1.HIV Pretreatment Drug Resistance and Transmission Clusters among Newly Diagnosed Patients in the China-Myanmar Border Region, 2020-2023.
Huan LIU ; Yue Cheng YANG ; Xing DUAN ; Yi Chen JIN ; Yan Fen CAO ; Yi FENG ; Chang CAI ; He He ZHAO ; Hou Lin TANG
Biomedical and Environmental Sciences 2025;38(7):840-847
OBJECTIVE:
This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China.
METHODS:
Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site.
RESULTS:
Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL.
CONCLUSION
The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans
;
HIV Infections/virology*
;
China/epidemiology*
;
Drug Resistance, Viral
;
Male
;
Adult
;
Female
;
Middle Aged
;
HIV-1/genetics*
;
Anti-HIV Agents/therapeutic use*
;
Myanmar/epidemiology*
;
Young Adult
;
Prevalence
;
Adolescent
;
Mutation
2.Calculating the Number of Pregnant Women Receiving Standardized Services for PMTCT of HIV in Liangshan Prefecture, Based on the Equivalent Method.
Shui Ling QU ; Ai Ling WANG ; Xiao Ping PAN ; Xiao Yan WANG ; Hui Ming LUO ; Tong ZHANG
Biomedical and Environmental Sciences 2020;33(10):745-749
Objective:
To calculate the number of pregnant women who receive standardized prevention of mother-to-child transmission (PMTCT) services for HIV annually.
Methods:
HIV-positive pregnant women in six counties of Liangshan Prefecture in 2017 were selected as study subjects. The entire process, from when the subjects first received the PMTCT of HIV services to the end, was divided into four stages, which were further divided into 25 phases. The equivalent coefficient was used to indicate the weight of workload in each phase. Seven experts were invited to score the equivalent coefficient; the number of pregnant women who received standardized services to prevent the transmission of HIV was calculated.
Results:
A total of 663 HIV-positive pregnant women were registered in six Liangshan Prefecture counties in 2017. This figure was converted into 7,780 person-months devoted to HIV-positive pregnant women, with 260 person-months (3.34%) spent on the first antenatal care, 1,510 person-months (19.41%) during pregnancy, 378 person-months (4.86%) on delivery, and 5,632 person-months (72.39%) on post-partum period. The equivalent coefficient calculation showed that 314 HIV-positive pregnant women received standardized PMTCT services.
Conclusion
The number of pregnant women receiving standardized services for the PMTCT of HIV can be calculated accurately using the equivalent method to identify the gap between the level of PMTCT of HIV intervention services needed and the actual workload.
Anti-HIV Agents/therapeutic use*
;
Female
;
HIV Infections/virology*
;
Humans
;
Infectious Disease Transmission, Vertical/prevention & control*
;
Pregnancy
;
Pregnant Women
3.Transmission cluster and network of HIV-1 CRF01_AE strain in China, 1996-2014.
