Lamivudine (3TC)/dolutegravir (DTG) single tablet regimen (STR) has shown long-term efficacy and tolerability in people living with HIV (PLWH). Dolutegravir has been approved for use in children, while data on the efficacy of 3TC plus DTG in maintaining virological suppression in this population are still under evaluation. In this case series, we describe three children with perinatally acquired HIV who maintained virological suppression after switching antiretroviral therapy to DTG/3TC. We present three case reports of three children enrolled in the Italian Register for HIV Infection in Children: a 9-year-old boy, a 10-year-old girl, and a 2-year-old girl with perinatally acquired HIV who immediately started antiretroviral therapy with a three-drug regimen upon diagnosis, which occurred at delivery, after 6 months of life, and after 2 years of life, respectively. They achieved and maintain virological suppression after 1, 6, and 7 months of therapy, respectively; then a switch strategy was performed with a two-drug regimen with DTG/3TC STR at the age of 7 years for the first child and at the age of 9 years for the second, while the third was switched to a DTG plus 3TC not STR, owing to weight requirements, at the age of 2 years and 10 months. All children maintained virological suppression at last follow-up visit (January 2024), showing an excellent growth curve and maintaining good adherence and tolerability to DTG plus 3TC. A two-drug regimen with DTG/3TC demonstrated efficacy in maintaining virological suppression in a switch strategy in these children, with important advantages such as better tolerability and comfort of taking a single tablet once daily.

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV). HIV protease, reverse transcriptase, and integrase are targets of current drugs to treat the disease. However, anti-viral drug-resistant strains have emerged quickly due to the high mutation rate of the virus, leading to the demand for the development of new drugs. One attractive target is Gag-Pol polyprotein, which plays a key role in the life cycle of HIV. Recently, we found that a combination of M50I and V151I mutations in HIV-1 integrase can suppress virus release and inhibit the initiation of Gag-Pol autoprocessing and maturation without interfering with the dimerization of Gag-Pol. Additional mutations in integrase or RNase H domain in reverse transcriptase can compensate for the defect. However, the molecular mechanism is unknown. There is no tertiary structure of the full-length HIV-1 Pol protein available for further study. Therefore, we developed a workflow to predict the tertiary structure of HIV-1 NL4.3 Pol polyprotein. The modeled structure has comparable quality compared with the recently published partial HIV-1 Pol structure (PDB ID: 7SJX). Our HIV-1 NL4.3 Pol dimer model is the first full-length Pol tertiary structure. It can provide a structural platform for studying the autoprocessing mechanism of HIV-1 Pol and for developing new potent drugs. Moreover, the workflow can be used to predict other large protein structures that cannot be resolved via conventional experimental methods.

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This longitudinal, case-control study aimed to investigate the role of thrombopoietin (TPO) and anti-TPO antibodies in HIV-associated thrombocytopenia, focusing on the changes seen before and after the initiation of highly active antiretroviral therapy (HAART). Patients were assessed before and at least six months after the initiation of HAART. In total, 75 PLWHIV (age/sex-matched and randomized at 2:1, according to thrombocytopenia status) were included in this study. The baseline assessment revealed significantly higher TPO levels in thrombocytopenic patients (140.45 vs. 106.8 mg/mL, p = 0.008). Furthermore, anti-TPO-positive patients displayed lower platelet counts (109,000 vs. 139,000/L, p = 0.002) and TPO levels (114.7 vs. 142.7 mg/mL, p = 0.047). Longitudinally, HAART initiation reduced the frequency of thrombocytopenia from 75.47% to 33.96% (p < 0.001) and elevated the median platelet counts from 131,000 to 199,000 (p < 0.001). No significant difference in median platelet counts was found post-HAART among the anti-TPO subgroups (p = 0.338), a result contrasting with pre-HAART findings (p = 0.043). Changes in anti-TPO status corresponded with significant platelet count alterations (p = 0.036). Notably, patients who became anti-TPO negative showed a median increase of 95,000 platelets (IQR: 43,750-199,500). These marked differences between subgroups underscore the potential role of anti-TPO antibodies in modulating the hematological response to HAART. Further research is needed to elucidate the complex interplay between HIV infection, HAART, and thrombocytopenia.

