Human Immunodeficiency Virus Antiretroviral Therapy Research Articles

Abstract PO2-20-11: Safety and efficacy of KEYNOTE-522 in combination with anti-retroviral therapy in a patient with HIV and triple-negative breast cancer

Abstract Introduction: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that does not express estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER-2), accounting for about 15% of all BC. TNBC is more aggressive than other BC with a higher risk of recurrence and mortality. The current standard of care for high-risk, early-stage TNBC based on the KEYNOTE-522 trial is neoadjuvant multidrug chemotherapy (paclitaxel and carboplatin [TCb] weekly x 12 weeks and doxorubicin and cyclophosphamide [AC] Q3 weeks) with pembrolizumab (P). The trial demonstrated patients who received chemotherapy plus P had a higher pathological complete response and event-free survival compared to patients who received chemotherapy plus placebo. However, the trial excluded patients with any autoimmune disease requiring treatment within 2 years, a diagnosis of immunodeficiency or steroids within 7 days before the first treatment, or a known history of human immunodeficiency virus (HIV). While limited data exist on immune checkpoint inhibitors (ICI) in patients with immunodeficiencies, subsequent data demonstrate that patients with HIV have similar efficacy and immune-related adverse events (irAE) compared to patients without HIV, and 2017 consensus recommendations encouraged broader eligibility in clinical trials to include patients with HIV. We present one of the first reported clinical cases of a patient with HIV diagnosed with stage IIB TNBC, treated per KEYNOTE-522 and anti-retroviral therapy (ART). Clinical Case: A 55-year-old female with a medical history significant for HIV, self-detected a mass in her left breast. Diagnostic imaging demonstrated a suspicious 4.0 cm mass in the left breast without adenopathy. An ultrasound-guided biopsy of the mass revealed grade 3 invasive ductal carcinoma with ER 0%, PR < 1%, and HER-2 1+. The clinical stage was cT2N0M0, prognostic stage IIB. Genetic testing was positive for germline BRCA2 pathogenic variant. HIV PCR < 20 copies/mL and CD4 count 1.298 K/uL prior to neoadjuvant chemotherapy. The patient was adherent to HIV ART with bictegravir, emtricitabine, and tenofovir alafenamide. The patient received KEYNOTE-522, including 11 cycles of TCb-P, followed by four cycles of AC-P. Following neoadjuvant treatment, the patient underwent a left segmental mastectomy and sentinel lymph node biopsy and achieved a pathological complete response. She completed left whole breast radiation (RT) with 3DCRT plus 3DCRT tumor bed boost to a total dose of 48.06 cGy and one-year of adjuvant P. Treatment-related adverse events included grade 4 febrile neutropenia after cycle one AC without growth factor, requiring a 5-day hospitalization; and grade 3 peripheral neuropathy, resulting in discontinuation of week 12 of TCb. The patient also developed paronychia, and a pulmonary embolism after week 11 of TCb. She had no irAE. Radiation-related adverse events included grade 1 left breast dermatitis and fatigue and mild left breast soreness. Discussion: Among the subset of patients diagnosed with TNBC, the percentage of patients with HIV or immunodeficiency receiving active BC treatment is low. Safety and efficacy data for novel cancer therapeutics including ICI are limited since historically patients with HIV and other immunodeficiency states were excluded from trials. Anti-PD-1 ICI has become a key part of the standard of care for the treatment of breast cancer. Patients with HIV experience rare infectious complications and have a life expectancy near the general population with ART. We support the inclusion of patients with HIV in future clinical trials for TNBC and/or ICI and recommend treatment of patients with HIV and TNBC per standard of care in multi-disciplinary collaboration with HIV clinicians. Citation Format: Stephanie Haddad, Stephanie Graff, Matthew Hadfield, Yihong Wang, Charu Taneja, Kara Leonard, Martha Sanchez, Robert Ward, Ana Lourenco, Mary Anne Fenton. Safety and efficacy of KEYNOTE-522 in combination with anti-retroviral therapy in a patient with HIV and triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-20-11.

Emotion regulation as a potential moderator of the association between HIV stigma and nonadherence to antiretroviral therapy among youth living with HIV.

