Current HIV Research - Volume 20, Issue 3, 2022

Background: Small experimental studies suggest that PTH-secretion following hypocalcemia might be blunted in people living with HIV. Objective: The aim of the study was to estimate the frequency of inadequately low concentrations of parathyroid hormone in the presence of hypocalcemia in people living with HIV. Methods: This was a retrospective study that was conducted among PLWH enrolled in the ongoing ArcHIV study between 2016 and 2017. PLWH with routine measurements for both calcium and parathyroid hormone levels were included in this analysis. The proportion of patients with a combination of low levels of both calcium and parathyroid hormone was the primary endpoint of this analysis. Result: 496 PLWH were included (mean age 47.1 (± 10.2) years, 393 (79.2 %) men). In 14 (2.8 %) PLWH, low calcium levels with low levels of PTH were observed in the assessment conducted in both years. Undergoing a tenofovir disoproxil-containing treatment in both years was the only explanatory variable significantly associated with inadequately low levels of PTH in the presence of hypocalcemia in both years (OR 4.3 [CI95: 1.4; 16.0]). Conclusion: The combination of low levels of both calcium and PTH was found more frequent in our study sample when compared to what is expected from the general population. Interestingly, undergoing a tenofovir disoproxil-containing therapy was associated with this combination throughout both the years.

Background: Underutilization of HIV pre-exposure prophylaxis (PrEP) in the Southern United States (US) is well-documented. Urgent care (UC) centers are positioned as communityfacing access points to PrEP, but the feasibility of integrating PrEP services into this setting is unclear. We conducted a survey of UC clinicians in the Southern US to better understand their perceptions of the feasibility of providing PrEP in their practice setting. Objective: The study aims to determine the feasibility and acceptability of providing PrEP services in the UC setting through a cross-sectional survey of UC clinicians. Methods: We conducted a 48-item cross-sectional survey of UC clinicians in the Southern US, between July and September 2020. The survey was distributed through the Urgent Care Association (UCA) and American Academy of Urgent Care Medicine (AAUCM) professional listservs as well as directly to publicly listed e-mail addresses. Results: Eighty-two clinicians responded to the survey. Most clinicians had familiarity with PrEP (97%). All respondents rated PrEP as an effective way to prevent HIV. However, less than half felt UC facilities were an appropriate place to prescribe PrEP. Few respondents (8%) expressed doubts that expansion of PrEP access would decrease the incidence of HIV in their community. Conclusion: These findings show UC clinicians are familiar with PrEP, and many believe it would benefit their patients; however, provider opinions on the appropriateness of providing PrEP in the UC setting differ. Further studies on PrEP implementation in UC centers are needed.

Background: Typically, genotypic resistance testing is recommended at the start of antiretroviral therapy and is even mandatory in cases of virologic failure. The material of choice is plasma viral RNA. However, in patients with low viremia (viral load < 500 copies/ml), resistance testing by population-based sequencing is very difficult. Objective: Therefore, we aimed to investigate whether next generation sequencing (NGS) from proviral DNA and RNA could be an alternative. Material and Methods: EDTA blood samples (n = 36) from routine clinical viral load testing were used for the study. Viral loads ranged from 96 to 390,000 copies/mL, with 100% of samples having low viremia. Distribution of subtypes; A (n = 2), B (n = 16), C (n = 4), D (n = 2), G (1), CRF02 AG (n = 5), CRF01 AE (n = 5), undefined/mixed (n = 4). The extracted consensus sequences were uploaded to the Stanford HIV Drug Resistance Data Base and Geno2pheno for online analysis of drug resistance mutations and resistance factors. Results: A total of 2476 variants or drug resistance mutations (DRMs) were detected with Sanger sequencing, compared with 2892 variants with NGS. An average of 822/1008 variants were identified in plasma viral RNA by Sanger or NGS sequencing, 834/956 in cellular viral RNA, and 820/928 in cellular viral DNA. Conclusion: Both methods are well suited for the detection of HIV substitutions or drug resistance mutations. Our results suggest that cellular RNA or cellular viral DNA is an informative alternative to plasma viral RNA for variant detection in patients with low viremia, as shown by the high correlation of variants in the different viral pools. We show that by using UDS, a plus of two DRMs per patient becomes visible, which can make a big difference in the assessment of the expected resistance behavior of the virus.

