AIDS Research and Therapy最新文献

Introduction: Despite the widespread use of pre-exposure prophylaxis (PrEP) in preventing human immunodeficiency virus (HIV) transmission, scant information on HIV drug resistance mutations (DRMs) has been gathered over the past decade. This review aimed to estimate the pooled prevalence of pre-exposure prophylaxis and its two-way impact on DRM.

Methods: We systematically reviewed studies on DRM in pre-exposure prophylaxis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 guidelines. PubMed, Cochrane, and SAGE databases were searched for English-language primary studies published between January 2001 and December 2023. The initial search was conducted on 9 August 2021 and was updated through 31 December 2023 to ensure the inclusion of the most recent findings. The registration number for this protocol review was CRD42022356061.

Results: A total of 26,367 participants and 562 seroconversion cases across 12 studies were included in this review. The pooled prevalence estimate for all mutations was 6.47% (95% Confidence Interval-CI 3.65-9.93), while Tenofovir Disoproxil Fumarate/Emtricitabine-associated drug resistance mutation prevalence was 1.52% (95% CI 0.23-3.60) in the pre-exposure prophylaxis arm after enrolment. A subgroup analysis, based on the study population, showed the prevalence in the heterosexual and men who have sex with men (MSM) groups was 5.53% (95% CI 2.55-9.40) and 7.47% (95% CI 3.80-12.11), respectively. Notably, there was no significant difference in the incidence of DRM between the pre-exposure prophylaxis and placebo groups (log-OR = 0.99, 95% CI -0.20 to 2.18, I2 = 0%; p = 0.10).

Discussion: Given the constrained prevalence of DRM, the World Health Organization (WHO) advocates the extensive adoption of pre-exposure prophylaxis. Our study demonstrated no increased risk of DRM with pre-exposure prophylaxis (p > 0.05), which is consistent with these settings. These findings align with the previous meta-analysis, which reported a 3.14-fold higher risk in the pre-exposure prophylaxis group than the placebo group, although the observed difference did not reach statistical significance (p = 0.21).

Conclusions: Despite the low prevalence of DRM, pre-exposure prophylaxis did not significantly increase the risk of DRM compared to placebo. However, long-term observation is required to determine further disadvantages of extensive pre-exposure prophylaxis use. PROSPERO Number: CRD42022356061.

Background: The association between HIV infection and increased cardiometabolic risk, attributed to chronic inflammation in people living with HIV (PLWH) and/or antiretroviral therapy (ART) effects, has been inconsistent. In this study, we aimed to assess the associations of HIV-related factors with hypertension (HTN) and type-2 diabetes mellitus (T2DM), and the potential mediation effects of body mass index (BMI) in the associations between ART use and HTN or T2DM in PLWH in Cameroon.

Methods: A cross-sectional study was conducted with 14,119 adult PLWH from Cameroon enrolled in the International epidemiology Databases to Evaluate AIDS (IeDEA) between 2016 and 2021. HTN was defined as systolic/diastolic blood pressure ≥ 140/90 mmHg and/or current use of antihypertensive medication, while T2DM was defined as fasting blood sugar ≥ 126 mg/dL and/or use of antidiabetic medications. Univariable and multivariable multinomial logistic regression analyses examined the associations of factors with HTN alone, T2DM alone, and both (HTN + T2DM). Mediation analyses were conducted to assess the potential mediation roles of BMI, while controlling for age, sex, and smoking.

Results: Of the 14,119 participants, 9177 (65%) were women, with a median age of 42 (25^th-75th percentiles: 35-51) years. Age > 50 years was associated with HTN alone, T2DM alone, and HTN + T2DM compared to the age group 19-29 years. Men had higher odds of having HTN + T2DM. Overweight and obesity were predictors of HTN alone compared to being underweight. WHO stages II and III HIV disease were inversely associated with HTN alone compared to stage I. The odds of diabetes alone were lower with ART use. BMI partially mediated the association between ART use and hypertension, with a proportion of mediation effect of 49.6% (all p < 0.02). However, BMI did not mediate the relationship between ART use and diabetes.

Conclusions: Traditional cardiovascular risk factors were strongly associated with hypertension among PLWH, while HIV-related exposures had smaller associations. BMI partially mediated the association between ART use and hypertension. This study emphasizes the importance of screening, monitoring, and managing HTN and T2DM in older, male, and overweight/obese PLWH. Further research on the associations of HIV disease stage and ART use with HTN and T2DM is warranted.