Human immunodeficiency virus (HIV)-related stigma affects adherence to antiretroviral therapy (ART) for youth living with HIV. Emotion regulation strategies such as cognitive reappraisal (reinterpreting adversity to mitigate emotional impact) and expressive suppression (inhibiting emotion-expressive behavior activated by adversity) may moderate the HIV stigma-ART adherence relationship in this group. Using baseline data from 208 youth living with HIV aged 15-24 years enrolled in an mHealth ART-adherence intervention, we performed modified Poisson regressions with robust variance between HIV stigma (internalized, anticipated, enacted) and ART nonadherence. We tested for multiplicative interaction via product terms between HIV stigma and emotion regulation scores, and additive interaction via relative excess risk due to interaction and attributable proportion using dichotomous HIV stigma and emotion regulation variables. Mean age was 21 years; ≥50% of participants were cisgender male, non-Hispanic Black, and gay-identifying; 18% reported ART nonadherence. Confounder-adjusted regressions showed positive associations between each HIV stigma variable and ART nonadherence. Internalized HIV stigma and cognitive reappraisal negatively, multiplicatively interacted (as internalized HIV stigma increased, ART nonadherence increased for those with low cognitive reappraisal). High internalized HIV stigma positively, additively interacted with low cognitive reappraisal and low expressive suppression (when high internalized HIV stigma and low levels of either emotion regulation strategy were present, ART nonadherence increased dramatically). Cognitive reappraisal and expressive suppression may protect against internalized HIV stigma's harmful association with ART nonadherence. These modifiable emotion regulation strategies may be targeted to potentially buffer the effects of internalized HIV stigma and support ART adherence for youth living with HIV.

Safeguarding strategies and current HIV treatment in the UK

Objectives: This study aims to illuminate contemporary strategies and treatment approaches employed in the United Kingdom (UK) to safeguard against Human Immunodeficiency Virus (HIV) transmission and enhance the well-being of those grappling with Acquired Immune Deficiency Syndrome (AIDS). The review contributes to a comprehensive understanding of the nation's ongoing efforts in managing the impact of HIV on public health. Material and Methods: Research, reports, guidelines, and official websites from 2005 to 2024 were searched from the Pubmed database and Bournemouth University's database. English resources were searched using keywords related to HIV risk measures, pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), and anti-retroviral therapy (ART). Results: HIV prevention efforts in the UK emphasize education, widespread testing, and targeted interventions. Strategies include promoting safe sex practices, regular testing, and condom use. HIV testing, PrEP, PEP and ART play crucial roles in prevention and treatment, with initiatives focusing on high-risk populations such as men who have sex with men (MSM) and transgender individuals. Challenges include regional variations, financial constraints, and social stigma. Conclusions: A holistic and adaptable approach is essential in HIV prevention and treatment in the UK. Education, widespread testing, and tailored interventions for diverse populations are key components. Challenges such as financial constraints and social stigma require sustained efforts and global collaboration. Advancements in PrEP, PEP, and ART offer promising avenues for mitigating the impact of HIV, emphasizing the importance of accessibility and adherence.

Baseline Haematological Evaluation in Individuals Prior to Initiating Antiretroviral Therapy for HIV

Introduction: Human immunodeficiency virus (HIV) was discovered in 1983, while acquired immunodeficiency syndrome (AIDS) was first detected in 1981. Since then, it continues to be a public health problem. The phenomenon of HIV/AIDS is best viewed as a pandemic affecting almost all countries of the world. The first case of HIV/AIDS in Bangladesh was documented in 1989.This study was conducted to evaluate the baseline haematologicalcharacteristic in individuals prior to initiating antiretroviral therapy for HIV. Methods: This study was a cross sectional analytical study conducted among one hundred and fifty-four HIV positive patients attending at ART center, Bangabandhu Sheikh Mujib Medical University. Patients were included as per inclusion and exclusion criteria. Co-morbid conditions were excluded mostly by self-reporting and clinically relevant investigations. Result:The study revealed that HIV infected patients were predominantly middle-aged and young comprising > 70% of the patients with the mean age of the patients being 35.5 ± 9.5 years (range: 20-60 years). A male preponderance was observed in the study with a male-to-female ratio being 3:1. The majority (92.2%) of patients received first-line ART. The red cell indices like Hct, MCV, MCH, and MCHC were also low at the initiation of therapy but changed to normality after treatment. Conclusion: From the findings of the study, it can be concluded that HIV infected individuals are predominantly male, middle-aged, and young. The most common haematological abnormality is anaemia which is significantly reduced in percentage after a mean treatment period of nine and a half months with ART. Bangladesh J Medicine 2024; 35(1): 26-32

Incident Kaposi sarcoma during the expansion of antiretroviral therapy eligibility in Nigeria: a retrospective cohort study