X L WANG ; L JIA ; H P LI ; Y J LIU ; J W HAN ; T Y LI ; J Y LI ; L LI
Chinese Journal of Epidemiology 2019;40(1):84-88
Objective: To understand the transmission patterns and risk factors of HIV-1 strain CRF01_AE subtypes in China, and to provide guidance for the implementation of precise intervention. Methods: A total of 2 094 CRF01_AE pol sequences were collected in 19 provinces in China between 1996 and 2014. Phylogenetic tree was constructed by PhyML 3.0 software to select the transmission clusters. Transmission network was constructed by Cytoscape 3.6.0, which was further used for exploring of the major risk factors. Results: Of the 2 094 sequences, 12.18% (255/2 094) were in clusters. A total of 82 transmission clusters were identified. The numbers of clusters and contained sequences in intra-provincial transmission (61, 173) were significantly more than those in inter-provincial transmission (21, 82). The ratio of transmission clustering in MSM increased over time from 2.41% (2/83) during 1996-2008 to 23.61% (72/305) during 2013-2014, showing a significant upward trend (χ(2)=27.800, df=1, P=0.000). The proportion of MSM with inter-provincial transmission clusters were higher than those with intra-provincial transmission clusters, which increased from 0.67% (2/297) during 1996-2008 to 6.36%(30/472) during 2013-2014, showing a significant upward trend (χ(2)=20.276, df=1, P=0.000). The transmission rate in homosexuals of the inter-transmission clusters (86.59%, 71/82) was higher than that of intra-provincial transmission clusters (56.65%, 98/173), and the difference was statistically significant (χ(2)=22.792, P=0.000). The proportion of inter-provincial transmission clusters with more than 2 transmission routes (33.33%, 7/21) was higher than that of intra-provincial clusters (13.11%, 8/61), and the difference was statistically significant (χ(2)=4.273, P=0.039). Results from the transmission network analysis indicated that the proportion of high risk population (degree≥4) with inter-provincial transmission clusters (51.22%, 42/82) was significantly higher than that with intra-provincial transmission clusters (26.59%, 46/173), and the difference was statistically significant (χ(2)=14.932, P=0.000). Inter-provincial clusters were mainly detected in and and MSM. Conclusions: Complex transmission networks were found for HIV-1 CRF01_AE strains in the mainland of China. Inter-provincial transmission clusters increased rapidly, MSM played an important role in the wide spread of the strain. More researches in transmission networks are needed to guide the precision intervention.
China/epidemiology*
;
HIV Infections/virology*
;
HIV-1/isolation & purification*
;
Homosexuality, Male/statistics & numerical data*
;
Humans
;
Male
;
Phylogeny
4.Human leukocyte antigen polymorphism of HIV infected persons without disease progress for long-term in Henan province, 2011-2016.
X J XUE ; J Z YAN ; D CHENG ; C H LIU ; J LIU ; Z LIU ; S A TIAN ; D Y SUN ; B W ZHANG ; Z WANG
Chinese Journal of Epidemiology 2019;40(1):89-92
Objective: To understand the disease progression and human leukocyte antigen (HLA) gene polymorphism of HIV-infected persons without disease progress for long term, also known as long-term non-progressors (LTNPs), in Henan province. Methods: A retrospective study was conducted in 48 LTNPs with complete detection and follow-up information during 2011-2016 in Henan. Changes of CD(4)(+)T cells counts (CD(4)) and viral load (VL) during follow-up period were discussed. Polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) was used for the analyses of HLA-A, HLA-B and HLA-DRB1 alleles between LTNPs and healthy controls. Results: From 2011 to 2016, forty-eight LTNPs showed a decrease of the quartile (P(25)-P(75)) of CD(4) from 601.00 (488.50-708.72)/μl to 494.00 (367.00-672.00)/μl, and the difference was significant (P<0.05). The increase of the quartile (P(25)-P(75)) of log(10)VL from 3.40 (2.87-3.97) to 3.48 (2.60-4.37), but the difference was not significant (P>0.05). HLA polymorphism analysis revealed that HLA-B*13:02 and HLA-B*40:06 were more common in LTNPs (P<0.05), while HLA-B*46:01 and HLA-DRB1*09:01 were more common in healthy controls (P<0.05). Conclusions: The CD(4) of LTNPs in Henan showed a downward trend year by year. HLA-B*13:02 and B*40:06 might be associated with delayed disease progression for HIV infected persons in Henan.
Adult
;
Alleles
;
Asian People/genetics*
;
China
;
Disease Progression
;
Female
;
HIV
;
HIV Infections/virology*
;
HIV-1/immunology*
;
HLA-B Antigens/genetics*
;
Humans
;
Middle Aged
;
Polymorphism, Genetic
;
Retrospective Studies
;
Viral Load
5.Molecular transmission clusters on HCV genotypes among newly reported HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture of Yunnan province, 2016.
