The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)–B27 patients. To understand further the nature of CD8+ T cell–mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27–restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10–specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.

Objective. We report data on 11 patients with neurological symptoms and human immunodeficiency virus (HIV) cerebrospinal fluid (CSF) viremia contrast

Raltegravir (MK-0518) is a potent inhibitor of human immunodeficiency virus (HIV) integrase and is clinically effective against viruses resistant to other classes of antiretroviral agents. However, it can select mutations in the HIV integrase gene. Nine heavily pretreated patients who received salvage therapy including raltegravir and who subsequently developed virological failure under raltegravir therapy were studied. For each patient, the sequences of the integrase-coding region were determined and compared to that at the beginning of the treatment. Four different mutation profiles were identified in these nine patients: E92Q, G140S Q148H, N155H, and E157Q mutations. For four patients, each harboring a different profile, the wild-type and mutated integrases were produced, purified, and assayed in vitro. All the mutations identified altered the activities of integrase protein: both 3′ processing and strand transfer activities were moderately affected in the E92Q mutant; strand transfer was markedly impaired in the N155H mutant; both activities were strongly impaired in the G140S Q148H mutant; and the E157Q mutant was almost completely inactive. The sensitivities of wild-type and mutant integrases to raltegravir were compared. The E92Q and G140S Q148H profiles were each associated with a 7- to 8-fold decrease in sensitivity, and the N155H mutant was more than 14-fold less sensitive to raltegravir. At least four genetic profiles (E92Q, G140S Q148H, N155H, and E157Q) can be associated with in vivo treatment failure and resistance to raltegravir. These mutations led to strong impairment of enzymes in vitro in the absence of raltegravir: strand transfer activity was affected, and in some cases 3′ processing was also impaired.

There are only few data concerning persistence of neutralizing antibodies (NAbs) among SARS-CoV-2-infected healthcare workers (HCW). These individuals are particularly exposed to SARS-CoV-2 infection and at potential risk of reinfection. We followed 26 HCW with mild COVID-19 three weeks (D21), two months (M2) and three months (M3) after the onset of symptoms. All the HCW had anti-receptor binding domain (RBD) IgA at D21, decreasing to 38.5% at M3 (p < 0.0001). Concomitantly a significant decrease in NAb titers was observed between D21 and M2 (p = 0.03) and between D21 and M3 (p < 0.0001). Here, we report that SARS-CoV-2 can elicit a NAb response correlated with anti-RBD antibody levels. However, this neutralizing activity declines, and may even be lost, in association with a decrease in systemic IgA antibody levels, from two months after disease onset. This short-lasting humoral protection supports strong recommendations to maintain infection prevention and control measures in HCW, and suggests that periodic boosts of SARS-CoV-2 vaccination may be required.

Darunavir/ritonavir (darunavir/r) maintenance strategy, in patients with suppressed HIV RNA viremia, is a potential long-term strategy to avoid nucleoside analogue toxicities and to reduce costs. MONOtherapy Inhibitor protease is a prospective, open-label, noninferiority, 96-week safety and efficacy trial in virologically suppressed patients on triple therapy who were randomized to a darunavir/r triple drug regimen or darunavir/r monotherapy. The primary endpoint was the proportion of patients with HIV RNA less than 400 copies/ml at week 48; treatment failure was defined as two consecutive HIV RNA more than 400 copies/ml (time to loss of virologic response) or any change in treatment. The trial had 80% power to show noninferiority for the monotherapy arm (delta =-10%, 90% confidence interval). A total of 242 patients were screened, 225 of whom were randomized. In the per protocol efficacy analysis, treatment success was 99% on darunavir/r triple drug versus 94% on darunavir/r monotherapy (delta = -4.9%, 90% confidence interval, from -9.1 to -0.8). Similar results were found in intent-to-treat population (92 versus 87.5%, delta = -4.5%, 90% confidence interval from -11.2 to 2.1). Three patients experienced virologic failure on darunavir/monotherapy and none on darunavir/r triple drug. No resistance to protease inhibitor emerged in patients with plasma viral load above 50 copies/ml. The two groups did not differ in the number of serious adverse events. Darunavir/r monotherapy exhibited efficacy rate over 85% with concordant results in the magnitude of difference with darunavir/r triple drug regimen in both intent-to-treat and per protocol analyses, but discordant conclusions with respect to the noninferiority margin. Patients failing on darunavir/r monotherapy had no emergence of new darunavir resistance mutations preserving future treatment options.