Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study.

Background: The number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018. Methods: Cohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation. Results: HIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63-1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57-3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09-0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03-0.29); but higher among children with late ART initiation at 1-3 months (AHR 2.30, 95% CI 1.07-4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04-4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41-0.95), but higher among children with late ART initiation at 1-3 months (AHR 1.55, 95% CI 1.05-2.30). Conclusion: Supportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

Decreasing HIV, Syphilis, and Hepatitis C Infection After a Decade of Harm Reduction Implementation Among Drug Users in Southwestern Areas of China.

OBJECTIVE: Since 2003, the Chinese central government has implemented several harm reduction and preventive measures to control HIV. We aim to describe epidemiological trends of HIV, hepatitis C virus (HCV), and syphilis in Guangxi drug users after the policy implementation. METHOD: A total of 12,161-15,870 drug users in Guangxi, China, were recruited annually from 2009 to 2015 through community outreach or snowball sampling. The participants' demographics, behavior, and infection status were used to characterize rates of protective behaviors and disease prevalence (HIV, syphilis, and HCV). Chi-squared trend testing was used. RESULTS: Relative to baseline, the prevalence of HIV, HCV, and syphilis decreased from 13.6% to 6.2%, 68.0% to 50.5%, and 8.5% to 5.2%, respectively, by 2015. Concurrently, the rate of injecting drugs, needle sharing, unprotected last sexual encounter, and regular unprotected intercourse decreased from 82.6% to 64.5%, 24.1% to 5.5%, 66.6% to 39.7%, and 74.0% to 51.2%, respectively. The usage of prevention services, methadone maintenance therapy or needle exchange, peer education programs, HIV testing in the previous year, and knowledge of HIV status increased from 63.4% to 93.6%, 52.0% to 56.6%, 37.4% to 43.1%, 45.3% to 91.3%, and 76.7% to 99.4%, respectively, from 2009 to 2015. CONCLUSIONS: After a decade of HIV control policies, this was the first Chinese study to show a decreasing prevalence of HIV, HCV, and syphilis in the context of increasing uptake of protective services and behaviors.

Declining Inconsistent Condom Use but Increasing HIV and Syphilis Prevalence Among Older Male Clients of Female Sex Workers: Analysis From Sentinel Surveillance Sites (2010-2015), Guangxi, China.

Clients of female sex workers (CFSWs) are a bridge population for the spread of HIV and syphilis to low or average risk heterosexuals. Most studies have examined the point prevalence of these infections in CFSWs. Limited evidence suggests that older age CFSWs are at a higher risk of acquiring sexually transmitted diseases compared with younger clients. Thus, we sought to describe long-term trends in HIV, syphilis, and hepatitis C (HCV) to better understand how these infections differ by sex worker classification and client age. We also examined trends in HIV, syphilis, and HCV among categories of female sex workers (FSWs).We conducted serial cross-sectional studies from 2010 to 2015 in Guangxi autonomous region, China. We collected demographic and behavior variables. FSWs and their clients were tested for HIV, syphilis, and HCV antibodies. Positive HIV and syphilis serologies were confirmed by Western blot and rapid plasma regain, respectively. Clients were categorized as middle age (40-49 years) and older clients (≥50 years). FSWs were categorized as high-tier, middle-tier, or low-tier based on the payment amount charged for sex and their work venue. Chi-square test for trends was used for testing changes in prevalence over time.By 2015, low-tier FSWs (LTFSWs) accounted for almost half of all FSWs; and they had the highest HIV prevalence at 1.4%. HIV prevalence declined significantly for FSWs (high-tier FSW, P = 0.003; middle-tier FSWs; P = 0.021; LTFSWs, P < 0.001). Syphilis infections significantly declined for FSWs (P < 0.001) but only to 7.3% for LTFSWs. HCV and intravenous drug use were uncommon in FSWs. HIV prevalence increased for older age clients (1.3%-2.0%, P = 0.159) while syphilis prevalence remained stable. HCV infections were halved among older clients in 3 years (1.7%-0.8%, P < 0.001). Condom use during the last sexual encounter increased for FSWs and CFSWs. Few clients reported sex with men or intravenous drug use. Clients preferred LTFSWs, especially older clients (81.9%).Our results suggest that HIV and syphilis infections are increasing in older clients who prefer LTFSWs. HIV and syphilis are likely increasing in Guangxi Province through heterosexual transmission.

Near Full-Length Genomic Characterization of a Novel HIV Type 1 CRF01_AE/CRF07_BC Recombinant Form Transmitted Between a Heterosexual Couple in Guangxi, China.

