Safety and Efficacy of Triple Therapy With Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors in Treatment-Naive Human Immunodeficiency Virus Type 2 Patients: Results From a 48-Week Phase 2 Study.

BACKGROUND: Integrase strand transfer inhibitor-based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. METHODS: We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. RESULTS: A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99-445). The median CD4 count was 438 cells/µL (IQR, 335-605), and the CD4/CD8 ratio was 0.8. Three patients discontinued the study. At week 48, all participants (27) had pVL <40 copies/mL. No virological failures were observed. Mean changes in CD4 count and CD4/CD8 ratio at week 48 were 95.59 cells/µL (95% confidence interval [CI], 28-163) and 0.32 (95% CI, .19 to .46). The most common drug-related adverse events were headache and nausea. One participant discontinued due to central nervous system symptoms. No serious adverse events were reported. CONCLUSIONS: DTG plus 2 NRTIs is safe and effective as first-line treatment for PWHIV-2 with a tolerability profile previously known. No virological failures were observed that suggest a high potency of DTG in HIV-2 as occurs in HIV-1. CLINICAL TRIALS REGISTRATION: M NCT03224338.

Antibody response against selected epitopes in the HIV-1 envelope gp41 ectodomain contributes to reduce viral burden in HIV-1 infected patients.

The ectodomain of gp41 is the target of potent binding and neutralizing antibodies (NAbs) and is being explored in new strategies for antibody-based HIV vaccines. Previous studies have suggested that the W164A-3S (3S) and EC26-2A4 (EC26) peptides located in the gp41 ectodomain may be potential HIV vaccine candidates. We assessed 3S- and EC26-specific binding antibody responses and related neutralizing activity in a large panel of chronic HIV-1-infected Portuguese individuals on ART. A similar proportion of participants had antibodies binding to 3S (9.6%) and EC26 (9.9%) peptides but the level of reactivity against 3S was significantly higher compared to EC26, except in the rare patients with double peptide reactivity. The higher antigenicity of 3S was unrelated with disease stage, as assessed by CD4+ T cell counts, but it was directly related with plasma viral load. Most patients that were tested (89.9%, N = 268) showed tier 1 neutralizing activity, the potency being inversely associated with plasma viral load. In the subset of patients that were tested for neutralization of tier 2 isolates, neutralization breadth was inversely correlated with plasma viral load and directly correlated with CD4+ T cell counts. These results are consistent with a role for neutralizing antibodies in controlling viral replication and preventing the decline of CD4+ T lymphocytes. Importantly, in patients with 3S-specific antibodies, neutralizing titers were inversely correlated with viral RNA levels and proviral DNA levels. Moreover, patients with 3S and/or EC26-specific antibodies showed a 1.9-fold higher tier 2 neutralization score than patients without antibodies suggesting that 3S and/or EC26-specific antibodies contribute to neutralization breadth and potency in HIV-1 infected patients. Overall, these results suggest that antibodies targeting the S3 and EC26 epitopes may contribute to reduce viral burden and provide further support for the inclusion of 3S and EC26 epitopes in HIV-1 vaccine candidates.

Bacillary angiomatosis in a HIV-positive patient with poor adherence to antiretroviral therapy.

Bacillary angiomatosis is a systemic disease caused by Bartonella (B.) henselae and B. quintana. Today it is a rare disease that occurs predominantly in patients with poor adherence to antiretroviral therapy or with late diagnosis of human immunodeficiency virus (HIV). We report on the case of a 40-year-old Caucasian female with HIV-1 and hepatitis B virus (HBV) co-infection diagnosed 17 years ago. She presented to the emergency department with an erythematous, painless nodule located on the left naso-genian fold. In the next few weeks the disease disseminated to the oral and left tarsal mucosa and to the palm of the left hand. The histopathological findings were suggestive of bacillary angiomatosis which was confirmed by polymerase chain reaction (PCR). The patient was treated with clarithromycin 500 mg bid per os for 3 months, with complete remission of the mucocutaneous lesions. Bacillary angiomatosis is a potentially fatal disease. Early diagnosis and treatment are critical in reducing the morbidity and mortality associated with it.

[Toscana virus in the Portuguese population: serosurvey and clinical cases]. / Vírus Toscana na população Portuguesa: vigilância sero-epidemiológica e casos clínicos.

Toscana virus (Phlebovirus genus, Bunyaviridae family) is a neurotropic virus which circulates in the Mediterranean Basin. Although Portugal has been the second country where its presence was reported, the existence of this virus in our country has been referred only sporadically, and there is a lack of knowledge regarding the prevalence of antibodies in the population. Thus, the objective of this study was to analyse the prevalence of antibodies anti-Toscana virus in the human population in our country. Sero-epidemiological investigations were performed with indirect immunofluorescence assay (IFA) and enzyme linked immunosorbent assay (ELISA) tests. The study population consisted of a control population (blood donors, n=150), a population considered at risk (n=236) and a population of individuals with symptoms and laboratory diagnostic request for vector-borne viruses. The latter population was divided into two groups: those individuals with neurological symptoms (n=165) and those without neurological symptoms (n=373). We tested sera from a total of 924 individuals. The seroprevalence of IgG antibodies in the control population was 2%. In the population considered at risk, the prevalence was 3.4%. In the population with central nervous system disease, we detected a seroprevalence of 4.2%. For the same type of antibodies and in subjects without central nervous system disease, the prevalence was 1.3%. Five cases of recent infection (3%) were detected in the population with neurological signs. Those infections have been acquired in the districts of Faro, Coimbra, Aveiro and Lisbon. The associated clinical diagnoses were meningitis, meningoencephalitis and rash. The observed seroprevalences were, in general, lower than reported in other endemic countries. Only 5 of the 29 sera which gave positive results by IFA and ELISA were confirmed by plaque reduction neutralization tests with the Italian strain ISS.Phl.3. This can indicate the presence of more than one Toscana virus serotype circulating in Portugal and emphasizes the need for more research about this etiological agent in our country.