IntroductionThe expansion of antiretroviral therapy (ART) eligibility could lead to earlier initiation of Human Immunodeficiency Virus (HIV) treatment and consequently reduce the risk of HIV-associated Kaposi Sarcoma (KS). We investigated the impact of changes in the Nigerian HIV treatment guidelines on KS incidence among adults enrolled in HIV care in Nigeria.MethodsWe analyzed data of adults who enrolled for HIV care from January 2006 to December 2016 at one of Nigeria’s largest HIV treatment centers. Based on changes in HIV treatment guidelines, we classified 2006–2009 as the pre-expansion period and 2010–2016 as the post-expansion period. We used Kaplan Meier curves to compare the incidence of KS in the pre-expansion to the post-expansion period. We used Cox regression models to assess the hazard for incident KS between the two periods after adjusting for potential confounders.ResultsAmong 14,479 patients with HIV, the overall KS incidence was 2.35; 95% CI 2.01–2.74/1,000 person-years. The incidence of KS decreased from 2.53 to 1.58 per 1,000 person-years from 2006 to 2009 to 2010–2016. In models adjusting for age, sex, CD4-T cell count, and ART use, the risk for KS remained lower in 2010–2016 compared to 2006–2009. In analyses restricted to time on ART, there was no significant difference in KS incidence between HIV patients who enrolled in 2006–2009 and 2010–2016 after adjusting for age, sex, and CD4 T-cell count.ConclusionThe expansion of ART eligibility was associated with a reduced incidence of HIV-associated KS among adults initiating HIV care in Jos, Nigeria. The reduction was likely driven by earlier enrollment for HIV care and ART initiation.

Modeling one-stop-shop integration of family planning and HIV services in Zimbabwe, 2021

Objectives: In October 2020, the Ministry of Health and Child-care Zimbabwe commenced integrating reproductive health with human immunodeficiency virus (HIV) services. Family planning (FP), sexually transmitted infection (STI) screening and treatment, HIV testing services (HTS), pre-exposure prophylaxis (PrEP), and antiretroviral therapy (ART) services were offered through an integrated one-stop-shop model. The project aimed to address unacceptably high incidences of HIV and STIs among FP clients and demonstrate improved access and uptake of integrated services at dedicated FP centers. Materials and Methods: We conducted an intervention study. A service package of STI symptom screening and HTS (including HIV self-test [HIVST] primary and secondary distribution) was offered to all FP clients by multi-skilled nurses. Service uptake was measured pre and post-introduction of the intervention, before which services were provided by different nurses, in different rooms. HIV-diagnosed clients were linked to ART and eligible negative testers were offered PrEP. Service uptake was measured at 1 year of implementation against the same period before. Results: A total of 20,947 clients were recruited between October 2019 and September 2021, 9386 pre-intervention and 11,561 post-intervention. We observed a 5.2% total increase in clients seen and a 27.1% increase in the average uptake of all integrated services (FP, STI, HTS, PrEP, and ART). Most (93.5%) clients received oral contraception (Progestogen-only pills and combined-oral-contraceptives), while fewer (4.8%) received injectables and implants (1.1%). Following the intervention, STI screening increased by 30.2% (2730 vs. 11,028). HTS delivery increased by 38.9% and PrEP by 44.1%. HIV positivity yield increased significantly (10.1%, 62/615 vs. 16.6%, 813/4910) and linkage to ART improved by 44.4%. HIVST distribution contributed to improved access to HIV testing with 3754 FP clients accepting distribution compared with 4910 receiving HTS by nurses, provider-delivered testing was accessed by reactive self-testers. The project increased (?) improved linkage to preventive and treatment services and reduced missed opportunities associated with fragmented services. Conclusion: The integrated one-stop-shop model demonstrated improved service uptake during the intervention period. This project shows the benefits of integrated FP/STI/HTS/PrEP in Zimbabwe’s high HIV burden settings.

Assessment of protein s and c level and its relationship with health-related factors in people living with hiv: a cross-sectional study

Introduction. Not only does Human Immunodeficiency Virus (HIV) threaten the complications associated with immunodeficiency, but also does it cause a set of chronic conditions that may lead to serious problems in these patients. Hypercoagulable state and other hematologic manifestations are reported as leading factors in various clinical problems like deep vein thrombosis in People Living with HIV (PLHIV). The present study aimed to investigate whether there is any correlation between proteins S and C levels (the thrombophilic conditions in HIV seropositive cases) and hematological factors, biochemical markers, CD4 count, HIV viral load, anti-retroviral therapy, Hepatitis C (HCV) and hepatitis B (HBV) confection, drug use, infectious diseases, and demographic characteristics.
 Materials and methods. Protein S and C levels in 100 PLHIV were measured. Coagulation tests, CD4 count, HIV viral load, biochemical and hematological factors, and infectious tests were measured in these cases to assess any possible correlation between these factors and the patients proteins S and C levels.
 Results. Protein S, and C deficiency among PLHIV 8% and 10%, respectively. Red blood cell, hemoglobin, hematocrit, fasting blood sugar, and albumin were directly related to protein S, and the patients with positive VDRL significantly had a lower level of protein S. The patients receiving anti-retroviral therapy and those with positive VDRL had a higher level of protein C. CD4 count, prothrombin time, and cholesterol had also a direct correlation with protein C level.
 Conclusion. According to our results and the reduction of protein S, protein C, and the other factors affecting the lifestyle of PLHIV, there is an urge to pay special attention to thromboembolic disease. Moreover, there is a more possibility of hemostatic imbalances and coagulation disorders in them.

