AIDS Research and Therapy最新文献

Background: People living with HIV (PLWH) are at increased risk of stroke due to many factors including possibly antiretroviral therapy (ART) use. We sought to evaluate the association between ART type and duration of use with stroke in PLWH.

Methods: We conducted a prospective exploratory case-control study at the University Teaching Hospital in Lusaka, Zambia between March 2022 and October 2024 in adult (≥ 18 years) PLWH comparing those with stroke (cases) and without (controls) matched (1:2) for age, sex and race. Standardized data collection instruments were used to collect clinical, laboratory and imaging information. This information was compared between the cases and controls using Chi-square, t-tests, Mann-Whitney U-test (not normally distributed) and multivariable conditional logistic regression analyses with subgroup analysis by ART duration done for the cases.

Results: We analyzed results for 205 cases and 410 controls. Compared to controls, cases were more likely to have hypertension (71% vs. 18%, p = 0.001), lower CD4 counts [293(163-592) cells/µl vs. 533 (376-688) cells/µl, p = 0.0001] and to be on second line ART (23% vs. 4%, p = 0.001). Hypertension (aOR 19.7, 95% CI 3.1-126.4, p = 0.002) and Tenofovir Disoproxil Fumarate (TDF) use (aOR 85.3, 95% CI 5.3-1380.7, p = 0.002) were associated with increased odds of stroke, whereas Dolutegravir (aOR 0.03, 95% CI 0.001-0.58, p = 0.02) and alcohol use (aOR 0.24, 95% CI 0.06-0.95) were associated with reduced odds of stroke. The majority of stroke patients on long-term ART were using Dolutegravir (80% vs. 35%, p = 0.001) and TDF (72% vs. 42%, p = 0.01).

Conclusion: In PLWH, TDF associates with higher odds of stroke. Although Dolutegravir associates with reduced odds of stroke, stroke patients on long-term ART are more likely to be on it.

Background: This study aimed to evaluate the diagnostic utility of metagenomic next-generation sequencing (mNGS) in detecting pulmonary infections in persons living with HIV(PLWH).

Methods: We conducted a retrospective study involving 246 PLWH with pulmonary infections. Bronchoalveolar lavage fluid (BALF) specimens were collected from all patients. mNGS and traditional microbial cultures were performed in parallel to compare the differences in pathogen identification. Patients were stratified by immune status based on CD4⁺ T cell counts, and the association between pathogen profiles and immunodeficiency severity was analyzed.

Results: mNGS demonstrated a significantly higher pathogen detection sensitivity (98.0%) compared to traditional cultures (32.1%). The spectrum of pathogens detected by mNGS and culture methods differed significantly. mNGS identified 123 pathogenic microorganisms, whereas cultures detected only 17. mNGS detected additional pathogens, including viruses (e.g., Epstein-Barr virus and cytomegalovirus) and fastidious microorganisms (e.g., Pneumocystis jirovecii). Furthermore, mNGS revealed a significant correlation between PLWH-associated immunodeficiency and pathogen profiles. The diversity of pathogens, particularly fungi and viruses, increased with declining CD4⁺ T cell counts (p < 0.05).

Conclusion: mNGS comprehensively characterizes the complex pathogen spectrum in PLWH-associated pulmonary infections, significantly enhancing detection sensitivity for mixed and fastidious infections, thereby guiding targeted anti-infective therapy. Immunosuppression severity strongly correlates with opportunistic pathogen profiles and the risk of specific pathogen detection, highlighting the importance of immune status-guided clinical strategies. mNGS serves as a valuable adjunct to conventional diagnostic methods, enhancing the detection and prognostic assessment of infectious complications in PLWH.

Background: Vitamin B12 deficiency is a common but under-recognized comorbidity among HIV-infected individuals, contributing to anemia, neurological impairment, and poor immune recovery. In sub-Saharan Africa, where HIV burden is high, routine screening for B12 deficiency is rarely performed, and data in Uganda are scarce. This study aimed to determine the prevalence of vitamin B12 deficiency, identify associated factors, and examine its correlation with CD4 count among HIV-positive adults.

