AIDS Research and Therapy最新文献

Background: Kenya is among the six high-burden HIV/AIDS countries in Africa, with approximately 1.3 million people living with HIV as of 2024. This includes an estimated 62,000 children aged 0-14 years. Mother‒child transmission (MTCT) of HIV during pregnancy, labour, delivery, or breastfeeding significantly contributes to new infections among children. In the absence of prevention interventions, MTCT rates range from 15 to 45% but can be reduced to less than 5% with antiretroviral therapy. Women in Kenya have a higher HIV prevalence rate than men do, with 5.2% for women and 4.5% for men. Geographic disparities in HIV prevalence exist within the country and are influenced by cultural practices, sexual behavior, and economic activities. Despite efforts to increase knowledge about HIV prevention, gaps remain, particularly among young people, rural populations, and those with lower educational levels. The Kenya Demographic and Health Survey (KDHS) highlights significant knowledge gaps among HIV-positive pregnant women regarding MTCT and the benefits of antiretroviral drugs. Challenges in preventing MTCT in Kenya include limited knowledge, a lack of adherence to the PMTCT cascade, and barriers such as stigma, weak health systems, and socioeconomic factors.

Methods: This study aims to determine the HIV knowledge and challenges faced by HIV-positive pregnant women in western Kenya regarding adherence to PMTCT protocols and to make recommendations to curb these challenges. Using a mixed-methods approach, including a survey and focus group discussions (FGDs), the study targeted HIV-positive pregnant women at Homa Bay County Referral and Teaching Hospital. Convenience sampling was used to select participants.

Results: Key findings indicate that while awareness of MTCT exists, misconceptions and knowledge gaps persist. Themes from FGDs include viewing HIV as a curse, negative feelings about HIV status, fear of disclosure, comparisons with other diseases, and the importance of self-encouragement.

Conclusion: The study concludes that HIV-positive pregnant women in western Kenya face significant challenges in adhering to PMTCT protocols because of persistent myths, stigma, and socioeconomic barriers. Recommendations include enhancing education and support systems to improve adherence to PMTCT and reduce MTCT rates.

Background: While non-disclosure of HIV status may protect people living with HIV (PLWH) against stigma, discrimination, and violence, disclosure may facilitate access to social support and improve treatment adherence. This study examined factors associated with non-disclosure among recently-diagnosed PLWH at IeDEA study sites in Cameroon.

Methods: We conducted a cross-sectional study of adults ≥ 19 years newly enrolling in HIV care at three Cameroon hospitals from January 2016 to June 2023 with recent (< 1 year) diagnoses and no evidence of prior HIV care. We used logistic regression to identify factors associated with non-disclosure of HIV status at the time of enrolment.

Results: Among 2880 participants, the overall prevalence of HIV status non-disclosure at enrolment was 34.4%, ranging from 48.0% among those enrolling on the day of diagnosis to 18.7% among those enrolling > 30 days after diagnosis. Men and single participants had higher odds of non-disclosure compared with women (aOR: 1.68; 95% CI 1.38, 2.04) and those who were married/living with a partner (aOR: 1.66; 95% CI 1.36, 2.02). Those with early-stage HIV disease (WHO Stage 1 or 2 or CD4 ≥ 200 cells/mm³) also had higher odds of non-disclosure (aOR: 1.48; 95% CI 1.20, 1.83) compared with participants with advanced-stage disease.

Conclusion: Among those diagnosed with HIV within 1 year prior to enrolment, men, single/unmarried people, and those with early-stage HIV disease were less likely to disclose their status. Further research on barriers to status disclosure among these groups is needed to guide disclosure support and counselling interventions.

This study examines the prevalence of Human immunodeficiency virus (HIV) in Mizoram, Northeast India, with a focus on age-group transmission routes and gender-specific prevalence. According to data from the ART Plus Centre at Civil Hospital Aizawl (January-December 2023), men were more likely to be infected with HIV, with the 26-35 age group being the most affected. Heterosexual transmission and intravenous drug use (IDU) were shown to be the most common modes of transmission. Gender and age variations were identified by statistical analysis using SPSS^® (V 27.0), highlighting the need for focused interventions. To effectively combat the HIV epidemic in this area, gender-specific policies, harm reduction strategies, and stigma reduction measures are essential.