Cytochrome P450 and Other Drug-Metabolizing Enzymes As Therapeutic Targets.

Cytochrome P450 and other families of drug-metabolizing enzymes are commonly thought of and studied for their ability to metabolize xenobiotics and other foreign entities as they are eliminated from the body. Equally as important, however, is the homeostatic role that many of these enzymes play in maintaining the proper levels of endogenous signaling molecules such as lipids, steroids, and eicosanoids as well as their ability to modulate protein-protein interactions involved in downstream signaling cascades. Throughout the years, many of these endogenous ligands or protein partners of drug-metabolizing enzymes have been associated with a wide range of disease states from cancer to various cardiovascular, neurologic, or inflammatory diseases, prompting an interest in whether modulation of drug-metabolizing enzyme activity could have a subsequent pharmacological impact or lessening of disease severity. Beyond direct regulation of endogenous pathways, drug-metabolizing enzymes have also been proactively targeted for their ability to activate prodrugs with subsequent pharmacological activity or enhance the efficacy of a coadministered drug by inhibiting the metabolism of that drug through a rationally designed drug-drug interaction (i.e., ritonavir and human immunodeficiency virus antiretroviral therapy). The focus of this minireview will be to highlight research aimed at characterizing cytochrome P450 and other drug-metabolizing enzymes as therapeutic targets. Examples of successfully marketed drugs as well as early research efforts will be discussed. Finally, emerging areas of research utilizing typical drug-metabolizing enzymes to impact clinical outcomes will be discussed. SIGNIFICANCE STATEMENT: Although generally thought of for their drug-metabolizing capabilities, enzymes such as the cytochromes P450, glutathione S-transferases, soluble epoxide hydrolases, and others play a significant role in regulating key endogenous pathways, making them potential drug targets. This minireview will cover various efforts over the years to modulate drug-metabolizing enzyme activity toward pharmacological outcomes.

HIV Replication Increases the Mitochondrial DNA Content of Plasma Extracellular Vesicles.

Extracellular vesicles (EVs) and their cargo have been studied intensively as potential sources of biomarkers in HIV infection; however, their DNA content, particularly the mitochondrial portion (mtDNA), remains largely unexplored. It is well known that human immunodeficiency virus (HIV) infection and prolonged antiretroviral therapy (ART) lead to mitochondrial dysfunction and reduced mtDNA copy in cells and tissues. Moreover, mtDNA is a well-known damage-associated molecular pattern molecule that could potentially contribute to increased immune activation, oxidative stress, and inflammatory response. We investigated the mtDNA content of large and small plasma EVs in persons living with HIV (PLWH) and its implications for viral replication, ART use, and immune status. Venous blood was collected from 196 PLWH, ART-treated or ART-naïve (66 with ongoing viral replication, ≥20 copies/mL), and from 53 HIV-negative persons, all recruited at five HIV testing or treatment centers in Burkina Faso. Large and small plasma EVs were purified and counted, and mtDNA level was measured by RT-qPCR. Regardless of HIV status, mtDNA was more abundant in large than small EVs. It was more abundant in EVs of viremic than aviremic and control participants and tended to be more abundant in participants treated with Tenofovir compared with Zidovudine. When ART treatment was longer than six months and viremia was undetectable, no variation in EV mtDNA content versus CD4 and CD8 count or CD4/CD8 ratio was observed. However, mtDNA in large and small EVs decreased with years of HIV infection and ART. Our results highlight the impact of viral replication and ART on large and small EVs' mtDNA content. The mechanisms underlying the differential incorporation of mtDNA into EVs and their effects on the surrounding cells warrant further investigation.

A prospective study to estimate the incidence and pattern of adverse drug reactions to first-line antiretroviral therapy (tenofovir, efavirenz, and lamivudine).

