Incomplete immune reconstitution remains a global challenge for human immunodeficiency virus (HIV) treatment in the present era of potent antiretroviral therapy (ART), especially for those individuals referred to as immunological non-responders (INRs), who exhibit dramatically low CD4 + T-cell counts despite the use of effective antiretroviral therapy, with long-term inhibition of viral replication. In this review, we provide a critical overview of the concept of ART-treated HIV-positive immunological non-response, and also explain the known mechanisms which could potentially account for the emergence of immunological non-response in some HIV-infected individuals treated with appropriate and effective ART. We found that immune cell exhaustion, combined with chronic inflammation and the HIV-associated dysbiosis syndrome, may represent strategic aspects of the immune response that may be fundamental to incomplete immune recovery. Interestingly, we noted from the literature that metformin exhibits properties and characteristics that may potentially be useful to specifically target immune cell exhaustion, chronic inflammation, and HIV-associated gut dysbiosis syndrome, mechanisms which are now recognized for their critically important complicity in HIV disease-related incomplete immune recovery. In light of evidence discussed in this review, it can be seen that metformin may be of particularly favorable use if utilized as adjunctive treatment in INRs to potentially enhance immune reconstitution. The approach described herein may represent a promising area of therapeutic intervention, aiding in significantly reducing the risk of HIV disease progression and mortality in a particularly vulnerable subgroup of HIV-positive individuals.
Humans ; Immune Reconstitution ; CD4 Lymphocyte Count ; Metformin/therapeutic use* ; Dysbiosis ; Antiretroviral Therapy, Highly Active ; HIV Infections/drug therapy* ; CD4-Positive T-Lymphocytes ; HIV ; Syndrome

Objective:To assess the efficacy and safety of trimethoprim/sulfamethoxazole (TMP/SMZ) combined with caspofungin for the treatment of acquired immunodeficiency syndrome (AIDS)patients with moderate to severe pneumocystis pneumonia (PCP) requiring mechanical ventilation.Methods:The clinical data of AIDS patients who admitted to Chongqing Public Health Medical Center from March 1, 2019 to March 1, 2021 with moderate to severe PCP requiring mechanical ventilation were retrospectively analyzed. Clinical characteristics and outcomes were compared between two groups receiving either combination therapy with TMP/SMZ and caspofungin (combination therapy group) or TMP/SMZ monotherapy (monotherapy group). The patients were divided into two subgroups according to the baseline arterial partial pressure of oxygen (PaO 2), patients with arterial PaO 2≥50 mmHg (1 mmHg=0.133 kPa) and PaO 2 <50 mmHg. The clinical efficacies of combination therapy and monotherapy in each subgroup were further compared. Chi-square and Fisher exact test were used for statistical analysis. The three-month survival was estimated by the Kaplan-Meier method, and the three-month survival rates were compared by Log-rank method. Results:A total of 83 patients were enrolled, including 23 in the monotherapy group and 60 in the combination therapy group. There was no significant difference in all-cause hospital mortalities between these two groups (34.8%(8/23) vs 23.3%(14/60), χ2=1.12, P=0.290). Kaplan-Meier survival curves indicated no significant difference in the three-month survival rates between the two groups ( χ2=0.51, P=0.477). There ware no significant differences observed in the positive clinical response rates and the mechanical ventilation rates after seven days of anti-PCP treatment between the two groups ( χ2=0.02 and 0.01, respectively, both P>0.05). In the 52 patients with PaO 2≥50 mmHg, no significant difference in all-cause hospital mortalities was observed between the monotherapy group and the combination therapy group (2/13 vs 25.6%(10/39), χ2=0.14, P=0.704). There was no statistical significance in the three-month survival rates between the two groups ( χ2=0.69, P=0.407). No significant difference was observed either in the clinical positive response rates or the mechanical ventilation rates after seven days of anti-PCP treatment between the two group( χ2=1.02 and 0.69, respectively, both P>0.05). In the 31 patients with PaO 2<50 mmHg, the all-cause hospital mortality in the combination therapy group was 19.0%(4/21), while six of the 10 patients in the monotherapy group died, and the difference was statistically significant (Fisher exact test, P=0.040). The three-month survival rate in the combination therapy group was significantly higher than that in the monotherapy group ( χ2=4.09, P=0.043). There were no significant differences in clinical positive response rate and the mechanical ventilation rate after seven days of anti-PCP treatment between the two group (Fisher exact test, both P>0.05). The overall adverse event rate in the monotherapy group was 87.0%(20/23), with an incidence of 56.5%(13/23) for both electrolyte disturbances and bone marrow suppression. The above incidences in the combination therapy group were 78.3%(47/60), 35.0%(21/60) and 53.3%(32/60), respectively, and all differences were not statistically significant ( χ2=0.34, 3.18 and 0.07, respectively, all P>0.05). Conclusions:The efficacy of combination therapy with TMP/SMZ and caspofungin is comparable to that of TMP/SMZ monotherapy in AIDS patients with moderate to severe PCP requiring mechanical ventilation. However, in AIDS patients with PCP requiring mechanical ventilation with the baseline PaO 2<50 mmHg, the efficacy of combination therapy is statistically superior to that of TMP/SMZ monotherapy. Combination therapy does not increase the risk of adverse events.

