ABSTRACT
HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differentiation, with enrichment of several molecules associated with HIV infection susceptibility, longevity and self-renewing capacities. These protein profiles are enriched in a fraction of CD4+TRM expressing CD32. Cervical explant models show that CD4+TRM preferentially support HIV infection and harbor more viral DNA and protein than non-TRM. Importantly, cervical tissue from ART-suppressed HIV+ women contain high levels of viral DNA and RNA, being the TRM fraction the principal contributor. These results recognize the lower female genital tract as an HIV sanctuary and identify CD4+TRM as primary targets of HIV infection and viral persistence. Thus, strategies towards an HIV cure will need to consider TRM phenotypes, which are widely distributed in tissues.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , Immunologic Memory/immunology , Adult , Aged , Anti-Retroviral Agents/therapeutic use , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/virology , Cervix Uteri/drug effects , Cervix Uteri/virology , Disease Reservoirs/virology , Female , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Humans , Middle Aged , Mucous Membrane/drug effects , Mucous Membrane/virology , Viral Load/drug effects , Viral Load/genetics , Viral Load/immunologyABSTRACT
OBJECTIVE: To demonstrate our experience with hysteroscopic assistance in the laparoscopic repair of an isthmocele. DESIGN: Surgical video article (Canadian Task Force classification III). SETTING: University hospital. INTERVENTION: A 42-year-old woman with a history of previous caesarean section presented as an emergency with a large, seriously infected isthmocele. Once the infection was cured with antibiotics, sonography revealed a 23 × 14-mm isthmocele with 1.4-mm residual myometrium thickness. She reported postmenstrual spotting and dysmenorrhea of several years duration, as well as previous dyspareunia that had worsened after her cesarean section. Given her symptomatic isthmocele with thin residual myometrium and desire for childbearing, laparoscopic repair was offered. First, the bladder was dissected to expose the isthmus. Uterine arteries were dissected. Hysteroscopic guidance and transillumination revealed the edges of the defect. The isthmocele and fibrotic tissue were excised with cold scissors, minimizing cauterization. A hysterometer was placed in the uterine cavity to respect the cervical canal and posterior uterine wall, and the myometrium was then closed in 2 layers. The total surgical time was 120 minutes. The postoperative period was uneventful. At 2 months after surgery, sonography confirmed restoration, with a myometrium thickness of 8.3 mm. The patient was asymptomatic, except for dyspareunia. At 6 months after surgery, hysteroscopic examination was normal. We recommended that the patient avoid attempting pregnancy for 9 months. CONCLUSION: Hysteroscopic simultaneous assistance during laparoscopic isthmocele repair can be of great help in identifying the edges of the defect, especially in large cavities and in first cases, in which edges might not be clear otherwise. Resecting all of the fibrotic tissue while respecting healthy myometrium is essential. Excessive cauterization and ischemic suturing could prevent proper healing of the myometrium.