Introduction: This preliminary real-world study (RWS) was designed to evaluate the antiviral efficacy, safety, and feasibility of the 2-drug regimen (2DR), dolutegravir plus lamivudine as the initial antiretroviral therapy (ART) among antiretroviral (ARV)-naïve adults with HIV-1 in West China. Methods: This RWS included the treatment of treatment-naïve adults applying 2DR of dolutegravir 50 mg once daily (QD) plus lamivudine 300mg QD with negative HBsAg from one single center of People’s Hospital of Chongqing Banan District in West China. Viral load (VL), CD4+ T-cell count, and laboratory indicators were collected at baseline; weeks 4, 12, and 24, and thereafter every 24 weeks up to 144 weeks. The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 24. Results: A total of 54 ART-naïve patients were treated with the 2-drug regimen of DTG plus 3TC and were enrolled in this study since April 1st, 2020. Twenty-one patients received 24-week VL tests at screening as required by inclusion criteria. Median HIV-1 RNA at entry was 95,700 copies/ mL (interquartile range (IQR): 28,300-310,000) and the median baseline CD4+ cell count was 249 per cubic millimetre(IQR: 118-310). At week 24, 15 (71.4%) of 21 participants achieved virological success, defined as HIV-1 RNA < 50 copies/mL, while 10 (90.9%) of 11 participants with a baseline HIV-1 RNA < 100,000 copies/mL achieved virological success compared with 5 (50%) of 10 participants with a baseline HIV-1 RNA ≥100,000 copies/mL [Relative Risk (RR) 1.818; 95% CI 1.018-1.927]. In participants with CD4+ cell counts ≥ 200 cells/mm3, 9 (75%) of 12 participants achieved virological success compared with 6 (66.7%) of 9 participants with baseline CD4+ cell count < 200 cells/mm3 achieved it (RR 1.124; 95% CI 0.641-1.970). No major tolerability/toxicity issues were observed. Conclusion: This real-world study suggested that the 2-drug regimen of DTG plus 3TC could be considered as an alternative for ART-naïve patients in West China, especially with HIV-1 RNA less than 100,000 copies/mL at baseline, regarding the limits of viral load test frequency and the absence of HIV genotypic testing of viral resistance.

Background: Increasing the sensitivity and availability of liquid chromatography tandem mass spectrometry (LC-MS/MS) devices may provide advantages in terms of revealing the changes in metabolic pathways in HIV-positive patients and elucidating the physiopathology. Introduction: The aim of this study was to determine the difference in amino acid levels between HIV-positive patients and healthy individuals by using LC-MS / MS and investigate its relationship with HIV infection. Material and Methods: Concentrations of 36 different amino acids and their derivatives were measured and compared in venous plasma samples from 24 HIV-positive patients and 24 healthy individuals by using the LC-MS/MS method (Shimadzu North America, Columbia, MD, USA). Results: HIV-positive subjects had significantly lower alanine, 1-methyl-L-histidine, valine, aspartate, cysteine, cystine, methionine, lysine, glutamine, imino acid, tyrosine, tryptophan, threonine, sarcosine, and argininosuccinic acid and significantly higher 3-methyl-L -histidine, asparagine, glutamate, and carnosine levels as compared to healthy controls. No significant differences were detected in other amino acids. Conclusion: The significant differences in amino acid profile between HIV-positive and healthy subjects may represent an auxiliary biomarker of cellular damage in asymptomatic HIV-positive patients that may be examined in more detail in further studies. It may also provide guidance for symptomatic cases in terms of the association between symptoms, clinical manifestations, and deficiency or excess of certain amino acids in the context of the complete metabolomics record of HIVpositive patients.

Aims: The COVID-19 pandemic has substantially changed lives and presented several barriers to health services. HIV care continuum needs a high rate of diagnosis, effective treatment, and sustained suppression of viral replication. The COVID-19 pandemic has affected these three steps of HIV care. This study investigated the characteristics of newly diagnosed patients living with HIV/AIDS (PLWH) during the COVID pandemic and compared them with those before the pandemic. Methods: All newly diagnosed patients in three HIV healthcare centers, in Istanbul, Turkey, were included in the study. The pandemic period included April 1, 2020, to April 1, 2021, and the prepandemic period included March 1, 2019, to March 1, 2020. Results: 756 patients were diagnosed with HIV/AIDS. In the pandemic period, this figure was 58% less: 315. Patients in the pre-pandemic and pandemic period had comparable age and gender distributions. PLWH diagnosed in the pandemic period had higher rates of low CD4 cells: low CD4 (<350 cells /mm3) was measured in 243 (36.4%) patients in the pre-pandemic period, while it was done in 126 (47.9%) in the pandemic period (p<0.01). Also, the distribution of CD4 cells was significantly different between periods: In the pandemic period, CD4 cell distribution significantly skewed to lower CD4 categories. Symptomatic patient rates and AIDS-defining disorder rates among symptomatic patients were comparable. Viral loads were not significantly different in the two periods. Conclusion: A low number of newly diagnosed PLWH can be explained by less HIV testing, less admission to health care, or an actual decrease of HIV prevalence during the pandemic. Sexual behaviors may have changed during the COVID-19 pandemic, leading to HIV transmission restriction. Lower CD4 counts among the newly diagnosed PLWH suggest that admittance to health care is late and a significant portion of PLWH remain undiagnosed.

