Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case-series experience

J Med Virol. 2016 Jul;88(7):1204-10. doi: 10.1002/jmv.24442. Epub 2016 Jan 5.

Abstract

Salvage therapy including foscarnet (PFA), zidovudine (ZDV) and an optimized background ART (OBT) has been shown to be effective in patients with advanced HIV infection, and no therapeutic options. Dolutegravir (DTG) may offer a more active combination. Objective was to describe efficacy and tolerability of PFA-ZDV-DTG containing regimen. In our cohort, we identified patients who: (i) had plasma HIV-1 RNA load (pVL) >50 c/ml (>100 for HIV-2) on combination ART (cART); (ii) had at least 1 PI/r, 1 NRTI, 1 NNRTI (for HIV-1), and at least 1 raltegravir resistance mutations; (iii) were naive to DTG; and (iv) initiated on a PFA-ZDV-DTG containing-regimen with 48 weeks (W48) of follow-up. Out of 5 patients, 2 were infected with HIV-2. At PFA-ZDV-DTG initiation, CD4 cell count was (/mm(3) ) of 64, 40, 10, in HIV-1, and 37, 199, in HIV-2 infected patients; and pVL (log10 c/ml) of 4.8, 5.1, 4.4, in HIV-1, and 3.6, 4.2, in HIV-2 infected patients, respectively. Median OBT genotypic sensitivity score was 1.5 [1-2]. PFA was discontinued in one patient, due to an acute renal failure. At W48, one HIV-1 infected patient had a pVL <50 c/ml and two <200 c/ml; the two HIV-2 infected patients had pVL >100 c/ml. No lack of treatment adherence was observed. In treatment experienced HIV-infected patients, failing cART and without other therapeutic options, a PFA-ZDV-DTG combination therapy could be effective. Renal adverse events should be monitored.

Keywords: HIV; HIV-2; dolutegravir; foscarnet; salvage therapy; zidovudine.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Female
  • Foscarnet / adverse effects
  • Foscarnet / therapeutic use*
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-2 / genetics
  • Heterocyclic Compounds, 3-Ring / adverse effects
  • Heterocyclic Compounds, 3-Ring / blood
  • Heterocyclic Compounds, 3-Ring / therapeutic use*
  • Humans
  • Kidney / drug effects
  • Male
  • Middle Aged
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Salvage Therapy* / adverse effects
  • Viral Load
  • Zidovudine / adverse effects
  • Zidovudine / therapeutic use*

Substances

  • Anti-HIV Agents
  • Heterocyclic Compounds, 3-Ring
  • Oxazines
  • Piperazines
  • Pyridones
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • Foscarnet
  • Zidovudine
  • dolutegravir