Antiretroviral drugs are efficacious but are associated with long-term toxicities, drug interactions, and emergence of drug resistance. To study the incidence and pattern of adverse drug reactions in human immunodeficiency virus (HIV) patients receiving first-line antiretroviral therapy (ART) (tenofovir, efavirenz, and lamivudine (TEL) which was introduced by NACO in 2013. A prospective, single-center observational study that included 135 treatment-naive HIV patients who were started on fixed drug once-daily regimen (TEL). At baseline, detailed clinical history, body weight, waist-hip ratio, complete blood count, liver and renal function test, CD4 cell count were performed. Clinical monitoring for cutaneous, neuropsychiatric, and gastrointestinal side effects was done every month along with laboratory monitoring and anthropometric measurement for every 6 months. CD4 counts were measured at baseline and end of the study at 12 months. Out of 135 participants, 89 (65.9%) were males and 46 (34%) were females. The mean age and the mean duration of illness at inclusion were 35.10 ± 8.97 years and 1.2 ± 0.6 years, respectively. The mean increase in weight at baseline and at 12 months (57.55 ± 6.56 to 64.04 ± 8.2) was statistically significant (95% confidence interval [CI]: 4.35-8.62, P < 0.001). The mean CD4 counts at baseline were 309.73 ± 118.44 and increased after 12 months of treatment to 421 ± 129.4 which was statistically significant (95% CI: 81.54-140.99, P < 0.001). The mean difference in platelet count was statistically significant between baseline and 12 months (95% CI: 10.32-46.13, P = 0.002). The mean difference in serum urea levels at baseline and at 6 months (95% CI: 0.60-1.61, P < 0.001) as well as 12 months were statistically significant (95% CI: 0.08-1.03, P = 0.02). The mean increase in serum creatinine at baseline (0.75 ± 0.12) and at 12 months (0.97 ± 0.16) was also significant (95% CI: 0.21-0.28, P < 0.001). There was a significant difference between mean creatinine clearance at baseline and at 12 months (109.9 ± 13.75 to 99.33 ± 12.52, P < 0.0001). One patient discontinued treatment due to adverse effects while two patients were shifted to second-line antiretroviral treatment. Small sample size, single-center study and short follow-up period, long-term toxicities were not appreciated. Fixed drug combination with TEL as a first-line ART for HIV is a safe regime as we observed minimal side effects with current regimen.

Scenario of HIV infection in Pakistan

Human immunodeficiency virus (HIV) infection, which was previously lethal, has evolved into a chronic disease that may be treated and well-managed. HIV levels in the bloodstream may become undetectable with antiretroviral therapy (ART). All those providing care for people living with HIV should be aware of the risk factors, transmission, diagnosis, and treatment, acute HIV infection, possible opportunistic infections, and malignancies. Preexposure and postexposure prophylaxis regimens allow for preventive treatment. Home healthcare specialists can help people follow their drug schedules, assess the effectiveness of their treatments, and identify HIV problems and ART side effects. The ability to support, inform, and counsel people living with HIV and their families is most crucial [1].&#x0D; Approximately 38.9 million people worldwide were living with HIV, 25.4 million had access to antiretroviral therapy (ART), 1.7 million had just recently contracted the virus, and 690,000 had passed away from AIDS-related illnesses, according to a Joint United Nations Program on HIV/AIDS 2020 report. Although Pakistan's national HIV/AIDS control program was established in 1987, the number of new HIV/AIDS cases has been rising quickly ever since. In Pakistan, 160,000 people were living with HIV/AIDS as of 2018, yet only 10% of them were receiving ART. 3 Increasing people with HIV/AIDS' access to ART has a number of positive effects, including delaying the advancement of the disease, extending life expectancy, and enhancing people's quality of life and mental health [2].&#x0D; "More than 1,000 new HIV cases are reported each month from all four provinces, including the capitol city Islamabad, Azad Kashmir, and Gilgit Baltistan. This demonstrates unequivocally that homosexuals, persons who inject drugs, male, female, and transgender sex workers, and other critical demographics are now spreading HIV to the broader community. During the final 10 months of 2022, 9,773 people in Pakistan had HIV tests that were positive, casting significant doubt on HIV preventive and control initiatives and amply demonstrating the spread of HIV from important populations to the general public. New HIV infections account for a sizable portion of low-risk males, females, and clients of critical communities, showing an increase in HIV transmission to bridging populations [3].&#x0D; The increased rate of HIV in Pakistan pose a risk to a healthy population, blood recipients etc. Therefore, surrounding communities should also be checked for HIV. The government should direct public education campaigns in coordination with NGOs. To prevent any future epidemics, barbers and unlicensed health professionals in remote regions should receive training.

