◽

Risk Groups ◽

Newly Diagnosed ◽

Hiv Diagnosis ◽

Factors Associated ◽

Epidemiological Factors ◽

Voluntary Testing ◽

Recent Hiv Infection

AbstractBackgroundEarly diagnosis is crucial in securing optimal outcomes in the HIV care cascade. Recent HIV infection (RHI) serves as an indicator of early detection in the course of HIV infection. Surveillance of RHI is important in uncovering at-risk groups in which HIV transmission is ongoing. The study objectives are to estimate the proportion of RHI among persons newly-diagnosed in 2013–2017, and to elucidate epidemiological factors associated with RHI in Singapore.MethodsAs part of the National HIV Molecular Surveillance Programme, residual plasma samples of treatment-naïve HIV-1 positive individuals were tested using the biotinylated peptide-capture enzyme immunoassay with a cutoff of normalized optical density ≤ 0.8 for evidence of RHI. A recent infection testing algorithm was applied for the classification of RHI. We identified risk factors associated with RHI using logistic regression analyses.ResultsA total of 701 newly-diagnosed HIV-infected persons were included in the study. The median age at HIV diagnosis was 38 years (interquartile range, 28–51). The majority were men (94.2%), and sexual route was the predominant mode of HIV transmission (98.3%). Overall, 133/701 (19.0, 95% confidence interval [CI] 16.2–22.0%) were classified as RHI. The proportions of RHI in 2015 (31.1%) and 2017 (31.0%) were significantly higher than in 2014 (11.2%). A significantly higher proportion of men having sex with men (23.4, 95% CI 19.6–27.6%) had RHI compared with heterosexual men (11.1, 95% CI 7.6–15.9%). Independent factors associated with RHI were: age 15–24 years (adjusted odds ratio [aOR] 4.18, 95% CI 1.69–10.31) compared with ≥55 years; HIV diagnosis in 2015 (aOR 2.36, 95% CI 1.25–4.46) and 2017 (aOR 2.52, 95% CI 1.32–4.80) compared with 2013–2014; detection via voluntary testing (aOR 1.91, 95% CI 1.07–3.43) compared with medical care; and self-reported history of HIV test(s) prior to diagnosis (aOR 1.72, 95% CI 1.06–2.81).ConclusionAlthough there appears to be an increasing trend towards early diagnosis, persons with RHI remain a minority in Singapore. The strong associations observed between modifiable behaviors (voluntary testing and HIV testing history) and RHI highlight the importance of increasing the accessibility to HIV testing for at-risk groups.

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Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase (dhps) Gene Mutations in HIV-Infected Persons in Uganda

PLoS ONE ◽

10.1371/journal.pone.0049991 ◽

2012 ◽

Vol 7 (11) ◽

pp. e49991 ◽

Cited By ~ 14

Author(s):

Steve M. Taylor ◽

Steven R. Meshnick ◽

William Worodria ◽

Alfred Andama ◽

Adithya Cattamanchi ◽

...

Keyword(s):

Gene Mutations ◽

Pneumocystis Pneumonia ◽

Dihydropteroate Synthase ◽

High Prevalence ◽

Dhps Gene ◽

Low Prevalence

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Difficulties in primary diagnosis of HIV infection at the stages of health care settings

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid35187 ◽

2020 ◽

Vol 25 (1) ◽

pp. 11-17

Author(s):

Elena V. Esaulenko ◽

Kseniya E. Novak ◽

Thierry Ingabire ◽

Sof’ya A. Semenova ◽

Aleksandra O. Nikiforova

Keyword(s):