Background: The data of the impact of tenofovir (TDF) on kidney damage in Chinese HIV-1 infected patients are limited. Objective: The study aims to evaluate the incidence and risk factors of stage 3 chronic kidney disease (CKD) and rapid kidney function decline (RKFD) among Chinese HIV-1 infected patients starting with a TDF-based regimen. Methods: We enrolled 797 TDF-initiated HIV-1-infected patients in a Chinese cohort. Kidney dysfunctions were defined as stage 3 CKD (eGFR < 60 mL/min/1.73 m² during follow-up) and RKFD (eGFR decline > 10 mL/min/1.73 m²/year). A linear mixed-effects model was used to quantify the average eGFR change per 48 weeks. A generalized estimating equation regression analysis was conducted to determine the risk factors associated with renal dysfunction. The method of multiple imputations was used to reduce the bias caused by missing data. Results: In this retrospective study, 14 (2%) patients experienced stage 3 CKD, and 272 (34%) individuals experienced RKFD during a median of 26 (IQR, 4-78; maximum 325) weeks follow-up period. The mean loss in eGFR per 48 weeks increased consistently over time, from -2.59 mL/min/1.73 m² before 48 weeks to -17.61 mL/min/1.73 m² after 288 weeks. For every 10 mL/min/1.73 m² increase of eGFR, the risk of RKFD increased by 29% (95%CI: 18%, 40%). Each 10 years older and every 10 mL/min/1.73 m2 higher in baseline eGFR, the risk of stage 3 CKD increased to 1.56 (95% CI: 1.00, 2.43) and decreased by 65% (95% CI: 48%, 76%), respectively. Anemia and higher viral load were significantly associated with RKFD. The results were robust across a range of multiple imputation analyses. Conclusion: TDF-associated CKD is rare in HIV-1 infected Chinese adults. Longer TDF-exposed patients are more likely to have renal dysfunction, especially those with older age, anemia, lower baseline eGFR, and higher viral load.

Background: We report NP, clinical and laboratory changes in patients switching from EVG/Cobi/FTC/TAF to BIC/FTC/TAF in clinical practice. Methods: A group of subjects switching from EVG/Cobi/FTC/TAF to BIC/F/TAF was prospectively followed. A validated sleep quality questionnaire (Pittsburgh Sleep Quality Index), as well as the Hospital Anxiety and Depression Scale (HADS), were administered after 4 weeks from the treatment switch. Adverse events, side effects and discontinuation were recorded at weeks 4 and 24. Pretreatment switch and week 24 body weight and laboratory data were compared. Results: A total of 96 virologically suppressed patients (86% male) were included. All patients received EVG/Cobi/FTC/TAF at least 1 year before the treatment switch. Median (IQR) nadir CD4 was 367 (263). The most common comorbidities were dyslipidemia, HTA and diabetes, 26%, 14% and 7%, respectively. Depression was reported by 8%. Five patients discontinued BIC/FTC/TAF before week 4 due to intolerance (2 insomnia, 1 headache and 2 GI symptoms). No changes in sleep quality, anxiety and depression outcomes were observed at week 4 (p = 0.1, p = 0.1 and p = 0.3, respectively). After 6 months, the median body weight change was statistically significant (0.6 kg, p = 0.003). All patients maintained HIV suppression. Conclusion: Except in a few cases, sleep quality, anxiety and depression symptoms remain stable in HIV virologically suppressed patients on EVG/Cobi/FTC/TAF who switch to BIC/F/TAF. NPAEs are mild and tend to occur in those with previous neuropsychiatric symptoms. Weight gain tends to be small but statistically significant. Long-term follow-up in “real-life” cohorts would be needed to confirm these findings.

Background: The necessity for newer anti-HIV and anti-tubercular medications has arisen as a result of the prevalence of opportunistic infections caused by HIV (human immunodeficiency virus). Objective: A series of ten new hydrazono 1,3-thiazolidin-4-one derivatives were synthesized in one-pot and evaluated for anti-HIV and anti-tubercular activities. Molecular Docking was accomplished with HIV-1 reverse transcriptase protein (PDB ID: 1REV) and Mycobacterium Tuberculosis (M. tuberculosis) H37Rv protein (PDB ID: 2YES) receptors along with drug-likeness and ADMET properties. Methods: One-pot synthesis of hydrazono 1,3-thiazolidin-4-one derivatives was carried out by ketones, thiosemicarbazide and ethylchloroacetate with the catalyst of anhydrous sodium acetate. All the synthesized compounds were characterized and evaluated for their in-vitro anti-HIV and also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv. In-silico predicted physicochemical parameters were done by MedChem DesignerTM software version 5.5 and ADMET parameters by pkCSM online tool. Furthermore, molecular docking was performed with pyrx 0.8 by autodock vina software. Results: All the synthesized compounds were characterized and evaluated for their in-vitro anti- HIV activity for inhibition of syncytia formation, which shows KTE1 with EC50 47.95 μM and Selectivity Index (SI) of >4.17 and for inhibition of p24 antigen production EC50 was found to be 80.02 μM and SI of >2.49. The compounds were also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv, in which KTE1 MIC values of 12.5μg/ml with SI of >4.0 and cytotoxicity against Vero cell lines. In-silico predicted physicochemical parameters for synthesized compounds which were found to be drug-like. Furthermore, docking has shown a good dock score and binding energy with anti-HIV and anti-tubercular receptors. Conclusion: From the novel synthesized molecules, none of the molecule is as effective as standards for anti-HIV and anti-tubercular drugs and hence can be further explored for its potential activities. Furthermore, derivatization was made to achieve more potent compounds for anti-HIV and anti-tubercular drugs.