Prevention and control of HIV/AIDS in China: lessons from the past three decades.

ABSTRACT: In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Pre-S deletions of hepatitis B virus predict recurrence of hepatocellular carcinoma after curative resection.

The relationship between hepatitis B virus (HBV) and the prognosis of hepatocellular carcinoma (HCC) after surgery remains uncertain. A retrospective cohort study was performed to evaluate the impact of pre-S deletions, T1762/A1764, and A1896 mutations on prognosis of HCC after curative resection. A total of 113 patients with positive serum HBV DNA (>200 IU/mL) who had underwent curative resection of pathologically proven HCC were recruited to determine the risk factors affecting the prognosis.The median follow-up time was 36.5 months and recurrence was detected in 67 patients (59.3%). The cumulative recurrence rates and overall survival rates at 1-, 3-, and 5-year after curative resection were 18.0%, 49.7%, 70.3%, and 93.7%, 61.0%, 42.5%, respectively. Patients with pre-S deletions showed significantly higher recurrence rates compared with those with wild type infection (HR: 1.822, P = .018), but not related with a significantly poor survival (HR: 1.388, P = .235). Subgroup analysis indicated that the patients with type III deletion had significant higher tumor recurrence rates than other deletion types (HR: 2.211, 95% confidence intervals [CI]: 1.008-4.846, P = .048). Multivariate analysis revealed that pre-S deletion, tumor size >3 cm in diameter, and the presence of microvascular invasion were independent risk factors for tumor recurrence. HBV pre-S deletions were found to be clustered primarily in the 5' end of pre-S2 region and were more often found between amino acids 120 and 142 of the pre-S2 domain. The domains most frequently potentially involved were the transactivator domain in pre-S2 and polymerized human serum albumin binding site.Our cohort showed that pre-S deletions at the time of resection could predict tumor recurrence in HCC patients after curative resection.

Transcriptomic analysis of peripheral blood mononuclear cells in rapid progressors in early HIV infection identifies a signature closely correlated with disease progression.

BACKGROUND: A substantial percentage (10%-15%) of HIV-infected individuals experience a sharp decline in CD4(+) T-cell counts and progress to AIDS quickly after primary infection. Identification of biomarkers distinguishing rapid progressors (RPs) vs chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy. METHODS: mRNA and microRNA (miRNA) expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111 (22) days [mean (SD)] of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by ROC analysis and Kaplan-Meier survival analysis. RESULTS: Pathway enrichment analysis showed that genes with deregulated expression in RPs were primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a, and -503) in RPs were significantly decreased compared to those in CPs (P < 0.05). The decreased expression of these miRNAs was associated with a rapid disease of progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray analysis converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival. CONCLUSIONS: Our results have identified a distinct transcriptomic signature in PBMCs of RPs and provided novel insights to the pathogenesis of HIV infection.

Identification and characterization of broadly cross-reactive neutralizing antibodies in patients infected with HIV-1 B'/C recombinant (CRF07_BC).

The identification of broadly cross-reactive neutralizing (BCN) antibodies is essential for the development of a more universally effective vaccine for human immunodeficiency virus (HIV). In this study, CRF07_BC serum was analyzed for cross-clade antibody reactivity and neutralization. A total of 117 HIV-1 sera (CRF07_BC) were screened for their capacity to neutralize three primary HIV-1 isolates. A total of 18 out of 117 sera cross-neutralized all three viruses, and were tested along with eight randomly selected non-BCN sera against seven primary HIV-1 isolates and two laboratory strains that represented different clades and tropisms. BCN sera neutralized eight or all nine of these primary isolates. Non-BCN sera did not display any broadly cross-reactive neutralizing responses. BCN sera neutralized with higher frequency and geometric mean titers compared to non-BCN sera. Sera from asymptomatic individuals on average neutralized a significantly greater number of the three key isolates than sera from symptomatic individuals. Our data indicate that the three HIV-1 isolated strains are sufficient to screen broad cross-neutralizing sera, and that BCN responses may contribute to protection from infection and disease progression. The neutralizing antibody response demonstrated extensive cross-neutralization, suggesting that neutralizing antibodies induced by vaccines will have a relatively low epitope diversity to overcome in patients infected with HIV-1 B'/C recombinant (CRF07_BC).

R-848 triggers the expression of TLR7/8 and suppresses HIV replication in monocytes.

BACKGROUND: Toll-like receptors (TLR) 7 and 8 are important in single-stranded viral RNA recognition and may play a role in HIV infection and disease progression. We analyzed TLR7/8 expression and signaling in monocytes from HIV-infected and uninfected subjects to investigate a pathway with new potential for the suppression of HIV replication. METHODS: Eighty-one HIV-infected and uninfected subjects from Liaoning and Henan provinces in China participated in this study. Monocytes were isolated from subjects' peripheral blood mononuclear cells by magnetic bead selection. TLR7 and TLR8 mRNA was measured using quantitative real-time reverse transcriptase PCR. R-848 (resiquimod) was used as a ligand for TLR7 and TLR8 in order to 1) assess TLR7/8-mediated monocyte responsiveness as indicated by IL-12 p40 and TNF-α secretion and 2) to examine HIV replication in cultured monocytes in the presence of R-848. RESULTS: We found that expression of TLR7/8 mRNA in peripheral blood monocytes decreased with disease progression. TLR7 expression was decreased with stimulation with the TLR7/8 agonist, R-848, in vitro, whereas TLR8 expression was unaffected. Following R-848 stimulation, monocytes from HIV-infected subjects produced significantly less TNF-α than those from uninfected subjects, but trended towards greater production of IL-12 than stimulated monocytes from uninfected subjects. R-848 stimulation also suppressed HIV replication in cultured monocytes. CONCLUSIONS: Our study provides evidence that the TLR7 and TLR8 triggering can suppress HIV replication in monocytes and lead to postpone HIV disease progression, thereby offering novel targets for immunomodulatory therapy.

[Resistance to HIV-1 infection of CD4 + T lymphocytes in vitro from chinese HIV-1 exposed seronegative individuals].

OBJECTIVE: To determine the relative resistance to HIV-1 infection of CD4 + T lymphocytes in HIV-exposed seronegative individuals (ESNs) in China. METHODS: HIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4 + T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4 + T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks. RESULTS: For M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P < 0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups (P > 0.05). CONCLUSION: CD4 + T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.