Long acting antiretroviral drugs represent a promising approach for chronic treatment of HIV infection. Here, we study the efficacy and safety of albuvirtide (ABT), an HIV-1 fusion inhibitor with a half life of 11–12 days in human. ABT was evaluated in a 7-week, open-label and randomized trial, combining with LPV/r. Twenty HIV-1-infected adults were assigned to two dose groups, receiving ABT (160 or 320 mg) given weekly and LPV/r given twice daily. At week 7, the decline of HIV-1 RNA from baseline was 1.9 (1.3–2.3) log10 and 2.2 (1.6–2.7) log10 copies/ml, and suppression of HIV-1 RNA to below 50 copies/ml was achieved in 11.1 % (1/9) and 55.6 % (5/9) patients, for the 160 and 320 mg dose group respectively. A clear dose-efficacy correlation of ABT was demonstrated. ABT combining with LPV/r is a promising two-drug regimen to be tested in larger patient population.

A rapidly escalating outbreak of syphilis infection has been affected men who have sex with men, particularly those with HIV-1 infection. γδ T cells are unconventional immune cells with two main subsets, Vδ1 T cells and Vδ2 T cells, which possess a combination of innate and adaptive immune features allowing them to against HIV. However, whether syphilis infection affects the phenotype and function of γδ T cells in HIV-1-infected patients remains unclear, especially in acute HIV-1 infection (AHI). In this study, we enrolled 57 HIV-1-infected patients (24 with HIV-1 infection only and 33 co-infected with syphilis) from an acute HIV-1-infected cohort in Beijing (PRIMO). A comprehensive analysis of γδ T-cell phenotype and function was performed by flow cytometry. We found syphilis co-infection could reverse the imbalance of Vδ1/Vδ2 ratio in AHI. Syphilis infection results in decreased γδ T-cell activation in AHI, but increased γδ T-cell activation in chronic HIV-1 infection (CHI). Moreover, patients with CHI had larger numbers of IL-17-producing γδ T cells than those with AHI, regardless of syphilis status. Thus, syphilis affected the γδ T-cell immune response differently in patients depending on the stages of HIV-1 disease. In addition, the percentage of IL-17-producing γδ T cells was positively correlated with the percentage of neutrophils. These results suggest that the γδ T-cell/IL-17/neutrophil axis is involved in HIV-1 pathogenesis and disease progression. Taken together, our observations provide new insight into the roles of γδ T cells in immunopathogenesis of syphilis and HIV co-infection, particularly during AHI, and our findings may be helpful for the prevention of syphilis and other sexually transmitted infections and highlight the great significance on the remedy of patients co-infected with HIV.

Bw4 homozygosity in human leukocyte antigen class B alleles has been associated with a delayed acquired immunodeficiency syndrome (AIDS) development and better control of human immunodeficiency virus type 1 (HIV-1) viral load (VL) than Bw6 homozygosity. Efficient CD8 T cell and natural killer (NK) cell functions have been described to restrain HIV-1 replication. However, the role of KIR3DL1 expression on these cells was not assessed in Bw4-homozygous participants infected with HIV-1 CRF01_A/E subtype, currently the most prevalent subtype in China. Here, we found that the frequency of KIR3DL1-expressing CD8 T cells of individuals homozygous for Bw6 [1.53% (0–4.56%)] was associated with a higher VL set point (Spearman r_s = 0.59, P = 0.019), but this frequency of KIR3DL1⁺CD8⁺ T cells [1.37% (0.04–6.14%)] was inversely correlated with CD4 T-cell count in individuals homozygous for Bw4 (r_s = −0.59, P = 0.011). Moreover, CD69 and Ki67 were more frequently expressed in KIR3DL1⁻CD8⁺ T cells in individuals homozygous for Bw4 than Bw6 (P = 0.046 for CD69; P = 0.044 for Ki67), although these molecules were less frequently expressed in KIR3DL1⁺CD8⁺ T cells than in KIR3DL1⁻CD8⁺ T cells in both groups (all P < 0.05). KIR3DL1⁻CD8⁺ T cells have stronger p24-specific CD8⁺ T-cell responses secreting IFN-γ and CD107a than KIR3DL1⁺CD8⁺ T cells in both groups (all P < 0.05). Thus, KIR3DL1 expression on CD8 T cells were associated with the loss of multiple functions. Interestingly, CD69⁺NK cells lacking KIR3DL1 expression were inversely correlated with HIV-1 VL set point in Bw4-homozygous individuals (r_s = −0.52, P = 0.035). Therefore, KIR3DL1⁻CD8⁺ T cells with strong early activation and proliferation may, together with KIR3DL1⁻CD69⁺NK cells, play a protective role during acute/early HIV infection in individuals homozygous for Bw4. These findings highlight the superior functions of KIR3DL1⁻CD8⁺ T cells and KIR3DL1⁻CD69⁺NK cells being a potential factor contributing to delayed disease progression in the early stages of HIV-1 infection.

Human leukocyte antigen (HLA)-B*5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*5701 prevalence in HIV-1-infected subjects in China. We investigated HLA-B*5701 prevalence in HIV-1-infected population including Han and non-Han ethnic groups. A prospective multi-centre study was designed to determine status of HLA-B*5701 in HIV-1-infected adults at six sites across China. HLA-B*5701 was tested by the method of PCR-SSP. From six centers, 3,000 HIV-infected patients [2,452 (81.7%) Han, 548 (18.3%) Non-Han] were recruited with a mean age of 36.7 years old. The overall HLA-B*5701 prevalence was 0.86% [95% confidence interval (CI) 0.55–1.26%]. The prevalence of HLA-B*5701 among Han subjects was similar to that among non-Han subjects, which was 0.88% (95% CI 0.54–1.34%) and 0.76% (95% CI 0.19–1.93%), respectively (p value = 0.787). There were no differences in prevalence of HLA-B*5701 between subjects born in Henan, Yunnan, Shanxi, Guangdong, Hebei, Beijing and other provinces (p = 0.999). HLA-B*5701 prevalence is very low in HIV-infected Chinese subjects, both in the Han and Non-Han nationalities. And there are no differences among different birthplaces across China.

HIV is an immunodeficiency disease with emergence of inadequate corresponding reconstruction therapies. Pyroptosis of CD4+T cell is mainly caused by immune activation and inflammation that cannot be reduced by successful antiretroviral therapy (ART) alone. Co-infections because of CD4+T cell reconstitution failure can occur. Anti-inflammatory treatment determines the success of immune reconstitution. In our experiment, only a few cytokines could recover to normal level following with a 2-year antiretroviral treatment in early ART initiation, which is consistent with current findings about adjuvant HIV anti-inflammatory therapy. Early infection is often accompanied by a more severe inflammatory response. Innate immunity cytokines like GM-CSF, IP-10, and TNF-α exhibited the most elevated levels among all kinds of inflammatory cytokines. The correlation analysis showed at least eight cytokines contributing to the changes of CD4/CD8 ratio.