In this research, we reported a new second generation recombinant form (GXDY460B) between circulating recombinant form (CRF)01_AE and CRF07_BC in a seroconversion couple who obtained the virus from her husband by heterosexual behavior. The analysis result of the near full-length genomic characterization showed that the genome comprises at least 12 interlaced segments, including six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. Cocirculation of multiple virus subtypes and multiple infection routes have existed for a long time in Guangxi, but the recombinant strain was rarely reported among heterosexual transmission population because of its lower crowd confounding degree than men who have sex with men and injecting drug user population. It is the first time that the unique recombinant form (URF) between CRF01_AE and CRF07_BC was identified among heterosexual transmission in Guangxi. The emergence of the novel recombinant helps to understand the pattern of the URF virus.

Low Virologic Failure and Drug Resistance among HIV-Infected Patients Receiving Hospital-Based ART While Care and Outreach through Community in Guangxi, China.

OBJECTIVES: To investigate human immunodeficiency virus (HIV) virologic suppression and drug resistance among HIV-infected patients receiving first-line antiretroviral treatment (ART) in hospitals while community care and outreach through local health workers in Guangxi, China. DESIGN: This was a series of cross-sectional surveys from 2004 to 2012 in Guangxi, supported by the Chinese National HIVDR Surveillance and Monitoring Network Working Group. SETTINGS: Guangxi, China. METHODS: Demographic, ART, and laboratory data (CD4(+) cell count, viral load, and drug resistance) were analyzed. Factors associated with virologic suppression were identified by logistic regression analysis. RESULTS: A total of 780 patients were included in this study. The median treatment duration was 20.6 months (IQR 6.6-35.9). Of 780 study participants, 95.4% of patients (744/780) had HIV virologic suppression. Among these, of the 143 patients who were infected through drug injection, only 10 (7.0%) experienced virologic failure, and the overall prevalence of HIV drug resistance was 2.8% (22/789). Factors associated with virologic suppression in the final multivariate models included self-reported missing doses in the past month (compared to not missing doses in the past month, AOR = 0.2, 95% CI: 0.1-0.6) and initial ART regimen without 3TC (compared to initial ART regimen with 3TC, AOR = 0.2, 95% CI: 0.1-0.4). Moreover, the trend chi-square test showed that the proportion of virologic suppression increased over time from 2004 to 2012 (P = 0.002). CONCLUSION: This study first demonstrated that HIV patients infected through various transmission routes can achieve an excellent treatment outcome in hospitals at or above the county level for free first-line ART in Guangxi. It is an important of ART education and adherence to intervention for achieving better treatment outcomes.

Short Communication: Low False Recent Rate of Limiting-Antigen Avidity Assay Among Long-Term Infected Subjects from Guangxi, China.

Assays used for HIV cross-sectional incidence testing can misclassify some individuals with nonrecent HIV infection as recently infected, overestimating HIV incidence. We analyzed the frequency and factors associated with false-recent misclassification on subjects from Quangxi, China known to have long-term infection using the limited antigen-avidity assay (LAg-Avidity). Stored samples from treatment-naive individuals from Guangxi, China were tested using the LAg-Avidity. A total of 362 samples from individuals known to be infected 2 to 13.5 years were tested and the false-recent rate (FRR), the frequency of samples with a positive result, was determined at different cutoff values of the assay. Additionally, factors associated with misclassification were determined. The FRR of the LAg-Avidity was 1.1% (4/362) using a cutoff of 1.5 normalized optical density units (OD-n). All four samples had viral loads >1,000 copies/ml. Using a cutoff of 3.0 OD-n the FRR was 5.5% (20/362), with four samples having viral loads <1,000 copies/ml. Factors associated with a higher odds of misclassification were female gender (OR 7.7, 95% CI 1.0-56.4) and being a female sex worker (OR 31.3, 95% CI 4.0-242). At the higher cutoff, being of Zhuang decent, relative to Han, had higher odds of misclassification (OR 6.2, 95% CI 1.99-19.0). The LAg-Avidity assay had a low FRR in this Chinese population. Further investigations of the higher frequency of low LAg-Avidity results seen in female sex workers and individuals of Zhuang descent should be explored in a larger study.

Genetic Characteristics of CRF01_AE Among Newly Diagnosed HIV-1-Infected 16- to 25-Year Olds in 3 Geographic Regions of Guangxi, China.

