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Screening for tuberculosis infection and effectiveness of preventive treatment among people living with HIV in low-incidence settings: a systematic review and meta-analysis

To determine the yield of screening for latent tuberculosis infection (LTBI) among people living with HIV (PLHIV) in low tuberculosis (TB) incidence countries (<10 TB cases per 100.000 persons), we performed a systematic review and meta-analysis to assess prevalence and predictive factors of LTBI, rate of TB progression, effect of TB preventive treatment (TPT), and numbers needed to screen. Pubmed and Cochrane Library were searched for studies reporting primary data, excluding studies on active or pediatric TB. We extracted LTBI cases, odds ratios, and TB incidences; pooled estimates using a random-effects model; and used the Newcastle-Ottawa scale for bias. In 51 studies with 65.930 PLHIV, 12% (95% CI 10–14) had a positive LTBI test, which was strongly associated with origin from a TB-endemic country (OR 4.7) and exposure to TB (OR 2.9). Without TPT (10,629 PLHIV), TB incidence was 28/1000 person years (PY; 95% CI 12–45) for LTBI-test positive versus 4/1000 PY (95% CI 0–7) for LTBI-test negative individuals. Among 625 PLHIV (1644 PY) receiving TPT, 15 developed TB (6/1000 PY). An estimated 20 LTBI-positive individuals would need TPT to prevent one case of TB, and numbers needed to screen to detect LTBI or prevent active TB varied according to a priori risk of LTBI. The relatively high prevalence of LTBI among PLHIV and the strong correlation with origin from a TB-endemic country support risk-stratified LTBI screening strategies for PLHIV in low-incidence countries and treating those who test positive.

Improvement in CD4 count among people with HIV in New York City, 2007-2021: a serial cross-sectional analysis

Background: A higher CD4 count among people with HIV (PWH) is associated with improved immune function and reduced HIV-related morbidity and mortality. The purpose of this analysis is to report the trend in CD4 count among PWH in New York City (NYC). Methods: We conducted a serial cross-sectional analysis using the NYC HIV registry data and reported the proportion of PWH with a CD4 count of 500 cells/mm3 or above, overall and by sex, race or ethnicity, and age. Results: The overall proportion of PWH in NYC with a CD4 count of 500 cells/mm3 or above increased from 38.1% in 2007 to 63.8% in 2021. Among males, the proportion increased from 36.7% in 2007 to 62.3% in 2021 with an annual percentage change (APC) of 6.6% (95% CI: 5.8, 7.5) in 2007–2013 and 2.6% (95% CI: 0.7, 4.4) in 2013–2017, and no changes in 2017–2021 (APC: 0.0%; 95% CI: -1.1, 1.0); among females, the proportion increased from 41.0% in 2007 to 67.6% in 2021 with an APC of 7.5% (95% CI: 5.2, 9.8) in 2007–2010, 4.5% (95% CI: 3.5, 5.4) in 2010–2015, and 0.8% (95% CI: 0.4, 1.2) in 2015–2021. White people had a higher proportion than other racial/ethnic groups, 70.9%, 59.3%, 60.9%, and 61.7%, respectively, among White, Black, Latino/Hispanic, and Asian/Pacific Islander males, and 69.8%, 68.0%, 66.3%, and 69.3%, respectively, among White, Black, Latina/Hispanic, and Asian/Pacific Islander females in 2021. Conclusions: CD4 count among PWH in NYC improved during 2007–2021, but the improvement slowed in recent years.

Vaginal microbiome, antiretroviral concentrations, and HIV genital shedding in the setting of hormonal contraception initiation in Malawi

Objective: To understand how vaginal microbiota composition affects antiretroviral concentrations in the setting of hormonal contraception initiation. Methods: Cervicovaginal fluid (CVF) concentrations of tenofovir, lamivudine, and efavirenz from 73 Malawian women living with HIV were compared before and after initiation of depot-medroxyprogesterone acetate (DMPA) or levonorgestrel implant. We evaluated antiretroviral concentrations and vaginal microbiota composition/structure in the context of contraception initiation and predicted genital shedding using multivariable repeated measurements models fit by generalized estimating equations. Results: Mean lamivudine CVF concentrations decreased 37% 1 month after contraception initiation. Subgroup analyses revealed a 41% decrease in women 1 month after initiating levonorgestrel implant, but no significant difference was observed in DMPA group alone. Tenofovir, lamivudine, and efavirenz CVF concentrations were positively correlated with anaerobic bacteria associated with non-optimal vaginal microbiota. Risk of genital HIV shedding was not significantly associated with tenofovir or lamivudine CVF concentrations (tenofovir RR: 0.098, p = 0.75; lamivudine RR: 0.142, p = 0.54). Lack of association between genital HIV shedding and efavirenz CVF concentrations did not change when adjusting for vaginal microbiota composition, and lamivudine/tenofovir CVF concentrations (RR: 1.33, p = 0.531). Conclusion: No effect of hormone initiation on genital shedding provides confidence that women with HIV on either DMPA or levonorgestrel implant contraception will not have compromised ART efficacy. The unexpected positive correlation between antiretroviral CVF concentrations and certain bacterial taxa relative abundance requires further work to understand the mechanism and clinical relevance.

