Journal of Immunology Research

Review Article

HIV-Related Immune Activation and Inflammation: Current Understanding and Strategies

Table 1

Current Interventions for HIV-related Immune Activation and Inflammation.


Drug	Main inclusion criteria/groups	Case/control	Dose	Country	Efficiency/mechanism	Reference

Immunosuppressive drug
Prednisolone	cells/μL, absence of AIDS-defining symptoms, ART-naïve patients	Prednisolone ()/placebo ()	5 mg, po, qd, 2 years	Tanzania & Germany	sCD14 ↓, CD38/HLA-DR/CD8⁺ ↓, CD4 count ↑, HIV viral load ↑	[78]
Prednisolone	5 groups: (1) HIV-1 subjects untreated; (2) HIV-1 subjects treated with prednisolone; (3) HIV-1 with ART; (4) HIV-1 with ART+ prednisolone; (5) elite controllers	Untreated (); prednisolone (); ART (); prednisolone+ART (); elite controllers ()	5 mg/day	Germany	CD38⁺CD8⁺% ↓, CD38⁺CD4⁺% (-), sCD14 ↓, LPS-binding protein (LBP) ↓, ART group vs. ART+prednisolone group: CD38⁺CD8⁺% (-), D38⁺CD4⁺% (-), sCD14 (-), LBP (-)	[76]
HCQ	ART-treated HIV patients, cells/L during the last 12 months of therapy, HIV RNA copies/mL	Prior/posttreatment ()	400 mg/day, 6 w	Italy	Ki67CD4% ↓, CD69CD14% ↓; IL-6/TNFα ↓, Tregs↑, IFN-α secreting plasmacytoid DC ↓; LPS/TLR-mediated immune activation ↓; HLADRII, CD69, and CD38/CD45RO CD8 T% ↓	[84]
HCQ	18 to 65 years, naive to ART or no therapy in the previous 12 months; CD4⁺ cells/μL, copies/mL	HCQ ()/placebo ()	400 mg, 48 w	UK	CD8⁺ T cell activation (-), CD4⁺ T cell activation (-), D-dimer (-), IL-6 (-), Ki67⁺CD4, Ki67⁺CD8, CD4 cell count ↓	[85]
CQ	Off-ART (arms A and B): HIV-1-infected; on-ART (arms C and D) participants: months, copies/mL, CD4 cell cells/μL	Arm A (); arm B () Arm C (); arm D ()	Arms A and C: CQ (250 mg,12 w)/placebo (12 w); arms B and D: placebo (12 w)→CQ (250 mg, 12 w)	US	On-ART cohort: HLA-DR⁺CD8⁺ ↓, CD38⁺CD8⁺ ↓, IP10 ↓	NCT00819390
Cyclosporine	Primary HIV infection (HIV-1 antibody negative, HIV-1 RNA positive in plasma, and ≥3 bands in western blot)	CsA+ART (), ART ()	0.3-0.6 mg/kg po, q12 h, 8 w	Switzerland, Italy	CsA+HAART constantly maintained higher levels of CD4+ T cells; week 48: HIV-1-specific IFN-γ-secreting CD4 T% is higher than ART alone cohort	[91]
TwHF	years, plasma HIV-1 copies/mL and suboptimal CD4 cell recovery	INRs ()/inadequate responders ()	10 mg, po, tid, 12 months	China	Both groups: CD4 T cell count ↑, CD38⁺HLA-DR⁺CD8 T cell% ↓, CD38⁺HLA-DR⁺CD4 T cell% ↓	[104]
Stains
Atorvastatin	No ART, CD4⁺/μL, HIV-1 copies/mL, mg/dL	Atorvastatin ()/control ()	80 mg, qd, 8 w	US	CD4⁺HLA-DR⁺% ↓; CD8⁺HLA-DR⁺% ↓; CD8⁺HLA-DR⁺CD38⁺ T cells% ↓, CD4T (-), CD4⁺HLA-DR⁺CD38⁺ T cells% (-), CD4⁺CD38⁺% (-), CD8⁺CD38⁺% (-) TC ↓, LDL ↓	[105]
Rosuvastatin	ART months, HIV-1 copies/mL, LDL mg/dL; mg/L and/or expression of CD38 and HLA-DR antigens ≥19% of CD8⁺ T cells at screening	Statin ()/placebo ()	10 mg, po, qd	US	hsCRP, IL-6, sTNFR-I/II, IP10 and D-dimer (-) Lp-PLA2 level ↓; DL cholesterol level ↓
Treatment on microbial translocation