BACKGROUND: Selection of an antiretroviral regimen for people living with HIV (PLWH) involves various clinical considerations, such as comorbidities, archived drug resistance mutations, concomitant medications, and potential drug interactions and side effects. Alterations in the surface area and pH of the gastrointestinal tract following bariatric surgery may alter absorption, antiretroviral pharmacokinetics and viral suppression. Data on the efficacy of antiretroviral (ARV) therapy in PLWH who have undergone bariatric surgery are limited or lacking for new antiretrovirals, such as dolutegravir and bictegravir.
METHODS: This case series reports virologic outcomes and side effects in eight cases of PLWH receiving ARV therapy who underwent bariatric surgery. A systematic literature review was performed to review the available literature on the efficacy and safety of antiretroviral regimens in PLWH who have undergone bariatric surgery.
RESULTS: Virologic suppression was not impacted for obese PLWH who underwent bariatric surgery following failure of life-style modifications and pharmacological therapy.
CONCLUSIONS: There were no deleterious effects on HIV progression for PLWH that underwent bariatric surgery. More prospective research is required to validate the effects of bariatric surgery on immunologic and virologic function outcomes. Close involvement of HIV and surgical specialists is recommended to manage ARV therapy in patients undergoing bariatric surgery.

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Antiretroviral therapy (ART) has led to a decline in human immunodeficiency virus (HIV)-related mortality, but comorbidities, including organ dysfunction, are increasingly the focus of care. Heart transplant (HT) is a very effective therapeutic strategy for end-stage heart failure (HF); however, clinicians may be hesitant due to concerns of complex drug-drug interactions (DDIs) between ART and HT immunosuppressive regimens and the potential impact of ART on long-term HT outcomes. In this report, we describe long-term (76-month) follow-up of a patient with HIV-positive status who underwent orthotopic HT with special emphasis on complex drug interactions.
A 58-year-old man with HIV-1 developed ischemic cardiomyopathy, progressed to end-stage HF and underwent orthotopic HT. To avoid DDIs with planned immunosuppressive therapies, the ART regimen was modified to consist of lamivudine, tenofovir disoproxil fumarate, rilpivirine, and raltegravir. Following HT, the patient\'s immunosuppression consisted of tacrolimus and mycophenolate mofetil. He has had normal cardiac function and no opportunistic infections and was subsequently switched to tenofovir alafenamide, emtricitabine, and bictegravir in combination for convenience. Serial HIV-1 RNA blood levels were constantly below the limit of quantification, and his CD4 count remained above 200 cells/mm3 (30-35%). Several DDIs were identified and addressed; however, his long-term post-HT complications included one episode of asymptomatic acute cellular rejection, adenocarcinoma of the prostate, basal cell carcinoma, cardiac allograft vasculopathy, and peripheral neuropathy.
The clinical outcome of this case supports the conclusion of previously published reports, summarized here within, demonstrating that HIV-1 positive status should not preclude HT in carefully selected individuals. Both addressing potential DDIs prior to HT and long-term monitoring for routine post-transplant complications and secondary and incidental malignancies are imperative.

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Human immunodeficiency virus (HIV) infection is associated with a myriad of musculoskeletal manifestations. Inflammatory arthritis has been described in association with HIV in both adults and children. Biologic disease-modifying anti-rheumatic drugs, particularly tumor necrosis factor inhibitors (TNFi), have been reported to manage inflammatory arthritis in adults with HIV when conventional therapy fails to control arthritis. In this report, we describe the management of arthritis and enthesitis in a 12-year-old adolescent male with HIV using the TNFi adalimumab. At the time of presentation, the patient was on highly active antiretroviral therapy for 1 year. His viral load was <40 copies/mL, and the CD4+ T-cell count was 1280 cells/mm3 . He had a positive antinuclear antibody and HLA-B27. Rheumatoid factor was negative. After screening for hepatitis B and C and latent tuberculosis, the patient was started on adalimumab. This report describes the successful control of recalcitrant arthritis and enthesitis in a pediatric patient with HIV infection using adalimumab.

Bullous pemphigoid (BP) is an autoimmune inflammatory skin disease, mostly affecting the elderly population. Therefore, patients often have multiple comorbidities, but there is inconsistent data regarding the relationship between HIV-1 infection and BP, which has been rarely reported in combination. Herein, we describe three patients who presented with BP and concomitant HIV-1 infection that was well controlled with modern combined antiretroviral therapy. All patients received topical and oral corticosteroids. Depending on the individual severity, further add-on therapeutics, such as azathioprine, dapsone, doxycycline and the interleukin 4/13 antibody dupilumab, were added to the therapy regimen. All patients recovered from pruritic skin lesions and blistering. The cases are further discussed in the context of the current study landscape. In conclusion, HIV-1 infection shifts the cytokine profile from T-helper type 1 (TH1) towards T-helper type 2 (TH2), resulting in the excessive secretion of distinct cytokines, such as interleukin 4 (IL-4) and interleukin 10 (IL-10). With IL-4 being a main driver in the pathogenesis of BP, HIV-1-positive patients may benefit greatly from targeting IL-4 with monoclonal antibodies.