Identification of novel lncRNAs associated with sensitivity of HIV antiretroviral therapy: A two-stage matched case-control study

BackgroundTo identify long non-coding RNAs (lncRNAs) that may be used as potential biomarkers of sensitivity to antiretroviral therapy (ART) against human immunodeficiency virus (HIV) infection. MethodA two-stage matched case-control study was conducted. First, in the screening stage, peripheral blood lymphocytes (PBLs) of six subjects receiving lamivudine-based ART (3 ART-resistant and 3 ART-sensitive subjects with matching durations of ART) were subjected to comprehensive microarray expression profiling in order to screen out lncRNAs associated with ART sensitivity. Secondly, during the validation stage, promising lncRNAs were evaluated via a 1:4 matched case-control study using 50 subjects (10 ART-resistant and 40 ART-sensitive subjects with matching durations of ART). ResultsSeven lncRNAs were screened out (P < 1.06 × 10-3) in the first stage. Among these, two lncRNAs (n341598 and n407911) survived validation conducted at the second stage (n341598: P < 0.001; n407911: P = 0.007), while another lncRNA n406445 showed marginally significant (P = 0.049). All three showed higher expression in ART-resistant subjects compared to that in ART-sensitive subjects. The area under the ROC curve (AUC) for n341598 was 0.867 (95 % CI: 0.796–0.966; P < 0.001), which was better than that for n406445 (0.702) and n407911 (0.780). Meanwhile, the AUC for n341598 was better than that of any combination of the three lncRNAs. ConclusionOur study identified three highly expressed lncRNAs in patients with HIV ART-resistant, among which the lncRNA n341598 may be utilized as an optimal biomarker to distinguish ART-resistant and ART-sensitive patients. Further studies aimed at revealing the molecular mechanisms underlying the regulation of ART sensitivity by n341598 are warranted to complement our findings.

The impact of dolutegravir-based combination antiretroviral therapy on the spermatozoa and fertility parameters of men living with human immunodeficiency virus.

The factors responsible for this reported fertility decline among human immunodeficiency virus (HIV) positive men is yet to be determined. This study is aimed at investigating the impact of HIV or combination antiretroviral therapy (cART) on sperm cells, reproductive hormones, oxidative stress markers, apoptosis, and sperm DNA fragmentation of men living with HIV. Twenty-one men living with HIV gave their written informed consent to participate in this study. Only 11 of the participants successfully donated blood and semen before and after 3 months of their treatment with cART. Semen, reproductive hormones, oxidative stress biomarkers, and DNA fragmentation were analysed. Data were subjected to Wilcoxon matched pairs signed rank test (ethical approval: CMUL/HREC/09/19/614). There was a significant decrease in viral load of HIV (p < 0.01), and a marked increase in progressive and total sperm motility. Total sperm count, morphology, and vitality had no significant change after 3 months of treatment with cART however, there was a significant increase (p < 0.05) in testosterone from 2.48 to 3.68 ng/ml, but luteinizing hormone decreased significantly (p < 0.05) from 9.6 to 6.5mIU/ml. In addition, sperm DNA fragmentation increased significantly (p < 0.01). Conversely, viral load, and catalase decreased significantly, but no significant difference in malondialdehyde. This study showed that HIV depleted testosterone and impaired sperm motility which may negatively affect the fertility potential of men living with HIV. It also showed that adherence to cART (a combination of tenofovir, lamivudine, and dolutegravir) reduces the viral load and reverses the deleterious effects of cART albeit, cART appears to be toxic at subcellular spermatogenic levels.

Impact of HAART Therapy and HIV Infection over Fetal Growth-An Anthropometric Point of View.

Human immunodeficiency virus (HIV) infection cannot be completely eliminated from the body because the virus integrates its genetic code into that of the host cell. The prevalence of pregnancy in women with HIV infection has increased due to the efficacy of antiretroviral therapy (ART). Placental insufficiency is associated with a reduction in blood flow and circulatory redistribution, resulting in fetal hypoxia and nutrient deprivation as a consequence of an altered placental function, and it can result in a lower birthweight. The aim of the study was to determine the combined effect of HIV infection and ART on the anthropometric parameters of infants born to HIV-positive pregnant women under ART compared to the values of these parameters in a control group of infants born to healthy mothers. There are no significant differences between the two groups in terms of gestational age at birth. We found a statistically significant lower birth weight in infants born from HIV-positive mothers under ART, with 3041 g in the control group compared to 2758 g in the group of HIV positive pregnant women (p < 0.01). There were statistically significant differences in all anthropometric parameters, these showing higher values in the control group (seronegative pregnant women).

Recent Synergy of Nanodiamonds: Role in Brain-Targeted Drug Delivery for the Management of Neurological Disorders.