Y K WANG ; X C CHEN ; J B WANG ; X DUAN ; S J ZHOU ; J YANG ; T YANG ; R H YE ; Y C YANG ; S T YAO ; S DUAN ; N HE
Chinese Journal of Epidemiology 2019;40(2):191-195
Objective: To understand the characteristics on major strain subtypes of hepatitis C virus among HIV/HCV co-infected patients, so as to explore the molecular transmission clusters and related risk factors of HCV strains. Methods: A total of 336 newly reported HIV-infected patients were diagnosed as HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture (Dehong) in 2016. We used Nested PCR to amplify CE1 and NS5B genes among 318 samples with plasma levels above 200 μl, before using the combining phylogenetic tree and constructing molecular propagation network method to analyze the related data. Results: A total of 267 HIV/HCV co-infection patients who had met the HCV genotyping requirements were screened the gene subtypes were diversified. Among these genotypes, proportions of 3b, 6n, 6u, 1a, 3a and other subtypes appeared as 32.6% (87/267), 18.4% (49/267), 15.7%(42/267), 13.1%(35/267), 11.2%(30/267) and 9.0%(24/267) respectively. Molecular transmission network of five major HCV genotypes was constructed with a clustering rate of 39.1% (95/243). The clustering rate of subtype 1a was the highest, as 71.4% (25/35). Results from the multivariate logistic regression showed that ethnic minorities other than the Yi and Jingpo (vs. the Han, OR=0.17, 95%CI: 0.04-0.71), the married spouses (vs. the unmarried, OR=0.42, 95%CI: 0.18-0.94), the 6n and 3a subtype (vs. the 3b subtype, OR=0.34, 95%CI: 0.12-0.95; OR=0.22, 95%CI: 0.05-0.93) were more difficult to form transmission clusters. However, the 6u and 1a subtype (vs. the 3b subtype, OR=3.10, 95%CI: 1.21-7.94; OR=4.00, 95%CI: 1.32-12.11) seemed more likely to form the transmission clusters. Conclusion: Ethnicity, marital status and genetic subtypes were factors significantly associated with the formation of transmission clusters related to the major HCV gene subtypes among newly reported HIV/HCV co-infection in Dehong.
AIDS-Related Opportunistic Infections/virology*
;
Asian People
;
China/epidemiology*
;
Coinfection
;
Genotype
;
HIV Infections/virology*
;
Hepacivirus/isolation & purification*
;
Hepatitis C/virology*
;
Humans
;
Phylogeny
;
Polymerase Chain Reaction
6.Characteristic and dynamic of HIV-1 subtype distribution in men who have sex with men in Guangzhou, 2008-2015.
Z G HAN ; Y L ZHANG ; H WU ; W B CHENG ; C Y LIANG ; F ZHONG ; K GAO ; H F XU
Chinese Journal of Epidemiology 2018;39(1):67-71
Objective: To understand the characteristics and dynamic of HIV-1 subtype distribution in men who have sex with men (MSM) in Guangzhou between 2008 and 2015. Methods: HIV-1 RNAs were extracted from serum samples of the individuals newly diagnosed with HIV-1 infection among MSM living in Guangzhou between 2008 and 2015. The pol gene segments of HIV-1 genome from these RNA samples were amplified by nested reverse transcription polymerase chain reaction (nested-PCR) and were sequenced. Subsequently, the phylogenetic tree was reconstructed using pol sequences of samples and references together and the subtype of HIV-1 was determined. The distributions of HIV-1 subtypes detected in MSM with different demographic characteristics in different years were compared. Results: A total of 2 210 pol gene segments were successfully obtained from 2 473 serum samples of the MSM. The average age of 2 210 MSM was 30.19 years with standard deviation of 8.22 years, the unmarried MSM and those in Han ethnic group accounted for 73.39% and 90.81%, respectively. The proportion of subtype CRF07_BC (38.10%) was highest, followed by CRF01_AE (34.84%), CRF55_01B (14.62%), B (6.06%), URFs (3.58%), CRF59_01B (2.17%) and other subtypes (0.63%). The annual proportions of subtype B (P=0.000, 99%CI:0.000-0.000), CRF07_BC (χ(2)=14.965, P=0.036), CRF55_01B (χ(2)=18.161, P=0.011) and URFs (P=0.001, 99% CI: 0.000-0.001) were significantly different. The proportion of subtype B showed a gradual decrease from 14.08% to 4.33% (P=0.000, 99%CI: 0.000-0.000), while the proportion of URFs rapidly increased from 0% to 6.40% (P=0.000, 99% CI: 0.000-0.000). The rate of URFs was significantly higher in farmers and migrant workers than in other groups (P=0.017, 99%CI: 0.014- 0.020) and the rate of URFs was higher in individuals who had multi sexual partners (χ(2)=5.733, P=0.017). Conclusions: CRF07_BC and CRF01_AE were the predominant HIV-1 subtypes and multiple subtypes co-circulated among MSM in Guangzhou between 2008 and 2015. The recombinations of HIV-1 continue to occur in MSM. Strengthening behavioral intervention for farmers, migrant workers and individuals who have multi sexual partners has the important epidemiological significance against the emerging and circulating of the novel recombinant virus among MSM in Guangzhou.