Methods: We conducted a cross-sectional study among 156 HIV-positive adults at Kayunga Regional Referral Hospital, Uganda. Serum vitamin B12 was measured using the ARCHITECT B12 assay. Deficiency was defined as < 200 pg/mL. Logistic regression and Spearman correlation were used to identify predictors and assess relationships with CD4 counts.

Results: Vitamin B12 deficiency was present in 25% of participants. Significant independent predictors included: low income (aOR 2.5, 95% CI 1.07-5.75), ART-naïve status (aOR 2.9, 95% CI 1.03-8.73), underweight BMI (aOR 4.2, 95% CI 1.89-9.60), and HIV duration > 10 years (aOR 4.0, 95% CI 1.32-12.1). CD4 count showed a modest inverse correlation (ρ = - 0.24, p < 0.001).

Conclusion: Vitamin B12 deficiency is prevalent among HIV-positive adults in Uganda. Routine screening and nutritional interventions are recommended, especially for high-risk groups.

Background: This systematic review and meta-analysis assessed viral suppression among adults receiving WHO-recommended first-line dolutegravir-based ART in programmatic settings in low- and middle-income countries (LMICs).

Methods: A systematic search of Ovid MEDLINE, Embase, and major HIV conferences (IAS, AIDS, and CROI) from January 2019 to September 2024 identified cohort and cross-sectional studies reporting viral suppression among adults receiving WHO-recommended first-line dolutegravir-based ART in LMICs. Studies with follow-ups ≤ 4 months or using non-WHO-recommended regimens were excluded. Pooled estimates were calculated using random-effects meta-analysis. Sensitivity analyses excluded outliers. Subgroup analyses distinguished adults initiating versus transitioning to dolutegravir-based ART. Both on-treatment and intention-to-treat outcomes were assessed.

Results: Twenty-two studies (n = 47 to 50,742) from 13 countries were included. On-treatment pooled viral suppression was 95% (95% CI: 91-97%, I²= 96%) at six months, 96% (94-98%, I² = 97%) at 12 months, and 98% (96-99%, I² = 94%) at 24 months. Sensitivity analysis removing outliers decreased heterogeneity and slightly lowered the 6‑month estimate (to 94%), with negligible change at 12 months. At 6 months, viral suppression was higher in those transitioning than initiating ART (98% vs. 94%, p < 0.01), with similar rates at 12 months (97%, p = 0.67). The pooled intention-to-treat 12-month viral suppression rate was 89% (82-93%, I² = 95%), with no significant difference by ART status (initiating 86% vs. transitioning 91%, p = 0.44).

Conclusion: Adults retained in care receiving WHO-recommended first-line dolutegravir-based ART achieved viral suppression rates of ≥ 95% up to two years. These findings align with the UNAIDS 95% suppression target and reinforce the role of dolutegravir-based regimens in ending HIV as a public health threat.

Trial registration: CRD42024557769.

Dolutegravir is a preferred antiretroviral drug given its high resistance barrier and efficacy; however, reports from sub-Saharan Africa indicate increased hyperglycemia rates among individuals living with HIV on dolutegravir. Potential mechanisms include mitochondrial dysfunction from previous exposure to NRTIs like stavudine and zidovudine, which causes mitochondrial toxicity and predisposes patients to hyperglycemia upon switching to dolutegravir; magnesium chelation, which is borrowed from dolutegravir's mode of action (dolutegravir inhibits the action of integrase by chelation of magnesium required as a cofactor by the HIV enzyme); and chronic inflammation, with elevated pro-inflammatory markers like IL-6, CRP, and TNF-α contributing to insulin resistance. The narrative review highlights variability in hyperglycemia among patients, influenced by genetics, lifestyle, and prior antiretroviral therapy. The exact nature of dolutegravir-associated hyperglycemia, whether due to insulin resistance or reduced insulin release, remains unclear, although insulin resistance is significant.