The aim of this study was to analyze the distribution of clusters and drug resistance of CRF01_AE among newly diagnosed, treatment-naïve HIV-infected teenagers and young adults in 3 major HIV-affected geographic regions of Guangxi Province, including the cities of Hezhou, Liuzhou, and Nanning. Samples were sequentially collected from newly diagnosed HIV-infected 16- to 25-year olds in these 3 regions from 2009 to 2013. The viral genome was extracted, and the partial pol gene was amplified and sequenced. Phylogenetic analyses were used to determine HIV-1 subtypes and CRF01_AE clusters. Transmitted drug resistance (TDR) mutations were identified using the 2009 WHO list of TDR mutations. A total of 216 sequences were obtained from CRF01_AE strains, which accounted for 83.1% of the 260 genotyped samples, of which 36 were from Hezhou, 147 from Liuzhou, and 33 in Nanning. Most (83.3%, 180/216) were from heterosexuals, followed by injection drug users (5.6%), homosexuals (4.2%), and unknown risk group (6.9%). Based on phylogenetic analyses by the maximum likelihood method, 5 distinct clusters (cluster 1-5) were identified with 213 (98.6%) sequences, whereas 3 (1.4%) sequences were ungrouped. In Hezhou, 88.9% (32/36) of CRF01_AE infections were caused by cluster 2, and 11.1% (4/36) were caused by cluster 1. In Liuzhou, 83.0% (122/147) of the CRF01_AE strains were found in cluster 1, 11.6% (17/147) from cluster 2, 1.4% (2/147) from cluster 3, 2.7% (4/147) from cluster 4, and 0.7% (1/147) from cluster 5. The distribution of CRF01_AE clusters was more even in Nanning than it was in the other 2 regions, with 18.2% (6/33) from cluster 1, 36.3% (12/33) from cluster 2, 9.1% (3/33) from cluster 3, 18.2% (6/33) from cluster 4, and 12.1% (4/33) from cluster 5. The most frequent TDR mutations were M46I (2) in the protease region and Y181C (2) from the reverse transcriptase fragment. Clusters 1 and 2 of CRF01_AE strains were prevalent in Liuzhou and Hezhou, respectively. However, multiple CRF01_AE clusters existed in Nanning. This can be partially explained by the high mobility of laborers in Nanning, the capital city of Guangxi. The prevalence of TDR was low.

Prevalence of transmitted HIV-1 drug resistance remains low in Guangxi, China, eight years after scale-up of highly-active antiretroviral therapy.

OBJECTIVES: Highly-active antiretroviral therapy (HAART) was scaled up in Guangxi, China in 2005. The number of individuals receiving free HAART increased dramatically from June 2010 under the Guangxi Government's anti-HIV programme. We aimed to determine the prevalence of HIV-transmitted drug resistance (TDR) of Guangxi. METHODS: HIV-positive, antiretroviral-naive individuals were recruited from the east (Hezhou), south (Qinzhou), west (Baise), north (Guilin) and centre (Laibin) of Guangxi. The pol gene of the virus from the individuals was analysed. RESULTS: The overall prevalence of HIV TDR was 3.2% (7/216, 95% CI 0.9-5.5). The prevalence rates in Baise, Guilin, Hezhou, Qinzhou and Laibin are 4.9% (2/41, 95% CI -1.7 to 11.5), 2.3% (1/44, 95% CI -2.1 to 5.7), 4.7% (2/43, 95% CI -1.6 to 11.0), 2.6% (1/38, 95% CI -2.5 to 7.7) and 2.0% (1/50, 95% CI -1.9 to 5.9), respectively. No significant difference in the prevalence was found among them. No factors were found to be associated with TDR, including CD4 cell counts, viral loads and genotypes. The subtypes CRF01_AE, CRF07_BC, CRF08_BC and B were found. Subtype CRF08_BC is the predominant subtype in Baise while CRF01_AE is the predominant subtype elsewhere in Guangxi. CONCLUSIONS: The prevalence of TDR in antiretroviral-naive patients in Guangxi remains low 8 years after scale-up of HAART.

Genotypic and phenotypic characterization of HIV-1 CRF01_AE env molecular clones from infections in China.

BACKGROUND: Although a great number of HIV-1 pseudoviruses have been generated for neutralization assays, circulating recombinant forms, such as CRF01_AE, are not included. Given the increasing prevalence of CRF01_AE, the establishment of a pool of CRF01_AE env isolates for the evaluation of potential HIV vaccines is needed. MATERIALS AND METHODS: Full-length env genes were cloned from HIV-1 CRF01_AE-infected plasma samples collected in China and used to establish Env-pseudotyped viruses. The neutralization phenotypes of the pseudoviruses were characterized by testing against broadly neutralizing monoclonal antibodies, coreceptor antagonists, and 42 plasma samples that include 3 main prevalent HIV-1 subtypes in China. RESULTS: Thirty-four genetically distinct CRF01_AE env genes were cloned and used to generate pseudotyped viruses. Of the 34 pseudoviruses, 32 used CCR5 as a coreceptor and 2 used CXCR4. The majority of pseudoviruses were resistant to the neutralizing antibodies IgG1b12 and 2G12 and susceptible to 2F5 and 4E10. There was significant variation of the neutralization susceptibility of pseudoviruses against 42 HIV-1-positive plasma samples. Based on their overall neutralization susceptibilities, the 34 CRF01_AE pseudoviruses were classified into 3 tiers: high, medium, and low. CONCLUSION: The CRF01_AE pseudovirus isolates should be included in the panel of pseudoviruses used to assess vaccine-elicited neutralizing antibodies.