The aim of the present review article is to summarize the role of nanodiamonds in various neurological diseases. We have taken related literature of making this review article from ScienceDirect, springer, Research gate, PubMed, Sci-finder, etc. The current approaches for treating neurological conditions such as glioblastoma includes chemotherapy or combination anti-retro viral therapy for HIV (human immunodeficiency virus) or use of anti-Alzheimer drugs during cognitive impairment. These approaches can provide only symptomatic relief as they do not target the cause of the disease due to their inability to penetrate the blood brain barrier. On long-term use, they may cause CNS toxicity due to accumulation in the brain. So nanodiamonds could prove as a promising approach in the brain targeting of the bioactive and to treat many neurological disorders such as Alzheimer's disease, Parkinson's disease, brain tumor (glioblastoma), HIV, amyotrophic multiple sclerosis, Huntington disease, stroke (cerebrovascular attack), batten disease, schizophrenia, epilepsy, and bacterial infections (encephalitis, sepsis, and meningitis) due to their ability to penetrate the blood-brain barrier and owing to their excellent surface properties, i.e., nano size and high surface area, ease of functionalization, multiple drug binding, and biocompatibility; they can be useful for brain targeted drug delivery with minimal side effects.

Macular Changes Observed on Optical Coherence Tomography Angiography in Patients Infected With Human Immunodeficiency Virus Without Infectious Retinopathy.

PurposeAs the human immunodeficiency virus (HIV) pandemic is far from over, whether there are subclinical macular changes in HIV-positive patients is something that should not be overlooked. We aimed to apply optical coherence tomography angiography (OCTA) to assess the macular structure and microvasculature changes in patients with HIV without infectious retinopathy.MethodsHIV-positive and -negative participants were included and classified into three groups: HIV-negative, HIV-positive, and HIV-positive with microvasculopathy. OCTA parameters regarding macular structure and microvasculature were analyzed.ResultsCompared with the HIV-negative group, the superficial retinal vessel density (VD) in the parafovea sectors and the whole Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and the choroidal vascularity index (CVI) in the whole ETDRS grid were significantly decreased in the HIV-positive and HIV-positive with microvasculopathy groups (p < 0.05). No differences were found in OCTA parameters between the HIV-positive and HIV-positive with microvasculopathy groups. Retinal, retinal nerve fiber layer-ganglion cell layer-inner plexiform layer (RNFL-GCL-IPL), RNFL, GCL-IPL, and INL thickness showed a negative association with the duration of HIV diagnosis or antiretroviral therapy (ART) (all p < 0.05). All OCTA microvasculature parameters showed no association with HIV-related clinical variables (all p > 0.05).ConclusionsSubclinical macular changes existed in HIV-infected patients without clinical infectious retinopathy. Substructures from inner retinal layers might be associated with HIV infection or ART duration.

Development of an Analytical Method for Determination of Related Substances and Degradation Products of Cabotegravir Using Analytical Quality by Design Principles.

Cabotegravir is one of the newly approved human immunodeficiency virus (HIV) integrase enzyme inhibitors used for the prevention and treatment of HIV infection. It is the first approved long-acting injectable antiretroviral therapy for HIV and is also very effective in combination with rilpivirine, a non-nucleoside reverse transcriptase inhibitor. Therefore, future drug development involving cabotegravir can be expected. We developed an ultrahigh performance liquid chromatography (UHPLC) method compatible with mass spectrometry for the determination of eight cabotegravir impurities. The described method is able to differentiate cabotegravir and its related substances as well as its degradation products. Analytical quality by design principles were used for method development. The method is robust within the defined method operable design region: flow rate = 0.32–0.40 mL/min; column temperature = 30–40 °C; pH of mobile phase A = 3.25–3.75, and the final percent of acetonitrile in gradient = 50.0–60.0%. Inside the method operable design region, a working optimal point was selected: pump flow rate = 0.36 mL/min; column temperature = 35 °C; pH of mobile phase A = 3.5, and final percent of acetonitrile in gradient = 55%. Method validation was performed, and the following parameters were verified: accuracy, repeatability, linearity, response factors, detection limit, and quantification limit. All method validation results were within selected criteria. The presented method could be used for the development of new pharmaceutical products based on cabotegravir.

Effects of viremia and CD4 recovery on gut "microbiome-immunity" axis in treatment-naïve HIV-1-infected patients undergoing antiretroviral therapy.

