Genotypic and Phenotypic Characterization of Replication-Competent HIV-2 Isolated from Controllers and Progressors.

Although some individuals with HIV-2 develop severe immunodeficiency and AIDS-related complications, most may never progress to AIDS. Replication-competent HIV-2 isolated from asymptomatic long-term non-progressors (controllers) have lower replication rates than viruses from individuals who progress to AIDS (progressors). To investigate potential retroviral factors that correlate with disease progression in HIV-2, we sequenced the near full-length genomes of replication-competent viruses previously outgrown from controllers and progressors and used phylogeny to seek genotypic correlates of disease progression.

Immune reconstitution inflammatory syndrome in HIV infected late presenters starting integrase inhibitor containing antiretroviral therapy.

Background: Integrase inhibitors (INI) induce a rapid decline of HIV-RNA in plasma and CD4 T-cell recovery in blood. Both characteristics are also associated with immune reconstitution inflammatory syndrome (IRIS). Whether the use of INI-containing combination antiretroviral therapy (cART) increases the risk of IRIS is being questioned.

Is HIV-1 viraemia below 20 copies/mL in antiretroviral-treated patients associated with virologic outcome?

Background: We aimed to investigate whether very low-level HIV-1 viraemia (VLLV) <20 copies/mL in HIV-1-infected patients on antiretroviral therapy (ART) whose VL was <20 copies/mL, was associated with a subsequent VL > 20 copies/mL.

Methods: VLLV was defined as VL <20 copies/mL and positive HIV-1-PCR. We compared patients with positive and negative HIV-1-PCRs <20 copies/mL at two time points, T0 and T1, after 21st of January 2016.

The S230R Integrase Substitution Associated With Virus Load Rebound During Dolutegravir Monotherapy Confers Low-Level Resistance to Integrase Strand-Transfer Inhibitors.

Background: Dolutegravir (DTG) is an integrase strand-transfer inhibitor (INSTI) used for treatment of human immunodeficiency virus (HIV)-infected individuals. Owing to its high genetic barrier to resistance, DTG has been clinically investigated as maintenance monotherapy to maintain viral suppression and to reduce complication and healthcare costs. Our study aims to explain the underlying mechanism related to the emergence of a S230R substitution in patients who experienced virologic failure while using DTG monotherapy.

HIV-1 Resistance Dynamics in Patients With Virologic Failure to Dolutegravir Maintenance Monotherapy.

Background: A high genetic barrier to resistance to the integrase strand transfer inhibitor (INSTI) dolutegravir has been reported in vitro and in vivo. We describe the dynamics of INSTI resistance-associated mutations (INSTI-RAMs) and mutations in the 3'-polypurine tract (3'-PPT) in relation to virologic failure (VF) observed in the randomized Dolutegravir as Maintenance Monotherapy for HIV-1 study (DOMONO, NCT02401828).

Methods: From 10 patients with VF, plasma samples were collected before the start of cART and during VF, and were used to generate Sanger sequences of integrase, the 5' terminal bases of the 3' long terminal repeat (LTR), and the 3'-PPT.

Preconception use of cART by HIV-positive pregnant women increases the risk of infants being born small for gestational age.

Background: The benefits of combination anti-retroviral therapy (cART) in HIV-positive pregnant women (improved maternal health and prevention of mother to child transmission [pMTCT]) currently outweigh the adverse effects due to cART. As the variety of cART increases, however, the question arises as to which type of cART is safest for pregnant women and women of childbearing age. We studied the effect of timing and exposure to different classes of cART on adverse birth outcomes in a large HIV cohort in the Netherlands.

A mutation in the progesterone receptor predisposes to HEV infection in HIV-positive patients.

Background And Aims: Infection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear.

Dolutegravir as maintenance monotherapy for HIV (DOMONO): a phase 2, randomised non-inferiority trial.

Background: The high genetic barrier to resistance of dolutegravir might allow for its use as maintenance monotherapy in patients with HIV. We investigated whether dolutegravir monotherapy was non-inferior to combination antiretroviral therapy (ART) for maintaining virological suppression in patients with HIV-1 infection successfully treated with combination ART.

Methods: We did this open-label, phase 2, randomised non-inferiority trial at two medical centres in the Netherlands.

Lowered Rilpivirine Exposure During the Third Trimester of Pregnancy in Human Immunodeficiency Virus Type 1-Infected Women.

Background: The use of antiretroviral therapy during pregnancy is important for control of maternal human immunodeficiency virus (HIV) disease and the prevention of perinatal HIV transmission. Physiological changes during pregnancy can reduce antiretroviral exposure. We studied the pharmacokinetics of rilpivirine 25 mg once daily in HIV-1-infected women during late pregnancy.

The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women.

Objective: To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum.

Factors associated with presenting late or with advanced HIV disease in the Netherlands, 1996-2014: results from a national observational cohort.

Objectives: Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands.

Methods: HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort.