[The changes and significance of T lymphocytes and subsets before and after receiving highly active anti-retroviral therapy in children infected with HIV or AIDS patients].

OBJECTIVE: To investigate the changes of the T lymphocytes and their subsets before and after receiving highly active anti-retroviral therapy (HAART) in children who were infected with HIV or AIDS patients. METHODS: Ninety-nine children met the criteria were recruited. All of them had received HAART in Guangxi Center for Disease Control and Prevention from May 2006 to April 2009. Peripheral blood of 2 milliliter was collected before treatment (D0) and after 3, 6, 12, 18, 24, 30, and 36 months (M3, M6, M12, M18, M24, M30 and M36), respectively. Four-color fluorescence flow cytometry was used for the detection of the absolute numbers of CD3(+), CD4(+), CD8(+) T lymphocytes in peripheral blood. And then, the percentages of CD3(+), CD4(+), CD8(+) T lymphocytes in the CD45(+) cells and the ratio of CD4/CD8 were calculated. RESULTS: Sixteen-five (65.66%) cases were treated with lamivudine (3TC)/zidovudine (AZT)/nevirapine (NVP), and 16 (16.16%), 8 (8.08%) and 10 (10.10%) cases were treated with 3TC/stavudine (D4T)/NVP, 3TC/AZT/efavirenz (EFV) and 3TC/AZT/lpv-rtv (LPV/r), respectively. The median of the ratio of CD4/CD8 were 0.39, 0.51, 0.61, 0.65, 0.70, 0.73 and 0.76 in M3, M6, M12, M18, M24, M30 and M36, respectively which were significantly higher than that in D0 (0.19) (Z values were -5.158, -7.375, -9.078, -8.853, -8.373, -5.845 and -5.844 respectively, P < 0.000). The median of CD4% were 16.92%, 22.70%, 25.54%, 26.66%, 27.99%, 30.36% and 29.30% respectively in M3, M6, M12, M18, M24, M30 and M36 respectively, which were also higher significantly than that in D0 (9.92%) (Z values were -5.268, -7.568, -9.496, -9.171, -8.760, -6.190 and -5.964 respectively, P < 0.000). In addition, the median of the absolute numbers of CD4(+)T lymphocytes in peripheral blood were 631, 813, 1050, 946, 1057, 1166 and 894 cells/mm(3) respectively in M3, M6, M12, M18, M24, M30 and M36, which were higher significantly than that of D0 (382 cells/mm(3)) (Z values were -3.318, -5.288, -6.661, -5.886, -5.801, -4.110 and -3.600 respectively, P < 0.000). However, the median of CD8% were 47.25%, 43.01%, 43.04%, 42.60%, 41.37%, 40.83% and 38.31% respectively in M3, M6, M12, M18, M24, M30 and M36, which were lower significantly than that of D0 (53.17%) (Z values were -3.082, -4.697, -5.282, -5.846, -5.757, -3.883 and -4.380 respectively, P < 0.001). CONCLUSION: There is certain rules for the changes of T lymphocytes and their subsets, which may play important roles in the evaluation of the therapeutic effect and the clinical application guidance of HAART.

Maintaining low HIV type 1 env genetic diversity among injection drug users infected with a B/C recombinant and CRF01_AE HIV type 1 in southern China.

HIV-1 outbreaks in Guangxi Province, southern China were initiated from two separate border cities in 1996 and 1997. Drug users in Pingxiang City, which borders Vietnam, were infected with CRF01_AE HIV-1, and drug users in Baise City, which borders Yunan Province, were infected with a novel B/C recombinant HIV-1. Since 1997, HIV-1 has been rapidly spreading in Guangxi, including its capital city Nanning. Survey data indicated that HIV-1 prevalence among IDUs in new outbreak regions increased 8 to 42% within 1 year. The B/C recombinants obtained from five separate regions in Guangxi, which span a 4-year time frame, were remarkable for their low intersubject env V3 diversity, less than 0.2%. Similarly, the CRF01_AE from IDUs over a 3-year time frame had low intersubject env V3 diversity of less than 1.6%. Different patterns of sequence variations in the V3 and V4 regions were observed for the B/C recombinant and the CRF01_AE HIV1. The rapid spreading of homogeneous HIV-1 strains in Guangxi may have important implications for HIV transmission as well as vaccine development and evaluation.