Clinical and Biological Factors Associated With Early Epstein-Barr Virus Infection in Human Immunodeficiency Virus-Exposed Uninfected Infants in Eastern Uganda.

BACKGROUND: Immune control of Epstein-Barr virus (EBV) infection is impaired in individuals with HIV. We explored maternal factors associated with EBV acquisition in HIV-exposed uninfected (HEU) infants and the relationship between EBV infection and serious adverse events (SAEs) during the first year of life. METHODS: 201 HEU infants from Uganda enrolled in the ANRS 12174 trial were tested for antiviral capsid antigen (anti-VCA) antibodies at week 50. Date of infection was estimated by testing EBV DNA at weeks 1, 6, 14, 26, 38, and 50 postpartum on dried blood spots. RESULTS: Eighty-seven (43%) infants tested positive for anti-VCA IgG at week 50. Among the 59 infants positive for EBV DNA, 25% were infected within the first 26 weeks. Almost half (12%) were infected before week 14. Shedding of EBV in breast milk was associated with EBV DNA in maternal plasma (P = .009), HIV RNA detection (P = .039), and lower CD4 count (P = .001) and correlated with plasma EBV DNA levels (P = .002). EBV infant infection at week 50 was associated with shedding of EBV in breast milk (P = .009) and young maternal age (P = .029). Occurrence of a clinical SAE, including malaria and pneumonia, was associated with higher levels of EBV DNA in infants (P = .010). CONCLUSIONS: By assessing EBV infection in HEU infants we observed that infection during the first year is determined by HIV and EBV maternal factors and that EBV DNA levels were higher among infants with clinical SAEs. CLINICAL TRIALS REGISTRATION: NCT00640263.

Once-daily etravirine/raltegravir (400/800 mg q24h) dual therapy maintains viral suppression over 48 weeks in HIV-infected patients switching from a twice-daily etravirine/raltegravir (200/400 mg q12h) regimen.

BACKGROUND: Etravirine/raltegravir dual therapy has been shown to be highly effective as a twice-daily (q12h) regimen in suppressed HIV-infected patients enrolled in the ANRS-163 study. OBJECTIVES: As a once-daily (q24h) regimen is easier for daily life, we aimed to evaluate the capacity of etravirine/raltegravir (400/800 mg) q24h to maintain viral suppression in patients on etravirine/raltegravir q12h. METHODS: Patients on a suppressive etravirine/raltegravir q12h regimen for at least 96 weeks were switched to etravirine/raltegravir q24h in this prospective, multicentre, open-label, single-arm study. Primary outcome was the rate of virological failure (VF: confirmed pVL >50 copies/mL, single pVL >400 copies/mL or single pVL >50 copies/mL with ART change) at Week 48 (W48). Secondary outcomes included treatment strategy success rate (no VF and no treatment discontinuation), regimen tolerability, plasma drug concentrations and resistance profile in the case of VF. RESULTS: A total of 111 patients were enrolled, with a median (IQR) age of 57 years (52-62), CD4 count of 710 cells/mm3 (501-919) and viral suppression for 7.9 years (5.9-10.7). Two patients experienced viral rebound at W24 and W48, leading to a VF rate of 2.0% (95% CI 0.5-7.8) at W48, associated with INSTI resistance in one case. Both had past NNRTI mutations. Ten patients discontinued treatment for adverse events (n = 2), investigator or patient decisions (n = 3), lost to follow-up (n = 3), death (n = 1) or pregnancy (n = 1). Overall, the strategy success rate was 89% (95% CI 81.5-93.6) at W48. In a subgroup of 64 patients, median (IQR) plasma C24h concentrations were 401 ng/mL (280-603) for etravirine and 62 ng/mL (31-140) for raltegravir. CONCLUSIONS: Switching patients virally suppressed on etravirine/raltegravir q12h to the same regimen but given q24h was highly effective in maintaining virological suppression in HIV-infected patients.

Chemsex in HIV pre-exposure prophylaxis users: Assessment of mood disorders and addictive behavior.

The assessment of mood disorders and addiction linked to the practice of chemsex is of interest given the psychoactive substances used. The aim of this study was to assess risky sexual and addictive behavior to chemsex and related anxiety/depression symptoms in individuals receiving HIV pre-exposure prophylaxis (PrEP). In this cross-sectional study, all adults presenting for PrEP renewal at French sexual health centers were enrolled from January 2018 to March 2019. Participants completed a questionnaire on chemsex (i.e., the use of psychoactive substances before/during sex), including adapted Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to chemsex addiction (questions of ASSIST were modified to focus on chemsex). Anxiety/depression was assessed with the Hospital Anxiety and Depression Scale. In the last 3 months before enrollment, 39.8% (94/236) of participants reported chemsex. The main psychoactive substances consumed during chemsex were cathinones (74.6%), gamma-hydroxybutyrate (66.3%), and other psychostimulants (60%). The median score of the chemsex-focused ASSIST was 8 [IQR25-75 : 3-15]; 72.2% of participants had a score justifying at least a brief intervention (>4). In multivariate analyses, anxiety and cathinones consumption were associated with an ASSIST score >4: OR 13.65 (95% CI 1.68-662.7), P = 0.0062, and OR 8.468 (95% CI 2.066-43.059), P = 0.0014, respectively. The level of addiction to the practice of chemsex can be difficult to estimate for the user, and the ASSIST makes it possible to evaluate this addiction and to direct the subjects toward specialized consultations of addictology, sexual health, or PrEP renewals. The implementation of the modified ASSIST in these consultations can allow early systematic screening and counseling.

Tenofovir nephrotoxicity: 2011 update.

Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir is widely used to treat HIV infection and approved for treatment of hepatitis B virus. Despite initial cell culture and clinical trials results supporting the renal safety of tenofovir, its clinical use is associated with a low, albeit significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction that may be associated with acute kidney injury or chronic kidney disease. Withdrawal of the drug leads to improvement of analytical parameters that may be partial. Understanding the risk factors for nephrotoxicity and regular monitoring of proximal tubular dysfunction and serum creatinine in high-risk patients is required to minimize nephrotoxicity. Newer, structurally similar molecular derivatives that do not accumulate in proximal tubules are under study.