Matrix protein p17 is a structural protein of human immunodeficiency virus（HIV）. It not only plays a key role in multiple stages of HIV life cycle，but also is closely associated with HIV-related lymphoma，neurocognitive impairment and breast cancer. This article reviews the role of matrix protein p17 in HIV infection and HIV-related diseases.

Background::A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations.Methods::A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis.Results::The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China.Conclusions::Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally; however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.

Background::The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.Methods::This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.Results::A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs. 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3 % (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs. 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6. Conclusions::Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.Trial Registration::ChiCTR.org.cn, ChiCTR1900021195.

Objective:To investigate the influence of hepatitis B virus (HBV) combined with human immunodeficiency virus (HIV) infection on the efficacy of anti-retroviral therapy (ART).Methods:The data of 269 HIV-infected patients treated in Chongqing Public Health Medical Center from September 2016 to October 2019 were collected. The patients were divided into HIV monoinfection group and HIV/HBV coinfection group. The changes in liver function, CD4 + T lymphocyte count, and HIV RNA level between the two groups were compared when ART started and at different time points (2, 4, 8, 12, 24, 36, 48, and 96 weeks) after ART started. Statistical analysis were performed by independent sample t test, rank sum test and chi-square test. Results:A total of 145 patients with HIV monoinfection and 124 patients with HIV/HBV coinfection were collected. There were no statistically significant differences in liver function indexes (aspartate aminotransferase ( t=9.566), alanine aminotransferase ( t=-4.652) and total bilirubin ( t=-25.476)) between the two groups of patients when ART started (all P>0.05). At 24, 48 and 96 weeks after ART, the CD4 + T lymphocyte counts in the HIV monoinfection group and the HIV/HBV coinfection group were (305.9±156.9)/μL vs (266.2±172.5)/μL, (388.5±226.1)/μL vs (380.8±287.4)/μL and (369.5±191.4)/μL vs (453.6±179.6)/μL, respectively. At 48, 72 and 96 weeks after ART, the CD4 + T lymphocyte count increasing values were 121.0(-52.5, 144.5)/μL vs 156.0(-35.8, 185.8)/μL, 139.0(-116.0, 176.8)/μL vs 114.5(-59.5, 229.0)/μL and -91.0(-110.0, 153.3)/μL vs -94.0(-130.8, 114.3)/μL, respectively. The differences were all not statistically significant ( t=-0.516, -0.066 and -1.414, Z=-1.715、-0.802 and -1.602, respectively, all P>0.05). At 24, 48, and 96 weeks after ART, the HIV RNA inhibition rates in the HIV monoinfection group were 89.7%(130/145), 96.6%(140/145), and 96.6%(140/145), respectively, and those in the HIV/HBV coinfection group were 87.1%(108/124), 92.7%(115/124) and 94.4%(117/124), respectively. The differences were all not statistically significant ( χ2=0.026, 0.053 and 0.017, respectively, all P>0.05). In the second and fourth weeks after ART, the abnormal liver function rates of the HIV monoinfection group were 3.4%(5/145) and 6.2%(9/145), respectively, which were lower than those in the HIV/HBV coinfection group (21.0%(26/124) and 13.7%(17/124), respectively). The differences were both statistically significant ( χ2=20.121 and 4.309, respectively, both P<0.05). However, the abnormal liver function rates in the two group in the 8th week after ART were 10.3%(15/145) and 9.7%(12/124), respectively, and those in the 12th week were 9.0%(13/145) and 9.7%(12/124), respectively, and those in the 24th week were 9.7%(14/145) and 8.9%(11/124), respectively, and those in the 36th week were 9.7%(14/145) and 10.5%(13/124), respectively, and those in the 48th week were 8.3%(12/145) and 8.1%(10/124), respectively, and those in the 96th week were 2.8%(4/145) and 0(0/124), respectively. The differences were all not statistically significant ( χ2=0.330, 0.040, 0.049, 0.051, 0.004 and 3.472, respectively, all P>0.05). Conclusion:HBV coinfection has no adverse effect on the ART effect of HIV-infected patients.