Background: Despite the decreased incidence of the human immunodeficiency virus (HIV) in Tanzania, the number of adolescents living with HIV is increasing. This study aimed to describe factors independently associated with viral load non-suppression among adolescents living with HIV (ALHIV) on ART in the Tanga region.

Methods: We conducted a retrospective study of routinely collected data from ALHIV on ART from October 2018 to April 2022. We extracted data from the Care and Treatment Clinics form number 2 (CTC2) database that included age, sex, BMI, World Health Organization HIV clinical disease stage, marital status, ART duration, viral load suppression, facility level, and Dolutegravir (DTG)-based regimen. We did descriptive analysis using frequencies to describe the study participants' socio-demographic and clinical characteristics. The Cox proportional hazard regression model was used to identify factors associated with viral load non-suppression (VLS). Viral load non-suppression was defined as viral load ≥ 1000 copies/ml. A total of 4735 ALHIV on ART were extracted from CTC2, then 2485 were excluded (2186 missed viral load results, 246 were lost to follow-up, and 53 deaths).

Results: 2250 ALHIV on ART were tested for viral load, of whom 2216 (98.62%) adolescents were on first-line ART, and 2024 (89.96%) participants were virally suppressed, while 226 (10.04%) were virally non-suppressed. In addition, 2131 (94.71%) of participants were using a DTG-based regimen; of them, 1969 (92.40%) were virally suppressed. Not using a DTG-based regimen (HR: 9.36, 95% CI 3.41-15.31) and dispensary facility level (HR: 3.61, 95% CI 1.44-7.03) were independently associated with increased hazard for viral load non-suppression. In addition, adolescents aged between 15 and 19 years are less likely to be virally suppressed (HR: 0.55, 95% CI 0.30-0.99).

Conclusions: The dispensary facility level and not using a DTG-based regimen were significantly associated with viral load non-suppression. HIV intervention strategies should ensure a DTG-based regimen utilization in all adolescents living with HIV, and techniques used by higher-level health facilities should be disseminated to lower-level facilities.

Introduction: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited.

Methods: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose.

Results: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR.

Conclusions: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.

Background: Intestinal parasitic infections (IP) are a major source of morbidity in people living with Human immunodeficiency virus (HIV), particularly in resource-limited settings, mostly as a result of high viral load. Hence, this study aimed to investigate the magnitude of intestinal parasitic infections and its determinants among patients with HIV/AIDS attending public health facilities in East and West Gojam Zones in Ethiopia.

Methods: Institution-based cross-sectional study was conducted on 327 people living with HIV visiting public health facilities from December 2022 to May 2023. A simple random sampling technique was used to recruit participants. Face-to-face interviews were used to collect socio-demographics and determinants. The fresh stool was collected from each patient, transported, and tested in accordance with laboratory standard operating procedures of wet mount, formol-ether concentration technique, and modified acid-fast staining. Data were entered and analyzed in the statistical package for Social Science (SPSS) version 20. A 95% CI with p-value < 0.05 was considered statistically significant.

Results: The overall prevalence of IP in patients with HIV/AIDS was 19.3% (63/327). Hookworm was the most identified parasite 33.3% (21/63) followed by E.histolytica 17% (11/63) and G.lamblia 14.3% (9/63). Parasitic infections were significantly higher among viral load > 1000cps/ml (p = 0.035), WHO stage 4 (p = 0.002), CD4 < 200 cell/mm³ (p = 0.001), and bare foot walking (p = 0.001).

Conclusion: IP infections are moderately high among patients with HIV/AIDS in the study area. The proportion of parasites was greatly affected by high viral load, WHO stage 4, CD4 < 200 cell/mm³, and being barefoot; this gives valuable insight to health professionals, health planners and community health workers. As a result, viral load monitoring, and WHO stage controlling were periodically assessed in patients with HIV/AIDS. Health education, awareness creation, routine stool examination, and environmental hygiene were regularly advocated to increase the life of patients with HIV/AIDS.

Background: HIV early infant diagnosis (HEID) at the centralized laboratory faces many challenges that impact the cascade of timely HEID. Point of Care (PoC) HEID has shown to reduce test turnaround times, allow for task shifting and has the potential to reduce infant mortality. We aimed at assessing the feasibility of nurse based PoC-HEID in five facilities of Mbeya region.