BACKGROUNDHuman immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Converging data from many cross-sectional studies suggest that gut microbiota (GM) changes can occur throughout including human immunodeficiency virus (HIV) infection, treated by ART; however, the results are contrasting. For the first time, we compared the fecal microbial composition, serum and fecal microbial metabolites, and serum cytokine profile of treatment-naïve patients before starting ART and after reaching virological suppression, after 24 wk of ART therapy. In addition, we compared the microbiota composition, microbial metabolites, and cytokine profile of patients with CD4/CD8 ratio < 1 (immunological non-responders [INRs]) and CD4/CD8 > 1 (immunological responders [IRs]), after 24 wk of ART therapy.AIMTo compare for the first time the fecal microbial composition, serum and fecal microbial metabolites, and serum cytokine profile of treatment-naïve patients before starting ART and after reaching virological suppression (HIV RNA < 50 copies/mL) after 24 wk of ART.METHODSWe enrolled 12 treatment-naïve HIV-infected patients receiving ART (mainly based on integrase inhibitors). Fecal microbiota composition was assessed through next generation sequencing. In addition, a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach. At the same time, serum free fatty acid (FFA) and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry.RESULTSWe first compared microbiota signatures, FFA levels, and cytokine profile before starting ART and after reaching virological suppression. Modest alterations were observed in microbiota composition, in particular in the viral suppression condition, we detected an increase of Ruminococcus and Succinivibrio and a decrease of Intestinibacter. Moreover, in the same condition, we also observed augmented levels of serum propionic and butyric acids. Contemporarily, a reduction of serum IP-10 and an increase of IL-8 levels were detected in the viral suppression condition. In addition, the same components were compared between IRs and INRs. Concerning the microflora population, we detected a reduction of Faecalibacterium and an increase of Alistipes in INRs. Simultaneously, fecal isobutyric, isovaleric, and 2-methylbutyric acids were also increased in INRs. CONCLUSIONOur results provided an additional perspective about the impact of HIV infection, ART, and immune recovery on the “microbiome-immunity axis” at the metabolism level. These factors can act as indicators of the active processes occurring in the gastrointestinal tract. Individuals with HIV-1 infection, before ART and after reaching virological suppression with 24 wk of ART, displayed a microbiota with unchanged overall bacterial diversity; moreover, their systemic inflammatory status seems not to be completely restored. In addition, we confirmed the role of the GM metabolites in immune reconstitution.

Outcomes of interventions to optimize linkage to HIV care and antiretroviral therapy (ART) initiation after HIV self-testing: A scoping review.

Human immunodeficiency virus (HIV) self-testing is an innovative solution to the problem of low HIV testing coverage. It can help in realizing the first "95" of the Joint United Nations Programme on HIV/AIDS targets in the HIV treatment cascade. However, there is limited information to guide how those who self-test and show positive results can successfully be linked to HIV care and treatment. Therefore, this scoping review aimed at synthesizing available evidence of the outcomes of intervention strategies to optimize linkage to HIV care after HIV self-testing. Our methodology followed Arksey and O'Malley's methodological framework. Two independent reviewers screened and extracted data based on predetermined criteria. The databases searched included PubMed, EBSCOhost, Web of Science, Cochrane Library, Scopus, Mednar, and the International Clinical Trials Registry Platform. A total of 4809 records were retrieved. After full-text screening, 14 studies met the inclusion criteria for the review. The intervention strategies reported were classified into four main categories: technology-assisted interventions, innovative HIV self-testing kits distribution mechanisms, financial incentive, social entrepreneurship models, and the use of key community opinion leaders and social media influencers. This scoping review found men who have sex with men as the main recipients of the interventions to improve the rate of linkage to HIV care following HIV self-testing. Studies that met the inclusion criteria reported mixed findings on the outcomes of interventions to improve the rate of linkage to HIV care following HIV self-testing. Financial incentives, interventions leveraging technology, and key opinion leaders were the most effective strategies. Given that the included studies did not employ a uniform system of measurement of effectiveness, there is a need for identification of standardized definitions and clear indicators for evaluating linkage to care and antiretroviral therapy (ART) initiation following HIV self-testing.

Treatment-adjusted prevalence to assess HIV testing programmes.

Scale-up of human immunodeficiency virus (HIV) testing and antiretroviral therapy (ART) for people living with HIV has been increasing in sub-Saharan Africa. As a result, areas with high HIV prevalence are finding a declining proportion of people testing positive in their national testing programmes. In eastern and southern Africa, where there are settings with adult HIV prevalence of 12% and above, the positivity from national HIV testing services has dropped to below 5%. Identifying those in need of ART is therefore becoming more costly for national HIV programmes. Annual target-setting assumes that national testing positivity rates approximate that of population prevalence. This assumption has generated an increased focus on testing approaches which achieve higher rates of HIV positivity. This trend is a departure from the provider-initiated testing and counselling strategy used early in the global HIV response. We discuss a new indicator, treatment-adjusted prevalence, that countries can use as a practical benchmark for estimating the expected adult positivity in a testing programme when accounting for both national HIV prevalence and ART coverage. The indicator is calculated by removing those people receiving ART from the numerator and denominator of HIV prevalence. Treatment-adjusted prevalence can be readily estimated from existing programme data and population estimates, and in 2019, was added to the World Health Organization guidelines for HIV testing and strategic information. Using country examples from Kenya, Malawi, South Sudan and Zimbabwe we illustrate how to apply this indicator and we discuss the potential public health implications of its use from the national to facility level.