Objective:To understand the current status of HIV self-testing reagent use in pre-exposure prophylaxis (PrEP) and related factors in men who have sex with men (MSM).Methods:From December 2018 to December 2019, "Gold data" online platform (www.jinshuju.com) was used to conduct multicenter PrEP studies in Shenyang, Beijing, Chongqing and Shenzhen of China.Results:A total of 1 222 MSM PrEP users were included in the multicenter study. The average age of the participants was (31.5±8.7) years, and the number of sexual partners in the past three months was 3 ( P 25, P 75:2,6). The proportions of those who did not use condoms in anal sex with fixed, casual and commercial partners were 62.7% (456/727), 56.3% (440/781) and 41.0% (16/39), respectively. Up to 74.5% (910/1 222) of participants had used HIV self-testing reagents, and the number of HIV self-testing during last year was 3 ( P 25, P 75:2,5). The multivariate logistic regression analysis indicated that compared with age group >40 years, those with education level of junior high school or below, those with psychological identity as female, event driven PrEP users, those never using new type drugs in past 3 months, the participants aged 18- years (a OR=2.06, 95% CI: 1.35-3.14), 26- years (a OR=2.72, 95% CI: 1.77-4.17), 31- years (a OR=1.76, 95% CI: 1.19-2.59), undergraduates (a OR=2.18, 95% CI: 1.35-3.49), graduate students and above (a OR=3.06, 95% CI: 1.69-5.54), those with psychological identity as male (a OR=3.22, 95% CI: 1.55-6.70), daily PrEP users (a OR=1.35, 95% CI: 1.03-1.78), and new type drug users in the past three months (a OR=1.72, 95% CI: 1.30-2.28) had higher proportions of HIV self-testing behaviors. Conclusions:The proportion of HIV self-testing in MSM PrEP users was high, while it was relatively low in older age group, event driven PrEP users and MSM never using new type drugs. To assess and improve the effectiveness and compliance of PrEPs, it is necessary to provide better HIV self-testing service for MSM with low HIV self-testing rate.