Methods: We analysed data from healthcare workers at five obstetric health facilities that participated in the BABY study which enrolled mothers living with HIV and their HIV exposed infants who were followed up until 6 weeks post-delivery. Nurses and laboratory personnel were trained and performed HEID procedures using the Xpert HIV-1 Qual PoC systems. Involved personnel were interviewed on feasibility, knowledge and competency of procedures and overall impression of the use of HIV-1 Qual PoC system in clinical settings.

Results: A total of 28 health care workers (HCWs) who participated in the study between 2014 and 2016 were interviewed, 23 being nurses, 1 clinical officer, 1 lab scientist and 3 lab technicians The median age was 39.5 years. Majority of the nurses (22/24) and all lab staff were confident using Gene Xpert PoC test after being trained. None of them rated Gene Xpert handling as too complicated despite minor challenges. Five HCWs (5/24) reported power cut as the most often occurring problem. As an overall impression, all interviewees agreed on PoC HEID to be used in clinical settings however, about half of them (11/24) indicated that the PoC-HEID procedures add a burden onto their routine workload.

Conclusion: Overall, health care workers in our study demonstrated very good perceptions and experiences of using PoC HEID. Efforts should be invested on quality training, targeted task distribution at the clinics, continual supportive supervision and power back up mechanisms to make the wide-scale adoption of nurse based PoC HEID testing a possibility.

Background: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing.

Methods: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests.

Results: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001).

Conclusion: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.

Background: Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse transcriptase inhibitor-based regimens. Resolution of symptoms have occurred with switches to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; however, little is known regarding the development of angiolipomas when switching from NNRTI- to modern, integrase strand transfer inhibitor-based regimens. We describe a patient who underwent switch therapy from tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) to tenofovir alafenamide/FTC/bictegravir (TAF/FTC/BIC) who later developed angiolipomas.

Case presentation: A 55-year-old male had been on TDF/FTC/EFV for 8 years before switching to TAF/FTC/BIC. Nineteen months after antiretroviral switch, the patient presented with multiple lesions in the upper extremities and abdomen. Diagnostic biopsies revealed non-encapsulated angiolipomas and HHV-8 and non-alcoholic fatty liver disease was ruled out. New lesions continued to appear 29 months after ART switch, after which now lesions appeared and prior lesions remained stable with no increase in size noted. No surgical intervention or change in antiretroviral therapy was needed.

Conclusions: Angiogenesis may have been suppressed with TDF/FTC/EFV treatment, however when switched to TAF/FTC/BIC, promoted the growth of angiolipomas. Clinicians should be aware of the impact of switching to modern ART therapies resulting in possible adipogenesis.

Background: The COVID-19 pandemic has put the provision of health services globally at risk. In Sub-Saharan Africa, it had a major impact on HIV services. However, there is a lack of data on the post-pandemic period. This study aims to evaluate the resumption of HIV services and retention in care for adolescents and young people in the period following the COVID-19 pandemic.

Methods: A retrospective cohort study was conducted using interrupted time series analysis. Three periods were considered: pre-pandemic (form June 2019 to March 2020), pandemic (form April 2020 to March 2022) post-pandemic (from April 2022 to March 2023). Six outcome measures were considered: number of outpatient visits, HIV tests, HIV positivity ratio, the antiretroviral treatment (ART) non-adherence ratio, recall ratio, and the return ratio for adolescent and young adults on ART.

Results: During the study period, 447,515 outpatient visits and 126,096 HIV tests were recorded. After a reduction at the beginning of the pandemic period, both visits and tests increased during the pandemic (p < 0.05) and decreased in the post-pandemic (p < 0.05), recovering the pre-pandemic trends. The HIV positivity ratio slightly decreased from 3.3% to 1.7% during the study period (p < 0.05). The ART non-adherence ratio decreased from 23.4% to 2.4% throughout the study period (p < 0.05), with a drop at the beginning of the post-pandemic period (p < 0.05). The recall ratio increased during the study period (p < 0.05) with a drop at the beginning of the pandemic and post-pandemic periods (p < 0.05). The return ratio decreased at the beginning of the pandemic (p < 0.05) but returned to the pre-pandemic ratio in the post-pandemic period.

Conclusions: The post-pandemic values of the investigated outcomes were comparable to pre-pandemic period, or even improved. Differently from other services, such as the community activities, that have been severely affected by COVID-19 pandemic, the HIV service system has shown resilience following emergency situation.