Probiotic	Women, 18–45 years, not-normal vaginal microbiota, no ART (CD4 cells/μL)	Probiotics ()/placebo ()	Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 ( colony forming units), bid, 25 w	London, Netherlands	Insignificant changes in the immune parameters IFN-γ, IL-10, IgG, and IgE	[110]
Synbiotic dietary supplement	Adult females, currently taking ART, CD4 cells/μL	Synbiotic ()/fiber group ()	SynBiotic 2000®, fibers, qd, 4 w	USA	DR⁺38-PD1-CD4% ↓, CD38⁺CD8⁺ T cells ↓, CD38, HLA-DR, PD-1% on CD4 or CD8(-), monocyte activation (-); CRP (-)	[112]
Probiotics	18-80 years, without history of drug failure	Probiotics ()/healthy donors ()	1 g(a), 48 w	Italy	CD4⁺CD38⁺HLA-DR⁺ T cell ↓, CD8⁺CD38⁺HLA-DR⁺ T cells ↓, IL6 ↓, CRP ↓, sCD14 (-), D-dimer (-)	[109]
Recombinant lactoferrin	≥ 40 years, year, HIV RNA copies/mL	A rhlactoferrin then placebo sequence (A-P, ), placebo then rhlactoferrin (P-A, )	A-P: M1-3 rhlactoferrin,1500 mg bid, M5-8 placebo P-A: M1-3 placebo, M5-8 rhlactoferrin,1500 mg bid	US	sCD163 ↓, IL-6 (-), D-dimer (-), sCD14 (-), CD8⁺PD1⁺% (-), CD8⁺KI67⁺% (-), D8⁺CD38⁺HLADR⁺% (-), CD4⁺PD1⁺% (-), CD4⁺KI67⁺% (-), CD4⁺CD38⁺HLADR⁺% (-)	[116]
Synbiotics	18-65 years, ART-naïve (stage A or B), CD4 cells/μL	Probiotic (), synbiotic (), prebiotic (), placebo ()	Lactobacillus rhamnosus HN001+Bifidobacterium lactis Bi-07 at 10⁹ cfu/mL as probiotics, 10 g of agave inulin as prebiotic, and the combination of both as symbiotic	Mexico	IL-6 ↓, TNF-α (-), IL-1β (-), IL-10 (-)	[113]
Hypoglycemic agents
Metformin	years, year on ART, HIV copies/mL	Metformin ()/control ()	Metformin 500 mg, 24 w	Hawaii	PD1⁺ ↓, PD1⁺TIGIT⁺ ↓, PD1⁺TIGIT⁺TIM3⁺CD4 T ↓	[119]
Sitagliptin	cART for the prior 6 months, CD4⁺ T cell cells/μL, HIV copies/mL	Sitagliptin 100 mg/d ()/placebo ()	100 mg, qd, 8 w	US	hsCRP ↓, CXCL10 ↓, CD4⁺/CD8⁺ ratio (-), D-dimer (-), IL-6 (-)	[122]
Other drugs
Aspirin	ART for ≥48 w, HIV RNA below quantification limit for ≥48 w	HIV ()/control ()	Aspirin: 81 mg, clopidogrel: 75 mg 24 w	US	sCD14 ↑, sCD163 (-), D-dimer (-), sTNFR1 (-), sTNFR2 (-), sIL-6 (-), thrombogenicity (-), sCD14 (-)	[124]
Celecoxib	18–65 years, asymptomatic, HIV-1-positive patients off ART (HIV copies/mL, CD4⁺ T cell cells/μL)	Celecoxib arm ()/control arm ()	400 mg, bid, 12 w	Norway	CD38⁺CD8⁺ T% ↓, IgA ↓, a combined score for inflammatory markers ↓, PD-1⁺CD8⁺ T% ↓, CD3⁺ CD4⁺ CD25⁺ CD127^low/− Treg ↑	[125]
Cannabis	HIV-1-infected ART-treated participants	Control () Moderate () Heavy ()	Moderate (cannabis: 5.1-69.9 μg/L), heavy users (cannabis: ≥70 μg/L)	USA	HLA-DR⁺CD38⁺CD4% ↓, HLA-DR⁺CD38⁺CD8% ↓, CD14⁺⁺CD16^-% ↑, CD11c⁺CD123^– ↓	[129]
Pyridostigmine	No ART, D4 T cell /μL	Pyridostigmine ()/placebo ()	30 mg tid, 1 w	Mexico	CD69CD4 ↓, Treg ↑, T cell proliferation ↓, IFN-γ ↓, TNF ↓, IL4/5/10 ↑	[131]
Lisinopril	HIV -75 copies/mL, CD4⁺ cells/μL in INRs and ≥350 cells/μL in IRs	Lisinopril ()/placebo ()	Lisinopril 20 mg, 24 w	US	CD38⁺HLA-DR⁺ CD4⁺ (-), CD38⁺HLA-DR⁺ CD8⁺ (-)

VL: viral load; INRs: immunologic nonresponders; IRs: immunologic responders; LDL: low-density lipoprotein.