Objective:To investigate the drug-resistant mutations of human immunodeficiency virus-1 (HIV-1) in patients who received highly active antiretroviral therapy (HAART) from 2014 to 2018.Methods:A total of 880 patients with HIV-1 infection who had been treated with HAART for more than six months in Chongqing Infectious Disease Medical Center from May 2014 to December 2018 were enrolled. Plasma samples were collected, and one-step reverse transcription-polymerase chain reaction (PCR) and nested PCR were taken to amplify protease and reverse transcriptase regions of HIV-1 pol gene region. The obtained amplified nucleotide sequences were compared with the drug resistance database for antiviral drug resistance analysis. Viral genotyping tool software was used to analyze HIV-1 subtype distribution. The categorical variables were compared using chi-square test. Results:Among 880 patients, the plasma HIV-1 viral load was (4.12±0.63) lg copies/mL, the CD4 + T lymphocyte count was (251±124)/μL, and the median duration of antiviral therapy was 26 months. In the subtypes analysis, the circulating recombinant form (CRF) 01-AE subtype was the largest proportion of HIV-1 subtypes, accounting for 38.9%(342/880), and the CRF07-BC subtype accounted for 28.5%(251/880), B+ C subtypes accounted for 16.2%(143/880). Drug-resistant mutations were detected in 534 patients, with a total drug resistance rate of 60.7%. The drug resistance rates of nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) were 51.0%(449/880), 58.6%(516/880) and 1.7%(15/880), respectively. The drug resistances to lamivudine, emtricitabine, efavirenz, and nevirapine were serious, and the medium/high resistance rates were 46.8%(412/880), 46.8%(412/880), 51.3%(451/880), and 53.6%(472/880), respectively, while those to zidomidudine (6.0%, 53/880), etravirin (9.0%, 451/880) and PI were not serious. M184IV (47.3%), K65R (22.2%) and K70RE (12.6%) were the most frequent mutations for NRTI. K103NS (25.1%), V106A (19.7%) and V179DE (14.4%) were the most frequent mutations for NNRTI. The most common drug-resistant mutations for PI were L10FIV (7.4%) and A71IVT (6.5%). The drug resistance rate of CRF01-AE subtype (69.3%, 237/342) was higher than those of CRF07-BC subtype (49.8%, 125/251) and B+ C subtype (51.0%, 73/143), the differences were statistically significant ( χ2=22.6 and 14.6, respectively, both P<0.05). Conclusions:The incidence of drug resistance is high among HIV-1 infected patients after six-month HAART treatment in Chongqing City. The drug resistance to NNRTI is the most common, followed by NRTI, while PI is less resistant. Drug resistance is the main reason for the virological breakthrough in HIV-1 infected patients.

Cases of 2019-nCoV nucleic acid and antibody (IgM and IgG total antibody) after discharge from a hospital in Chongqing were continuously monitored. It was found that 5 cases of "re-positive" phenomenon, 5 cases of antibody were positive, and there was a trend of increasing with time. "Re-Positive" may be related to the following three factors. Children with asymptomatic infection had a long time of fecal detoxification.There were two consecutive nucleic acid tests "false negative" caused by various reasons.The virus clearance in patients was not complete, and the discharge standard was not conservative enough. The analysis of the causes of "Re-Positive" patients and the discussion of its infection will help us reveal more characteristics of this virus, and to provide a new basis for the discharge standard in the constantly updated diagnosis and treatment programme.

Objective To investigate the short- to medium-term therapeutic effects of a new internal fixation device,intraosseous internal fixation(IO-FIX),in the foot-ankle arthrodesis.Methods From August 2016 to December 2018,32 patients(40 feet) underwent foot-ankle arthrodesis with IO-FIX at Department of Orthopaedic Surgery,The Ninth Peopled Hospital of Shanghai.They were 6 males and 26 females,aged from 23 to 83 years(61.7±15.1 years).There were 28 cases(36 feet) of hallux valgus,2 cases(2 feet) of ankle arthritis,one case(1 foot) of ankle rheumatoid arthritis and one case(1 foot) of naviculocuneiform arthrosis.The therapeutic effects were assessed in terms of imaging evaluation,American Orthopaedic Foot and Ankle Society(AOFAS) score,fusion rate and full weight-bearing time.Results The follow-up ranged from 3.0 to 31.3 months(mean,12.6 months).The total fusion rate was 95.0%(38/40);the total AOFAS score increased significantly from preoperative 41.9±9.5 to postoperative 86.9±4.7(P<0.05).The 28 patients(36 feet) with hallux valgus achieved a successful fusion rate of 97.2%(35/36) and full weight-bearing at 8 weeks after operation.Their fusion time ranged from 45 to 64 days(57.1 days).Their metatarsophalangeal angle was decreased significantly from 52.10±13.50 preoperatively to 13.40±4.90 postoperatively and their 1-2 intermetatarsal angle significantly from 14.5°±2.4°to 8.90±2.4°(P<0.05).Their AOFAS ankle-hindfoot score was improved significantly from 41.8±9.9 to 87.0±4.8(P<0.05).All the 3 cases of ankle arthrodesis achieved good bone union and full weight-bearing within 12 weeks and their AOFAS ankle-hindfoot score was improved significantly from preoperative 43.4±3.5 to 86.3±3.5 at the final follow-up.Conclusion In foot-ankle joint arthrodesis,due to advantages of stable fixation,zero profile,limited soft tissue irritation,reinforced bone bridge and easy reproducibility,10-FIX can lead to satisfactory short- to mid-term therapeutic effects.