Raltegravir in HIV-1-Infected Pregnant Women: Pharmacokinetics, Safety, and Efficacy.

Background: The use of raltegravir in human immunodeficiency virus (HIV)-infected pregnant women is important in the prevention of mother-to-child HIV transmission, especially in circumstances when a rapid decline of HIV RNA load is warranted or when preferred antiretroviral agents cannot be used. Physiological changes during pregnancy can reduce antiretroviral drug exposure. We studied the effect of pregnancy on the pharmacokinetics of raltegravir and its safety and efficacy in HIV-infected pregnant women.

von Willebrand Factor is elevated in HIV patients with a history of thrombosis.

Background: Arterial and venous thrombotic events are more prevalent in HIV infected individuals compared to the general population, even in the era of combination antiretroviral therapy. Although the mechanism is not fully understood, recent evidence suggests a role for chronic immune activation.

Methods: We reviewed the Dutch National HIV registry database for HIV infected patients in Rotterdam with a history of arterial or venous thrombosis and calculated the incidence.

Imiquimod 5% cream for five consecutive days a week in an HIV-infected observational cohort up to 32 weeks in the treatment of high-grade squamous intraepithelial lesions.

Objectives: The incidence of anal cancer is increasing especially in HIV-positive men having sex with men. Screening for the cancer precursor, high-grade squamous intraepithelial lesions (HSIL), is challenging, as current treatment is suboptimal. The aim of this prospective study was to establish the efficacy of five consecutive days a week self-administered treatment with imiquimod 5% cream for both perianal and intra-anal HSIL and to assess the adverse effects and burden of this regimen.

Pharmacokinetics of total and unbound darunavir in HIV-1-infected pregnant women.

Objectives: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum.

Patients And Methods: This was a non-randomized, open-label, multicentre, Phase IV study in HIV-infected pregnant women recruited from HIV treatment centres in Europe. HIV-infected pregnant women treated with darunavir (800/100 mg once daily or 600/100 mg twice daily) as part of their combination ART were included.

Atazanavir exposure is effective during pregnancy regardless of tenofovir use.

Background: We studied the effect of pregnancy on atazanavir pharmacokinetics in the presence and absence of tenofovir.

Methods: This was a non-randomized, open-label, multicentre Phase IV study in HIV-infected pregnant women recruited from European HIV treatment centres. HIV-infected pregnant women treated with boosted atazanavir (300/100 mg or 400/100 mg atazanavir/ritonavir) as part of their combination antiretroviral therapy (cART) were included in the study.

Peginterferon alfa-2a for AIDS-associated Kaposi sarcoma: experience with 10 patients.

In this observational cohort study, 10 patients with extensive or treatment-refractory AIDS-associated Kaposi sarcoma were treated with peginterferon alfa-2a. Tumor responses were observed in 9 patients with a median progression-free survival of 645 days. Peginterferon alfa-2a could be an effective therapy for extensive or treatment-resistant Kaposi sarcoma.

[Late diagnosis of HIV positive patients in Rotterdam, the Netherlands: risk factors and missed opportunities].

Objective: To determine the percentage of patients in whom the diagnosis 'HIV infection' was made late, which factors are associated with an increased risk of a late HIV diagnosis, and if there are opportunities for an earlier diagnosis.

Design: Retrospective analysis.

Method: We included all HIV positive patients who were treated at the Erasmus Medical Center Rotterdam in the period January 1996-March 2012.

The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals.

Background: The presence of a vpx gene distinguishes HIV-2 from HIV-1, the main causative agent of AIDS. Vpx degrades the restriction factor SAMHD1 to boost HIV-2 infection of macrophages and dendritic cells and it has been suggested that the activation of antiviral innate immune responses after Vpx-dependent infection of myeloid cells may explain why most HIV-2-infected individuals efficiently control viral replication and become long-term survivors. However, the role of Vpx-mediated SAMHD1 antagonism in the virological and clinical outcome of HIV-2 infection remained to be investigated.

Prolonged decrease of CD4+ T lymphocytes in HIV-1-infected patients after radiotherapy for a solid tumor.

Background: In HIV-negative patients, radiotherapy (RT) decreases CD4 T-cell counts. We studied the effects of RT in HIV-1 positive patients.

Methods: HIV-1 positive patients with a subsequent diagnosis of a solid tumor were selected from the Dutch national observational HIV cohort, Aids Therapy Evaluation in the Netherlands (ATHENA).

Long-term response rates of successful hepatitis B vaccination in HIV-infected patients.

Background: Data on long-term response rates after successful primary hepatitis B (HBV) vaccination in HIV-infected patients are scarce.

Objective: To evaluate the durability of an effective anti-HBs titer up to 5 years after primary vaccination in a cohort of 155 HIV-infected adults.

Methods: From a previous multicenter HBV vaccination trial we selected patients with an anti-HBs titer of ≥10 IU/l 28 weeks after the first vaccination.