China/epidemiology*
;
Genes, pol
;
Genotype
;
HIV Infections/virology*
;
HIV Seropositivity/genetics*
;
HIV-1/isolation & purification*
;
Homosexuality, Male
;
Humans
;
Male
;
Phylogeny
;
Polymerase Chain Reaction
;
RNA, Viral/blood*
;
Sexual Behavior
7.Application of Bernoulli Process Model fitting the effect of intervention measures on sexual transmission among HIV sero-discordant couples.
Chinese Journal of Epidemiology 2018;39(6):755-759
Objectives: To undersand the outcomes of major intervention measures on sexual transmission among HIV sero-discordant couples. Methods: Bernoulli Process Model was applied to model the major influencing factors of HIV transmission among HIV sero-discordant couples. The major influencing factors appeared as consistent condom use, antiretroviral therapy, frequency of sexual behavior. These parameters were from the HIV sero-discordant couples in 30 counties in 4 provinces (Guangxi Zhuang Autonomous Region, Yunnan Province, Xinjiang Uygur Autonomous Region and Henan provinces) from January 1, 2011 to December 31, 2012. According to the main factors, modeling-intervention strategies and measures on reduction HIV transmission among serodiscordant couples were formed. Results: Data from the present proportion of consistent condom use (85%) modeling and the coverage of antiretroviral treatment (60%) showed that, the proportion of cumulative seroconversion among the spouses was 1.76%. Results from the sensitivity analysis on modeling the consistent condom use and the antiretroviral treatment showed that, when the coverage of antiretroviral treatment was as 90% and the proportion of consistent condom use increased from 50% to 90%, with 80.7% of the risk of spouse seroconversion could be reduced. Or, when the proportion of consistent condom use was as 90% and the coverage of antiretroviral treatment increased from 50% to 90%, with 64.5% of the risk of spouse seroconversion could be reduced. Conclusions: With measures as consistent condom use plus provision of timely antiretroviral therapy to HIV positive index spouses, the risk of sexual transmission among sero-discordant couples could be greatly reduced.
Anti-Retroviral Agents/therapeutic use*
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China/epidemiology*
;
Condoms
;
Female
;
HIV Infections/virology*
;
HIV Seronegativity
;
HIV Seropositivity/epidemiology*
;
Humans
;
Male
;
Safe Sex
;
Sexual Behavior/statistics & numerical data*
;
Sexual Partners
;
Spouses
8.Effect of baseline CD(4)(+) T cell count on drop-out of antiretroviral therapy in HIV infected persons in Guangxi Zhuang Autonomous Region, 2008-2015.
