Current HIV Research - Volume 22, Issue 5, 2024

COVID-19 has inevitably influenced health systems. HIV testing rates have been reduced, and access to antiretroviral treatment has been scaled down. We evaluated the impact of COVID-19 on the management of people living with HIV (PLWH) in Türkiye.

We conducted a cross-sectional study in three tertiary care hospitals. We compared the baseline characteristics at the first visit and viral suppression rates at the 24th week of new HIV diagnoses during the pandemic with those during the previous two years. To observe the effect of the pandemic on people living with HIV who were already in care, we compared the metabolic and clinical parameters like weight, blood pressure, blood lipid levels, fasting glucose levels, and liver and renal function tests, of the same people before and during the pandemic.

The first group included 380 cases (127 diagnosed during the pandemic and 253 diagnosed during the previous year). The demographic characteristics were similar. The newly diagnosed PLWH during the pandemic had significantly higher baseline HIV RNA levels (p=0.005), a lower number of clinical visits (p=0.0005), and a lower number of cases with undetectable viral loads at 24 weeks of treatment (p=0.0005) than those diagnosed during the pre-pandemic period.

The second group included 261 individuals with a mean follow-up duration of 24.7 (SD± 3.5; min- max 12-144) months. The comparison of laboratory parameters revealed that in the post-pandemic period, virologic suppression was maintained at 90.1%, body mass index (p=0,0001), total cholesterol (p=0,0001), and LDL levels (p=0,0001) increased significantly, and creatinine levels decreased significantly (p=0,0001).

Our study showed that COVID-19 deteriorated the HIV management of PLHIV. Strengthening the medical infrastructure of basic services for PLWH is critical for future crises.

In the Hebei province, Human Immunodeficiency Virus type one (HIV-1) recombinant strains of subtypes B, C, and CRF01_AE are emerging very rapidly and diversely.

In order to confirm the characteristics of novel recombination forms, we aimed to analyze HIV-1 Near-full-length Genome sequences (NFLGs) obtained from three Men who have Sex with Men (MSM) in this study.

Phylogenetic trees were constructed and breakpoints analysis were performed based on the NFLGs and each gene fragment to examine the gene recombination patterns of three new HIV-1 NFLGs.

HIV-1 subtypes CRF01_AE and B were combined to generate the recombinant structures of the NFLGs 610 and 687. CRF01_AE, B, and C were combined to generate the recombinant structures of the NFLG 825. According to the NFLG phylogenetic tree, the NFLG 825 clustered with CRF65_cpx and the NFLGs 610 and 687 clustered with CRF68_01B. The recombination breakpoints analysis revealed that the recombination pattern of the NFLGs 610 and 687 was the insertion of subtype B fragment into the CRF01_AE backbone. Subregions I, II, and III were derived from CRF01_AE, subtype B, and CRF01_AE, respectively. The recombination pattern of the NFLG 825 contained ten fragments of subtypes CRF01_AE, C, and B. Finally, the above factors were formed using phylogenetic trees and breakpoints analysis, which were combined to get two CRF68_01B forms and one CRF65_cpx form.

Our findings have suggested that it is crucial to keep an eye on the genetic diversity of HIV-1 in Hebei province.

HIV-associated pulmonary arterial hypertension (HIV-PAH), a rare and fatal condition within the pulmonary arterial hypertension spectrum, is linked to HIV infection. While ferroptosis, an iron-dependent cell death form, is implicated in various lung diseases, its role in HIV-PAH development remains unclear.

Leveraging Gene Expression Omnibus data, we identified differentially expressed genes (DEGs) in pulmonary arterial smooth muscle cells, including HIV-related DEGs (HIV-DEGs) and ferroptosis-related HIV-DEGs (FR-HIV-DEGs). PPI network analysis of FR-HIV-DEGs using CytoHubba in Cytoscape identified hub genes. We conducted functional and pathway enrichment analyses for FR-HIV-DEGs, HIV-DEGs, and hub genes. Diagnostic value assessment of hub genes utilized ROC curve analysis. Key genes were further screened, and external validation was performed. Additionally, we predicted a potential ceRNA regulatory network for key genes.

1372 DEGs were found, of which 228 were HIV-DEGs, and 20 were FR-HIV-DEGs. TP53, IL6, PTGS2, IL1B (downregulated), and PPARG (upregulated) were the five hub genes that were screened. TP53, IL6, and IL1B act as ferroptosis drivers, PTGS2 as a ferroptosis marker, and PPARG as a ferroptosis inhibitor. Enrichment analysis indicated biological processes enriched in “response to oxidative stress” and pathways enriched in “human cytomegalovirus infection.” Key genes IL6 and PTGS2 exhibited strong predictive value via ROC curve analysis and external validation. The predicted ceRNA regulatory network identified miRNAs (has-mir-335-5p, has-mir-124-3p) targeting key genes and lncRNAs (XIST, NEAT1) targeting these miRNAs.

This study advances our understanding of potential mechanisms in HIV-PAH pathogenesis, emphasizing the involvement of ferroptosis. The findings offer valuable insights for future research in HIV-PAH.

People with the human immunodeficiency virus (PWH) who were diagnosed long ago are more prone to age-related conditions and comorbidities than the general population. We hypothesized that older PWH have endocrine abnormalities that may influence the patient’s health status.

Mean hormonal values across the thyrotropic, somatotropic, corticotropic, and gonadal axis, and percentage of subjects with abnormal values, were compared between PWH aged ≥50 years (n=30) and people without HIV (n=30) (Over50 cohort). Clinical factors were also analyzed as independent variables.

