Occurrence of the S230R integrase strand inhibitor mutation in a treatment-naïve individual case report.

RATIONALE: Transmitted resistance to integrase strand inhibitors (INSTI) has been uncommon, but is slowly becoming more prevalent among those living with HIV. In an era with 2-drug regimens for antiretroviral therapy, transmitted resistance for INSTI is alarming. PATIENT CONCERNS: A 28-year-old African American female was recently diagnosed with HIV during a 30-week prenatal visit. DIAGNOSIS: HIV 4th generation test was positive as well as confirmation. Genotype was performed using next generation sequencing. INTERVENTIONS: Patient was initially rapidly started on a dolutegravir based regimen and changed to a protease inhibitor regimen once her genotype reported an S230R mutation. OUTCOMES: Patient became virally suppressed on antiretroviral therapy and delivered an HIV negative baby. LESSONS: INSTI resistance testing should be done for treatment-naïve and INSTI-naïve persons, particularly when considering 2 drug INSTI based regimens.

Evaluation of anti-HBV drug resistant mutations among patients with acute symptomatic hepatitis B in the United States.

BACKGROUND & AIMS: Reported HBV drug resistance mutations among previously untreated patients with chronic hepatitis B are variable. Whether resistant HBV strains are transmitted in the acute setting is uncertain. We sought to document the presence of antiviral resistance (AVR) mutations in patients with acute HBV (AHB) infection. METHODS: AHB infection was defined by HBsAg/IgM anti-HBc positivity, ALT>10X ULN and compatible clinical history. The TRUGENE HBV kit was used to perform genotyping and direct sequencing of the viral polymerase. INNO-LiPA HBV DRv2 and DRv3 were used to detect AVR mutations. Clonal sequencing was conducted on selected specimens. RESULTS: Twenty-three patients were evaluated (mean age, 43 years; 54% male; 39% African American, 39% Caucasian, 13% Hispanic and 4% Asian). The mean peak ALT was 1554.2IU/L and mean peak total serum bilirubin was 12 mg/dl. The HBV DNA median viral load (N = 15) was 5.14 log(10)IU/ml. Nineteen patients were genotype A, and 1 each were genotype C, D, E and G. HBV drug resistance mutations were not detected by direct sequencing or INNO-LiPA. Clonal sequencing was conducted on 192 clones isolated from three patients and showed rtA181T, rtM250V and rtS202G mutations at an overall frequency of 1.54%, 1.39%, and 1.67% respectively. CONCLUSIONS: We detected adefovir/lamivudine and entecavir relevant mutations in a minor population (<2%) of viral clones by clonal sequencing only. The clinical significance of these mutations is uncertain and may represent small populations of quasi-species vs. transmission of drug resistant strains.

Late presentation and transmitted drug resistance mutations in new HIV-1 diagnoses in Detroit.

OBJECTIVE: To characterize the epidemiology and transmitted drug resistance mutation (TDRM) patterns among individuals with newly diagnosed HIV-1 infection seen at Henry Ford Hospital in Detroit from 2006 to 2008. METHODS: This was a retrospective analysis of medical records from individuals aged ≥ 18 years with a new diagnosis of HIV-1 infection. Individuals who underwent genotypic resistance testing were included in the study. RESULTS: One hundred thirty-three individuals were included; 99 (74%) were males, 104 (78%) were African-Americans, and 61 (46%) had a CD4+ count of ≤ 200 cells/µl. The prevalence of TDRM was 17% (23/133). Non-nucleoside reverse transcriptase mutations occurred in 11 (8%), nucleoside reverse transcriptase mutations in 13 (10%), and protease inhibitor mutations in 10 (8%). CD4+ count >350 cells/µl and HIV viral load on presentation were associated with TDRM in the multivariate analysis (p=0.004 and p<0.001 respectively). CONCLUSIONS: Late diagnosis of HIV-1 and transmitted antiretroviral resistance are relatively common in Detroit. While most newly diagnosed persons were candidates for antiretroviral therapy on presentation, the high prevalence of TDRM has significant implications in the selection of first-line highly active antiretroviral therapy (HAART).