X H LIU ; Q Y ZHU ; J M SU ; Q MENG ; X J ZHOU ; Z Y SHEN ; Z Z TANG ; W M YANG ; Y H RUAN ; Y M SHAO
Chinese Journal of Epidemiology 2018;39(9):1216-1221
Objective: To investigate the effect of baseline CD(4)(+) T cell count (CD(4)) on drop-out of antiretroviral therapy (ART) in HIV infected persons. Methods: Retrospective cohort was conducted in this study. HIV infected persons aged≥18 years and receiving free ART for the first time in Guangxi Zhuang Autonomous Region (Guangxi) from 2008 to 2015 were selected from the antiretroviral treatment database of National Comprehensive HIV/AIDS Information System, with follow-up conducted till May 30, 2016. Cause-specific Cox proportional hazard models were used to evaluate effect of different CD(4) on the drop-out of ART in the HIV infected persons. Results: A total of 58 502 eligible study participants were included in this retrospective cohort study. The average drop-out ratio was 4.8/100 person-years. After controlling the following baseline covariates: age, sex, marital status, route of HIV infection, WHO clinical stage before ART, initial/current ART regiment, ART regiment adjustment, and year of initiating ART for potential confounding, the adjusted HR of drop-out for HIV infected persons with 200- cells/μl, 351-cells/μl and ≥500 cells/μl were 1.110 (95%CI: 1.053-1.171, P<0.001), 1.391 (95%CI: 1.278-1.514, P<0.001) and 1.695 (95%CI: 1.497-1.918, P<0.001), respectively, in risk for drop-out compared with those with baseline CD(4)<200 cells/μl. Among the HIV infected persons, 56.0% (1 601/2 861) of drug withdrawal was due to poor compliance with medication. Conclusions: With the increase of baseline CD(4) when initiating ART, the risk for the drop-out in HIV infected persons increased significantly. To further reduce the drop-out of ART, it is important to take CD(4) into account in initiating ART and to strengthen the health education on treatment compliancy and training for healthcare providers.
Adolescent
;
Anti-Retroviral Agents/administration & dosage*
;
CD4 Lymphocyte Count
;
China/epidemiology*
;
HIV
;
HIV Infections/virology*
;
Humans
;
Incidence
;
Medication Adherence
;
Retrospective Studies
;
T-Lymphocytes
9.Impact of HIV and Mycobacterium tuberculosis co-infection on related mortality.
Z G ZHENG ; W K GENG ; Z Z LU ; J J LI ; C X ZHOU ; W M YANG
Chinese Journal of Epidemiology 2018;39(10):1362-1367
Objective: To understand the impact of HIV and Mycobacterium tuberculosis (MTB) co-infectious (HIV/MTB) on related mortality in Guangxi Zhuang Autonomous Region, provide evidence for the development of a better HIV/MTB co-infection control and prevention program. Methods: A multiple cross-systems check (MCSC) approach was used to confirm the HIV/MTB co-infection individuals on data related to treatment, follow-up, epidemiological comprehensive and Tuberculosis (TB) special report system. Social demography characteristics, incidence of TB among HIV positive individuals, HIV incidence among MTB infection persons etc., were described. We compared the mortalities and related risks between HIV/MTB co-infection and mono HIV positive individuals as well as between the HIV/MTB co-infection and mono MTB infection persons, using both the Chi Square test and the Cox's proportional hazard regression model (Cox). Results: Reported data showed that the incidence of MTB co-infection in the HIV cohort was 17.72% (2 533/14 293), while HIV incidence in the TB patients was 5.57% (2 351/42 205), respectively. The mortality of HIV/MTB co-infection in the HIV/AIDS cohort was 15.16% (384/2 533) within one-year of observation and was significantly higher than the mortality (13.63%,1 603/11 760) of mono HIV positive individuals (P<0.000 1). The percentage of the HIV/AIDS death cases was 19.33% (384/1 987) who registered and died in the 2011 calendar year were caused by MTB co-infection. Among all the HIV/MTB co-infection patients who had been identified from the HIV cohort, 60.05% (1 521/2 533) had initiated ART, 15.48% (392/2 533) had been cured for TB and 27.48% (696/2 533) had been under complete TB regimen. Among the confirmed HIV/MTB cases from the TB cohort, the cure rate of TB was 19.70% (463/2 351) and the percentage of completed TB regimen was 37.26% (876/2 351). The percentage of the individuals whose CD(4)(+) T lymphocyte cells count appeared less than 200 cell/μl was 64.13% (785/1 224), upon the HIV diagnoses were made. Compared with individuals who were under mono HIV infection, the mortality risk on HIV/MTB co-infection was 1.17 times higher during the five-year observation period, then the patients with only mono MTB infection and the mortality risk in patients with HIV/MTB co-infection was 25.68 times higher under the 12-month observation period. Conclusions: Both the incidence and mortality of HIV/MTB appeared high in Guangxi, with mortality and the risk of mortality in the HIV/MTB co-infection group significantly higher than that in both the HIV mono infection and the MTB mono infections groups. Both the rate of antiretroviral treatment coverage and the cure rate of TB treatment should be increased in no time as well as the capability of early TB case-finding among people living with HIV.