Background: The HIV epidemic in Africa is still a serious public health concern, particularly for children who are more vulnerable to its negative consequences. Various studies carried out in different African nations have shown associations between these variables and increased mortality risk in children receiving antiretroviral therapy. However, the magnitude and consistency of these effects across different settings in Africa remain unclear, with a few studies reporting nonsignificant effects of advanced disease stage and immunological factors on mortality. This review is the first to provide a thorough analysis of the determinants of HIV-related mortality in children.

Methods: This review followed the PRISMA guidelines, and relevant studies were obtained from the PubMed, CINAHL, EMBASE, and Google Scholar databases. Study selection, data extraction, and quality evaluation were carried out separately by two reviewers. A heterogeneity-based meta-analysis was conducted using random effect models. A sub group analysis was done based on age group and country.

Results: A total of 36 studies involving 198,957 study participants were included in the review. Advanced disease stage (WHO III/IV) (HR 3.45; 95% CI 2.17-5.48), TB coinfection (HR 2.12; 95% CI 1.53-2.92), opportunistic infections (HR 2.04; 95% CI 1.59-2.62), immunosuppression (HR 2.50; 95% CI 2.01-3.11), and poor medication adherence (HR 3.36; 95% CI 2.10-5.38) and lack of cotrimoxazole use (HR 2.2; 95% CI 1.14-4.26) were significantly associated with a greater risk of HIV-related mortality.

Conclusion: This review revealed key clinical, immunological, and treatment-related predictors of HIV-related mortality in children in Africa, including advanced disease stage, TB co-infection, immunosuppression, poor adherence, and lack of cotrimoxazole use. To reduce HIV-related child mortality in Africa, health policies should strengthen pediatric HIV care through context-specific service delivery. This includes early identification of advanced disease, management of opportunistic infections, access to cotrimoxazole prophylaxis, and age-appropriate adherence support, especially in under-resourced settings.

HIV-1 drug resistance (HIVDR) surveillance among individuals failing antiretroviral therapy (ART) is essential to selecting optimal ART-combinations for use in a public health approach in low-middle-income countries (LMICs) where routine HIVDR-testing remains limited. This study describes patterns of acquired drug resistance (ADR) and potentially active drugs for subsequent ART regimens in individuals failing treatment in Cameroon. We conducted a cross-sectional, laboratory-based sentinel study among ART-failing individuals from October 2022 through April 2023 at the "Chantal Biya" International Reference Centre, Yaoundé-Cameroon. Individual samples with confirmed virological failure were sequenced in HIV-1 protease and reverse-transcriptase genes using Sanger sequencing and analysed using Stanford HIVdatabase.v.9.4. Overall, 203 individuals were enrolled, median [IQR] age 37 [16-47] years with 58.1% (118/203) being female. Median [IQR] duration on ART was 10 [6.9-13.3] years, with majority failing second-line (78.7%; 160/203). HIVDR rate was 85.3% (29/34) and 88.1% (140/160) in those failing first-line and second-line therapy respectively (p = 0.7). NNRTI, NRTI and PI/r resistance in individuals failing first-line ART was 85.3% (9/34), 82.4% (28/34) and 2.9% (1/34) respectively. In second-line failure, NNRTI, NRTI and PI/r resistance was 86.8% (138/160), 84.9% (135/160) and 47.17% (75/160) respectively. NRTI-NNRTI dual-class-resistance was 82.4% (28/34) after first-line and 84.3% (134/160) after second-line (p = 0.842), while triple-class-resistance was 2.9% (1/34) after first-line and 45.3% (72/160) after second-line (p < 0.0001). After first-line, TDF and AZT maintained potential efficacy in respectively 53.4% (18/34) and 46.7% (16/34) of individuals, while 46.7% (16/34) had cross-resistance to second-generation NNRTI. After second-line failure, 95.6% (153/160) maintained DRV/r efficacy, as compared to 67.3% for ATV/r (p < 0.0002), 73.9% for LPV/r (p < 0.0002), and 34.7% (56/160) for RPV/DOR. Among ART-failing individuals in Cameroon, levels of ADR are high with significant levels of cross-resistance to second-generation NNRTI, hence potentially jeopardizing the use of long-acting cabotegravir/rilpivirine. Furthermore, HIVDR testing could be considered from first-line failure in such settings, but chiefly following second-line failure wherein triple-class-resistance is common and calls for novel antiretrovirals in similar LMICs.

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.