Infectious Diseases ◽

Hiv Infection ◽

Primary Care Physicians ◽

Sexual Transmission ◽

Laboratory Data ◽

Primary Diagnosis ◽

Newly Diagnosed ◽

Hiv Diagnosis ◽

Rapid Tests ◽

First Time

Aim: to demonstrate the difficulties and timeliness of HIV diagnosis by primary care physicians, to carry out a clinical and epidemiological analysis of newly diagnosed cases of HIV infection. Materials and methods: The study evaluated the routing of diagnosis and analyzed the epidemiological and clinical and laboratory data of 85 patients with a newly diagnosed HIV infection hospitalized in the St. Petersburg Clinical Infectious Diseases Hospital named after S. P. Botkin during the period from November 2018 to October 2019. To confirm positive results, ELISA and western blot were used. Results: Among the observed patients, 71.3% were women and 28.7% were men. The average age was 39.3 2 years. Upon admission to the infectious diseases hospital with an established diagnosis of HIV infection, 49.5% were hospitalized in specialized departments (n = 42). Of them, nine (9) were referred by the polyclinic with an established diagnosis, in 20 patients the diagnosis was established in somatic hospitals, and emergency room doctors newly diagnosed HIV infection in 13 more patients. The remaining 50.5% (n = 43) were hospitalized in various departments with other diagnoses. Clinical and laboratory analysis of these patients showed that for the first time in life, an established diagnosis of HIV infection corresponded to both early (15.3%) and late (84.7%) stages of the disease with dominance of sexual transmission of the virus (43.6%). Conclusion: HIV infection at both early and late stages can manifest under the guise of various other diseases, which makes it necessary to expand testing of patients for HIV infection, including using rapid tests.

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The outcome predictors and therapeutic strategy of pneumocystis pneumonia in North China: a double-center retrospective study

10.21203/rs.2.9235/v1 ◽

2019 ◽

Author(s):

Wei Hua ◽

Yang Yang ◽

Zheng Zhang ◽

Wei Zhang ◽

Jing Zeng ◽

...

Keyword(s):

Hiv Infection ◽

Side Effect ◽

Therapeutic Strategy ◽

North China ◽

Pneumocystis Pneumonia ◽

Parameter Distribution ◽

Glucocorticoid Treatment ◽

Cell Counts ◽

Cd4 Cell Counts ◽

Cd4 Cell

Abstract Background: Pneumocystis pneumonia (PCP) is common in HIV/AIDS patients with advanced immunosuppression. Trimethoprim/sulfamethoxazole (TMP/SMX) is recommended as the first-line anti-pneumocystis agent as soon as PCP is suspected based on its typical feature. However, the clinical characteristic and therapeutic strategy of Chinese PCP were not well-known. Methods: We retrospectively investigated 473 HIV associated PCPs in North China from double centers, Beijing You An Hospital during 2010 to 2017 and the Infectious Disease Hospital in Harbin during 2015 to 2017. HIV associated PCP were diagnosed as the guideline recommended by CDC, NIH and HIV Medicine Association of IDSA. Demographic and clinic data were collected and statistically analysed as the parameter distribution feature. Results: Among 473 HIV associated PCPs, we found that men were over-represented in PCP due to the high incidence of HIV infection among male homosexuality, and over one-third of them were aware of their HIV infection ago but did not maintain effective antiretroviral therapy. A history of smoking and multi-organism infection or system infection were common among them. In the multivariate analysis, we found lactate dehydrogenase (LDH) (OR 1.020, 95% CI 1.006-1.033, P=0.005), alveolar-arterial O2 difference ([A-a] DO2) and neutrophils counts (OR 1.051, 95% CI 1.005-1.099, P=0.030) were unfavourable predictors and CD4 cell counts (OR 0.900, 95% CI 0.813-0.996, P=0.041) were favourable predictor of PCP outcome. Trimethoprim/sulfamethozole (TMP/SMZ) but not TMP/SMX was used to anti-pneumocystis therapy in these patients with a low side-effect incidence which mainly forcused on epispasis, fever, liver injury and myelosuppression. Caspofungin was the only alternative medicine for those presented poor efficacy or could not tolerate the side-effects of TMP-SMZ and near 30 percent of moderate/severe PCP received glucocorticoid treatment. Conclusion: The present data suggest that high levels of serum-LDH, [A-a] DO2 and neutrophils counts and low CD4 cell counts predict poor outcome of PCP. TMP/SMZ can cure most PCPs with a low side-effect incidence and caspofungin is an effective alternation. A larger prospective study is needed to obtain better estimates of PCP in China.

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