Glottic Kaposi's sarcoma

Kaposi's sarcoma was first described by the Hungarian dermatologist Moritz Kaposi in 1872. This mysterious vascular tumor has since received increasing attention, especially after its association with AIDS was discovered in 1981. Kaposi's sarcoma is an indicative disease of AIDS, which is clinically divided into four forms: the classic (Mediterranean), endemic (African), epidemic (HIV/AIDS-associated), and iatrogenic (transplant-related). All four types share the same causative virus but have distinct epidemiological and clinical presentations [1,2]. Kaposi's sarcoma is now considered as a low-grade vascular tumor and is caused by Kaposi's sarcoma herpesvirus/human herpesvirus-8 (KSHV/HHV-8) infection [3,4]. It usually involves the skin, lymphatic system and viscera, most notably the respiratory and gastrointestinal tracts [5–7], whereas involvement of the glottis alone is rare. In particular, acute laryngeal obstruction occurs when Kaposi's sarcoma completely obstructs the glottis, which is life-threatening. This report summarized the clinical diagnosis and treatment of a case of AIDS complicated with glottic Kaposi's sarcoma. A 31-year-old man with HIV infection, had a history of homosexual sex. Antiviral drugs were stopped 2 years ago after antiretroviral therapy (ART) failure. Hoarseness and dyspnea occurred 3 months before admission without obvious inducement and became significantly worse after exercise. Since then, the symptoms gradually aggravated, and the patient were transferred to the infection department of our hospital for hospitalization. Fiberoptic bronchoscopy: under the microscope, purplish red nodules with different sizes of 0.3–0.8 cm are fused into clusters (Fig. 1a). Laboratory studies showed that antibody testing for HIV type 1 was positive. The viral load was 237 000 copies per milliliter (reference range, <40), and the CD4+ cell count was 2 per cubic millimeter (reference range, 500–1200). Glottic biopsy specimen staining with hematoxylin–eosin (HE) showed that spindle cell tumor (Fig. 1c) and immunohistochemical (IHC) testing for HHV-8 was positive (Fig. 1d). These findings were consistent with Glottic Kaposi's sarcoma. Highly active antiretroviral therapy regimen was treated with Albuvirtide+Twinaqt, and tracheotomy was performed. Two weeks after operation, the metal endotracheal tube was replaced. The patient breathed with tube, and was given liposomal doxorubicin 20 mg/m2 ivgtt D1 q3w chemotherapy for one course of treatment. After 3 months, laryngoscope was rechecked, and the glottic mucosa completely returned to normal (Fig. 1b). The patient's voice returned to normal without dyspnea. The metal endotracheal tube was successfully removed. After the tracheotomy fistula was closed, the patient continued to complete four chemotherapy courses, and then the rechecked viral load was less than 40 copies per milliliter, and the CD4+ cell count was 246 per cubic millimeter.Fig. 1: Fiberoptic bronchoscopy showed that there were multiple purplish red nodules of different sizes of 0.3–0.8 cm.Clinically, Kaposi's sarcoma mainly involves the skin and gastrointestinal mucosa, and only involving the glottis leading to acute respiratory obstruction is extremely rare. There is little clinical diagnosis and treatment experience. At present, there is no unified standard for the treatment of Kaposi's sarcoma. Radiotherapy, chemotherapy, local freezing, laser, surgical resection, and other methods can be selected, and HAART treatment needs to be restarted. For this rare case of AIDS complicated by glottis Kaposi's sarcoma with serious acute laryngeal obstruction and dyspnea, if not treated in time, it will lead to airway obstruction, even life-threatening. The patient had severe immune deficiency and extremely low CD4+ cells. If tracheotomy or thyrocricocentesis is performed according to the treatment principle of conventional patients to relieve airway obstruction, it may lead to incision infection, fistula nonunion, tracheal stenosis, and even sepsis and MODS. Therefore, in this case, we innovated the treatment mode, focusing on minimally invasive treatment, and selected the tracheal tube matching with the narrow airway through nasal tracheal intubation to open the airway to relieve airway obstruction, save lives, and win time for the next treatment; Then the oral cavity was chosen as the treatment path, with a wider field of vision exposure, and the glottis tumor was removed by high-frequency electrosection. To sum up, our treatment method can avoid trachea stenosis, intubation breathing and long-term inability to speak caused by incision infection, which will seriously affect the quality of life. Nasal intubation and oral treatment do not interfere with each other and have no impact on the operation. Furthermore, minimally invasive treatment eliminates new microorganisms, immediately relieves airway obstruction, is more conducive to retaining tissue samples, and is not easy to relapse after extubation. There are also few complications, a short hospitalization time, and a low cost. In conclusion, we summarized the diagnosis and treatment experience of this rare case, hoping to provide reference for the diagnosis and treatment of similar patient. Acknowledgements Conflicts of interest There are no conflicts of interest.

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