China/epidemiology*
;
Coinfection/epidemiology*
;
Female
;
HIV
;
HIV Infections/virology*
;
Humans
;
Male
;
Mycobacterium tuberculosis
;
Tuberculosis/virology*
10.Prevalence and associated risk factors on preterm birth, low birth weight, and small for gestational age among HIV-infected pregnant women in Hunan province, 2011-2017.
H X LI ; J F ZHENG ; G W HUANG ; J XIAO ; H WANG ; M YANG ; N FENG
Chinese Journal of Epidemiology 2018;39(10):1368-1374
Objective: To describe the prevalence of preterm birth (PB), low birth weight (LBW), and small for gestational age (SGA) among HIV-infected pregnant women and to identify associated risk factors in Hunan province. Methods: This study appeared a retrospective one on HIV-infected pregnant women retrieved from Information System of Prevention of Mother-to-child Transmission of HIV management in Hunan province, between January 2011 and December 2017. Information regarding demographic characteristics, pregnancy, antiretroviral therapy (ART), husbands/partners' relevant situation and pregnancy outcomes, among these HIV-infected pregnant women were collected and analyzed. The incidence rates on PB, LBW and SGA were calculated. Multivariate logistic regression was used to analyze the associated risk factors. Results: A total of 780 HIV-infected pregnant women were enrolled. The prevalence rates on PB, LBW and SGA in HIV- infected pregnant women appeared as 7.9% (62/780), 9.9% (77/780) and 21.3% (166/780), respectively. Results from the multivariate logistic regression analysis showed that factors as pregnancy related diseases as moderate/severe anemia, hypertensive, initial time of ART <14 gestational weeks (compared to those women without ART during pregnancy) and husbands/partners' age >35 years old (compared to husbands/partners' age 26-30 years old) etc., were associated with an increased risk of PB with adjusted OR as 4.59 (95%CI: 1.51-13.95), 4.90 (95%CI: 1.56-15.46), 2.40 (95%CI: 1.26- 4.56) and 2.29 (95%CI: 1.21-4.36). For LBW, pregnancy moderate/severe anemia, pregnancy HBV infection and initial time of ART <14 gestational weeks were associated with an increased risk of LBW, with adjusted OR as 3.28 (95%CI: 1.13-9.54), 4.37 (95%CI: 1.42-13.44) and 2.68 (95%CI: 1.51-4.76), respectively. For SGA, pregnancy HBV infection and initial time of ART <14 gestational weeks were risk factors for SGA, with adjusted OR as 4.41 (95%CI: 1.43-13.63) and 2.67 (95%CI: 1.51-4.73), respectively. Conclusion: Preterm birth, LBW and SGA were common adverse pregnancy outcomes for HIV-infected pregnant women and were associated with factors as pregnancy complications, ART and husbands/partners' age.
Adult
;
Birth Weight
;
Child
;
China/epidemiology*
;
Female
;
Gestational Age
;
HIV Infections/epidemiology*
;
Humans
;
Infant, Low Birth Weight
;
Infant, Newborn
;
Infant, Small for Gestational Age
;
Pregnancy
;
Pregnancy Complications, Infectious/virology*
;
Premature Birth/etiology*
;
Prevalence
;
Retrospective Studies
;
Risk Factors

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