Sub-Saharan Africa (SSA) remains at the epicentre of the global HIV epidemic and faces a decisive moment in its journey toward achieving the UNAIDS 95-95-95 targets. This review aims to provide a comprehensive overview of the progress toward these targets in SSA, identifying key challenges, barriers to viral load suppression, and potential strategies to improve treatment adherence and health outcomes. These goals-ensuring that 95% of people living with HIV know their status, 95% of those diagnosed are receiving treatment, and 95% of those receiving treatment achieve VLS-represent a bold vision to end HIV as a public health threat by 2030. However, across the region, progress is threatened by persistent structural barriers, entrenched stigma, health system weaknesses, and recent global funding disruptions, including the 2025 freeze on U.S. foreign aid. This review explores the multifaceted obstacles that continue to hinder the HIV response in SSA, from testing gaps to challenges in care retention and VLS, particularly among vulnerable populations. It further examines the potential consequences of funding cuts for health system resilience and epidemic control. Emphasising the need for equity-driven, locally adapted, and innovative strategies-such as community-based service delivery, digital health tools, long-acting therapies, and integrated care models-this article argues for renewed political commitment, sustainable financing, and stronger local and global partnerships. When setbacks loom large, this piece calls for urgent, coordinated action to protect progress, address persistent inequities, and secure a future where epidemic control is truly within reach.

Background: This retrospective observational study evaluated the clinical use and treatment outcomes in virologically suppressed people with HIV (PWH) switching to either bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based regimens (single- and multi-tablet formulations (STR and MTR)).

Methods: We analyzed electronic medical and dispensing records from Trio Health HIV Research Network for treatment-experienced PWH ≥ 18 years suppressed (viral load [VL] < 200 copies/mL) at switch to B/F/TAF, DTG STR (DTG/3TC, DTG/RPV, DTG/3TC/ABC) or most common DTG MTRs with VL at 12 months (+/-3) since switch between April 2019 and December 2024. Univariate comparisons: chi-square or t-test; characteristics associated with virologic suppression at 12 months: multivariable logistic regression [LR], controlling for age, gender, race, baseline CD4 count, regimen, and adherence (proportion days covered [PDC] ≥ 80%).

Results: Of 3141 PWH, 66% switched to B/F/TAF, 27% to DTG STR, and 7% to DTG MTRs. Baseline characteristics differed significantly between groups: B/F/TAF group had a higher proportion of males (81% vs. 67% DTG MTR) and Black individuals (40% vs. 31% DTG STR), while the DTG STR and MTR groups had higher proportions of PWH with cardiovascular disease (35% and 39% respectively vs. 32% on B/F/TAF) and eGFR < 60 mL/min/1.73 m² (18% and 22% respectively vs. 8% on B/F/TAF). At 12 months post switch, proportion of individuals with PDC ≥ 80% was higher in the DTG STR group (76%) compared to DTG MTR (67%) and B/F/TAF (69%) with similar virologic suppression across groups (98%, 98%, and 97% respectively). In multivariable LR, there was an association of White race, PDC ≥ 80%, and CD4 ≥ 200 cells/mm³ with greater probability of suppression at 12 months.

Conclusions: Despite differences in baseline characteristics and regimen adherence between individuals switched to B/F/TAF, DTG STRs, and MTRs, both B/F/TAF and DTG-based regimens were associated with high rates of virologic suppression. This data strongly supports the inclusion of these simple and safe regimens as switch options in virologically suppressed PWH. Baseline differences in patient demographics and characteristics may have impacted the adherence on B/F/TAF compared to DTG STR, however virologic outcomes were preserved, demonstrating the forgiveness of B/F/TAF in populations potentially facing adherence challenges.

Background: Progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) is a high-mortality disease among patients with AIDS. It is caused by infection with the John Cunningham virus (JCV). Currently, there are no specific antiviral treatments targeting JCV. Thus, immune reconstitution remains the primary therapeutic approach.

Case presentation: A 29-year-old male patient diagnosed with AIDS presented for medical evaluation after two months of antiretroviral therapy (ART), reporting symptoms of dizziness and headache. The detection of JC virus was confirmed in cerebrospinal fluid (CSF) through metagenomic next-generation sequencing (mNGS) analysis. Plain and enhanced cranial MRI scans revealed diffusely distributed nodular and patchy enhancement shadows within the brain parenchyma, consistent with a diagnosis of PML-IRIS. Given that glucocorticoids and PD-1 inhibitors may possess higher toxicity profiles and side effects compared to intravenous immunoglobulin (IVIG), which has been shown to restore immune function while causing fewer adverse reactions rapidly, a five-day regimen of intravenous IVIG infusion was administered in conjunction with continuous ART. Following this intervention, the patient showed significant clinical improvement, including reduced dizziness and headache, and improved neurological function.