PWH had a higher prevalence of comorbidities (36.67% PWH and 20.69% controls had ≥3 comorbidities). Male PWH exhibited lower estradiol levels than male controls (29.75±7.68 pg/mL vs. 35.45 ± 10.04 pg/mL; p = 0.0041). Abnormal concentrations of testosterone were found in 35% of male PWH compared to 55% of male controls (mostly above reference values). Cortisol levels were significantly lower among PWH (9.97 ± 4.33 µg/dL vs. 13.56 ± 3.39 µg/dL; p = 0.002); 16.6% of PWH exhibited abnormally low levels (<5 μg/dL), compared to 0% of controls, and 3 PWH met criteria for a definitive diagnosis of adrenal insufficiency (<3.6 μg/dL). For the somatotropic axis, growth hormone (GH) levels were significantly lower in male PWH than in controls (p = 0.0394). No significant differences were found in relation to the thyroid axis.

Hormones are generally similar between the chronic PWH who are receiving ART treatment and the general control population, except for cortisol in both sexes and testosterone and estradiol in men. Some special attention should be given to cortisol in PWH due to a presumably higher risk of adrenal complications.

Diagnosis for HIV in infants is hard to determine, particularly in limited-resource areas. A delay in the diagnosis of HIV-infected infants will lead to high morbidity and mortality. The purpose of this project is to construct a model of an HIV-positive infant and develop a useful and practical scoring system to estimate the likelihood of mother-to-child transmission that can be applied in the field.

A cross-sectional study on 100 subjects through medical records of infants born to HIV-infected mothers was conducted at four hospitals and one community health center. Several models of risk prediction scores of HIV-infected infants were then made. Furthermore, the performed validation was performed on 20 subjects of infants born to mothers with HIV in three hospitals by comparing the scoring system and the result of the PCR RNA examination performed at the age of 6 weeks old.

The risk of HIV-infected infants was higher in mothers who did not receive ARV through PMTCT programs (OR 33.6; 95% CI 4.0 to 282.2), pulmonary TB infection (OR 5.1; IK95% 1.6 to 16.0) and vaginal delivery (OR 9.2; IK95 2.2 to 38.0%). Two models can predict the occurrence of infected HIV infants effectively. Model 1 consists of maternal age, maternal ARVs, lung TB infection, gestational age, mode of delivery, and sex of the infants with sensitivity and specificity of 78.9% and 70.8% (AUC=0.817 [95% CI 0.709 to 0.926]) and likelihood ratio score of 4. Model 2 consists of ARVs to the mother, pulmonary TB infection, and mode of delivery with sensitivity and specificity of 73.7% and 86.1%; AUC value of 0.812 (95% CI 0.687 to 0.938) and likelihood ratio of 5. External Validation gave similar results to the Model 2 scoring system with PCR RNA.

The prediction score of HIV-infected infants in Model 2 can be used in newborns of HIV-positive mothers as an effective and practical risk screening tool for HIV-infected infants before the gold standard examination by PCR.

Virological failure (VF) among children remains concerning, with high risks of HIV drug resistance (HIVDR) emergence and increased disease progression. Therefore, monitoring of viral non-suppression and emerging HIVDR is crucial, especially in the frame of sociopolitical unrest.

The study sought to determine the prevalence of VF and evaluate the acquired HIVDR and viral genetic diversity among children in the Northwest region of Cameroon during the ongoing sociopolitical crisis.

A cross-sectional facility-based study was conducted among HIV-infected children aged ≤18 years, receiving antiretroviral therapy (ART) in urban and rural settings of Northwest Cameroon, from November 2017 through May 2018. Viral load (VL) was done using the Abbott m2000RealTime. Unsuppressed VL was defined as viral load ≥1,000 copies/ml. HIVDR testing was performed by sequencing of HIV-1 protease-reverse transcriptase at the Chantal Biya International Reference Center (CIRCB) using an in-house protocol. Drug resistance mutations (DRM) were interpreted using Stanford HIVdbv8.5 and phylogeny using MEGAv.6. Data were compared between urban and rural areas with p<0.05 considered statistically significant.

A total of 363 children were recruited, average age of 12 years (urban) and 8 years (rural). VL coverage was 100% in the urban setting and 77% in the rural setting. Overall, VF was 40.5% (39% [130/332] in the urban setting and 41% (13/31) in the rural setting; p=0.45). Overall, viral undetectability (defined as VL<40 copies/ml) was 45.5% (46% (urban) and 45% (rural); p=0.47). Among those experiencing confirmed virological failure and who were successfully sequenced (n=35), the overall rate of HIVDR was 100% (35/35). By drug class, HIVDR rates were 97.1% (34/35) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 97.1% (34/35) for NRTIs and 17.1% (6/35) for protease inhibitors (22.7% (5/22) in the urban setting and 7.7% [1/13] in the rural setting). CRF02_AG was the most prevalent viral clade (75%), followed by other recombinants (09_cpx, 11_cpx, 13_cpx, 22_01A1, 37_cpx) and pure subtypes (A1, F2, G, H).

In this population of children and adolescents living with HIV in a context of socio-political instability in the North-West region of Cameroon, rates of viral non-suppression are high, and accompanied by HIVDR selection. Our findings suggest the need for a more differentiated care of these CAHIV, especially those in these regions faced with significant socio-economic and health impacts due to the ongoing crisis.