Come colpire il reservoir di HIV durante l'infezione acuta? Isabella Abbate, Ph.D. Laboratory of Virology INMI "L. Spallanzani" - Rome - Italy ...

Come colpire il reservoir di HIV durante l’infezione acuta?
                    Il punto di vista del virologo

                     Isabella Abbate, Ph.D.
                     Laboratory of Virology
               INMI “L. Spallanzani” - Rome - Italy

     Dr. I. Abbate has no financial relationships with commercial entities to disclose

Early treatment, HIV Remission, Functional cure

      PLOS Pathogens | www.plospathogens.org 1 March 2013 | Volume 9 | Issue 3 | e1003211

The case of mississipi baby

The rapidity of viral rebound after cART discontinuation is
        associated with the size of HIV reservoir

eLife 2014;3:e03821. DOI: 10.7554/eLife.03821

PLOS ONE | https://doi.org/10.1371/journal.pone.0195514 April 12, 2018

Two phases of HIV DNA decay both more pronuonced in PHI as compared to CHI,
 at the end of follow-up (median of 4 yrs viral suppression) HIV DNA lower in PHI

AIDS 2017, 31:477–484

Timing of reservoir seeding during acute infection:
     from HIV-1 transmission to productive clinical infection

                                                         Modified from Cohen MS et al.
                                                         N Engl J Med 2011

Come colpire il reservoir durante l’infezione acuta?
(Il punto di vista del Virologo)

….con una diagnosi più precoce possibile
nel contesto di una strategia di “Test and treat”
(dallo START study 2015)

HIV diagnosis

Classificazione infezioni acute/recenti secondo Fiebig
          Original article: Fiebig et al. Staging system for primary HIV infection, AIDS 2003

                                                                                            Cumulative duration
                                                                                                       (days)

                                                                                            eclipse: 10 (7-21)
                                                                                            I        7 (13-28)
                                                                                            II       22 (18-34)
                                                                                            III      25 (22-37)
                                                                                            IV       31 (27-43)
                                                                                            V      101 (71-154)

                                                                                            VI      open ended

                    From: McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF
The immune response during acute HIV-1 infection: clues for vaccine development, Nature Reviews Immunology 2010

CID 2018:66 (15 May) •

NAT are not recommended for initial HIV screening because, while they offer a
marginal advantage over fourth generation screening assays in detecting
recent infection, they are not licensed for diagnostic use and may give false-
positive results

Updated January 2018

Pandori ed al: Expert Rev Anti Infect Ther. 2010

Schematic representation of the 30-year evolution of HIV
                 diagnostic assays.

    Thomas S. Alexander Clin. Vaccine Immunol. 2016;23:249-
    253

SIREA Study at INMI L.Spallanzani Rome (0C9 Virology)
                    119 PHI patients from Lug 2013 to Mar 2018 (93%M; mean age 35y; 74.6% MSM)
                                       FII=10, FIII=11, FIV=29, FV=34 and FVI=35.

 At baseline, plasma HIV-1 RNA and HIV-1 DNA showed a similar trend during the different phases of primary infection
with median values higher in early as compared to recent infections. CD4 T cell counts were lower in E as compared to
                     R infections, CD4/CD8 ratio showed no differences between the two groups

AIDS 2015, 29:793–800

The Thai Red Cross AIDS Research Centre anonymous HIV voluntary counseling and testing center
RV254/SEARCH 010 offering immediate ART to patients

                                             Among 74 334 clients screened for HIV infection, HIV
                                             prevalence was 10.9% and the overall incidence of AHI
                                             (N=112) was 2.2 per 100 person-years.
                                             The inclusion of pooled NAT in the testing algorithm increased
                                             the number of acutely infected patients detected, from 81 to
                                             112 (38%), relative to 4thG HIV antigen/antibody immunoassay.

HIV reservoir during the different phases of primary infection

                          Ananworanich et al. Retrovirology 2013, 10:56

Semiannual HIV screening via fourth-generation immunoassay is a better use of
resources than annual pooled NAAT.

Pooled NAAT testing every 12 months of MSM and IDUs in the United States prevents a
modest number of infections, but may be cost-effective given sufficiently high HIV
prevalence levels.

Reduces incidence by 9.6% and costs 92000$ per QALY gained
Remains 4%

However, testing via fourth-generation immunoassay every six months prevents a greater
number of infections, is more economically efficient, and may obviate the benefits of
acute HIV screening via NAAT.

Reduces uncidence by 16% and costs

Point of care test (POC)

  One of the challenges to infectious disease diagnosis in low-resource settings (LRS) is that
  many infections occur far away from centralized laboratories where diagnostic tests are
  routine. Unfortunately, few diagnostic tests can be performed in LRS. In response to the
  need for improved diagnostic tests for the developing world, the World Health Organization
  (WHO) Sexually Transmitted Diseases Diagnostics Initiative (SDI) has identified
  appropriate diagnostic test attributes to address disease control needs for LRS.
  These attributes, refered to as the “ASSURED” criteria can be summarized as: sensitive,
  specific, user-friendly, rapid and robust, equipment-free and deliverable to end-users.

4° Gen POC

                                                                       PLOS ONE | DOI:10.1371/ 2016

             Fitzgerald N, et al. Sex Transm Infect 2017;93:100–101.

NAT POC

Cobas Liat Roche

                        GeneXpert® HIV-1
                        Qual assay

       SAMBA HIV qualitative Test

PLOS ONE | DOI:10.1371/journal.pone.0113693 November 26, 2014
    NAT POC

        Non-instrumented nucleic acid
       amplification (NINA) devices that
      generate heat from the exothermic
     reaction of calcium oxide and water

For a recent review on miniaturized devices for POC molecular detection of HIV see:
Mauk et al Lab Chip 2017, 17:382.

Journal of the International AIDS Society 2017, 20: 21579