Conclusions: The administration of IVIG alone may be considered an effective immunologic reconstitution strategy in treating early stages of PML-IRIS associated with AIDS, despite the complexity of the disease. This approach could be attributed to direct anti-JCV effects, neutralization of toxins, inhibition of inflammatory cytokine release, and its relatively tolerable safety profile. This case report aims to serve as a reference for clinical practitioners regarding the use of standalone IVIG therapy for HIV-related early PML-IRIS management; however, further investigation is warranted to determine its efficacy in cases where PML-IRIS has been detected at later stages.

Introduction: Hypoalbuminemia is linked to an earlier onset of acquired immune deficiency syndrome and increased mortality in patients living with HIV infection. Serum albumin is therefore an independent factor for the prediction of disease progression and mortality in People Living With HIV.

Methods: This was a cross-sectional study conducted at Lira Regional Referral Hospital in northern Uganda that targeted HIV-positive outpatients attending the ART clinic with a sample size of 373 patients. Data were collected through structured interviews and laboratory tests in which the serum albumin concentration, viral load, and CD4 count were measured.

Results: The prevalence of hypoalbuminemia was 19.6% (73/373). A moderate positive correlation was observed between the serum albumin concentration and the CD4 count (rs = 0.43, p < 0.001). Patients with no formal education [AOR = 2.03, 95%CI = 1.69-2.07, P = 0.03] were 2.03 times more likely to have hypoalbuminemia than those who had a tertiary/university education level. The odds of having hypoalbuminemia [AOR = 2.17, CI = 1.80-3.06, P = 0.02] were 2.17 higher among HIV-infected patients who were naïve ART than among those who were on ART. Additionally, the odds of having hypoalbuminemia [AOR = 2.91, CI = 2.13-3.66, P = 0.01] were 2.91 higher among HIV-infected patients who were in stage four than among those who were in stage 1.

Conclusion: Hypoalbuminemia prevalence was high in PLWHIV, and a moderate positive correlation was found between the serum albumin level and the CD4 cell count. Lower education level, not being ART, and advanced HIV disease were independently associated with hypoalbuminemia.

Background: Many people with HIV experience considerable barriers to accessing HIV clinic services. Options that would permit blood sampling that preclude the need for in-clinic visits and increase privacy would aid in overcoming many of the obstacles that hinder receiving adequate HIV care.

Methods: In Project Home-MaDE, 57 participants were evaluated for their ability to collect fingerstick blood (minimum 250 µL) in Microtainer tubes (MCT), then package and overnight mail specimens following kit instructions without assistance. Specimens were required to arrive at the laboratory within four days of collection. Plasma viral loads obtained from mailed blood were compared to matched venipuncture samples collected on the same day. For fingerstick-derived plasma, the limit of quantitation was 210 copies/mL, a benchmark relevant for Undetectable = Untransmissible prevention. A non-reactive or below-quantifiable result reflected viral suppression. Self-collected dried blood spots which have historically been used for remote blood sampling were likewise evaluated.

Results: Forty-seven (82%) participants had acceptable MCT samples for testing. Ten specimens were rejected either for excessive time and temperature (n = 1) or insufficient sample volume (n = 9). Of the 34 participants who initially experienced difficulty in obtaining sufficient sample 29 elected to retry and 24 were successful. All 46 acceptable MCT plasmas tested provided accurate results as compared to the suppression levels in their matched conventional venipuncture viral loads.

Conclusion: Under a rigorous protocol, plasma from mailed, self-collected fingersticks by untrained individuals were suitable for remote viral suppression monitoring. This evaluation, however, was limited to temperatures and courier service in the U.S. Approved testing options for self-collected samples may support HIV telemedicine and empower persons to overcome barriers to care services.