scholarly journals Intersubtype Human Immunodeficiency Virus Type 1 Superinfection following Seroconversion to Primary Infection in Two Injection Drug Users

2002 ◽  
Vol 76 (15) ◽  
pp. 7444-7452 ◽  
Author(s):  
Artur Ramos ◽  
Dale J. Hu ◽  
Lily Nguyen ◽  
Kim-Oanh Phan ◽  
Suphak Vanichseni ◽  
...  

ABSTRACT In this study, we describe two cases of human immunodeficiency virus type 1 (HIV-1) intersubtype superinfection with CRF01_AE and subtype B strains, which occurred in two injection drug users participating in a prospective cohort study in Bangkok, Thailand. In both cases, the superinfecting strain was detected by molecular and serologic analyses several weeks after complete seroconversion to the primary infection with a strain belonging to a different subtype. Superinfection occurred despite specific T-cell and humoral antibody responses to the primary virus. In both cases, cross-subtype immune responses were limited or absent prior to the second infection. These data show that, in some individuals, the quality and quantity of the immune response elicited by primary HIV-1 infection may not protect against superinfection. This finding has important implications for vaccine design. HIV-1 vaccines, at a minimum, will need to include potent, broadly protective, conserved immunogens derived from several group M subtypes.

2004 ◽  
Vol 78 (1) ◽  
pp. 94-103 ◽  
Author(s):  
Rose Tsui ◽  
Belinda L. Herring ◽  
Jason D. Barbour ◽  
Robert M. Grant ◽  
Peter Bacchetti ◽  
...  

ABSTRACT Evidence for human immunodeficiency virus type 1 (HIV-1) superinfection was sought among 37 HIV-1-positive street-recruited active injection drug users (IDUs) from the San Francisco Bay area. HIV-1 sequences from pairs of samples collected 1 to 12 years apart, spanning a total of 215 years of exposure, were generated at p17 gag, the V3-V5 region of env, and/or the first exon of tat and phylogenetically analyzed. No evidence of HIV-1 superinfection was detected in which a highly divergent HIV-1 variant emerged at a frequency >20% of the serum viral quasispecies. Based on the reported risk behavior of the IDUs and the HIV-1 incidence in uninfected subjects in the same cohort, a total of 3.4 new infections would have been expected if existing infection conferred no protection from superinfection. Adjusted for risk behaviors, the estimated relative risk of superinfection compared with initial infection was therefore 0.0 (95% confidence interval, 0.00, 0.79; P = 0.02), indicating that existing infection conferred a statistically significant level of protection against superinfection with an HIV-1 strain of the same subtype, which was between 21 and 100%.


2008 ◽  
Vol 82 (18) ◽  
pp. 9206-9215 ◽  
Author(s):  
Kok Keng Tee ◽  
Oliver G. Pybus ◽  
Xiao-Jie Li ◽  
Xiaoxu Han ◽  
Hong Shang ◽  
...  

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) CRF08_BC and CRF07_BC are two major recombinants descended from subtypes B′ and C. Despite their massive epidemic impact in China, their migration patterns and divergence times remain unknown. Phylogenetic and population genetic analyses were performed on 228 HIV-1 sequences representing CRF08_BC, CRF07_BC, and subtype C strains from different locations across China, India, and Myanmar. Genome-specific rates of evolution and divergence times were estimated using a Bayesian Markov chain Monte Carlo framework under various evolutionary models. CRF08_BC originated in 1990.3 (95% credible region [CR], 1988.6 to 1991.9) in Yunnan province before spreading to Guangxi (south) and Liaoning (northeast) around 1995. Inside Guangxi region, the eastward expansion of CRF08_BC continued from Baise city (west) to Binyang (central) between 1997 and 1998 and later spread into Pingxiang around 1999 in the south, mainly through injecting drug users. Additionally, CRF07_BC diverged from its common ancestor in 1993.3 (95% CR, 1991.2 to 1995.2) before crossing the border into southern Taiwan in late 1990s. Phylogenetic analysis indicates that both CRF08_BC and CRF07_BC can trace their origins to Yunnan. The parental Indian subtype C lineage likely entered China around 1981.2 (95% CR, 1976.7 to 1985.9). Using a multiple unlinked locus model, we also showed that the dates of divergence calculated in this study may not be significantly affected by intrasubtype recombination among different lineages. This is the first phylodynamic study depicting the spatiotemporal dynamics of HIV/AIDS in East Asia.


Pteridines ◽  
1990 ◽  
Vol 2 (3) ◽  
pp. 161-164 ◽  
Author(s):  
Peter Mayr ◽  
Dietmar Fuchs ◽  
Lothar C. Fuith ◽  
Gilbert Reibnegger ◽  
Ernst R. Werner ◽  
...  

Summary Eleven mothers of 12 infants with human immunodeficiency virus type 1 (HIV-1) infection (all intravenous drug users) were followed throughout their pregnancies for evidence of clinical and immunological abnormalities. Intrauterine death occurred in one, growth retardation in 7/12 pregnancies. Moderate progression of HIV-l infection according to the Walter Reed Staging Classification was observed in 5/ 11 women during pregnancy. Two of them developed AIDS during follow up after delivery. Mean neopterin levels in the first, second and third trimester were significantly higher as compared to HIV-l seronegative pregnant women. Furthermore, concentrations of urinary neopterin increased significantly with the time of pregnancy in all HIV-1 seropositive women. Since higher urinary neopterin concentrations are predictive for more rapid disease progression in HIV infected patients the data may indicate that pregnancy increases the risk for developing AIDS. However, a possible influence of continuous drug use has to be considered.


2003 ◽  
Vol 77 (1) ◽  
pp. 685-695 ◽  
Author(s):  
Rongge Yang ◽  
Shigeru Kusagawa ◽  
Chiyu Zhang ◽  
Xueshan Xia ◽  
Kunlong Ben ◽  
...  

ABSTRACT We identified a new class of human immunodeficiency virus type 1 (HIV-1) recombinants (00CN-HH069 and 00CN-HH086) in which further recombination occurred between two established circulating recombinant forms (CRFs). These two isolates were found among 57 HIV-1 samples from a cohort of injecting drug users in eastern Yunnan Province of China. Informative-site analysis in conjunction with bootscanning plots and exploratory tree analysis revealed that these two strains were closely related mosaics comprised of CRF07_BC and CRF08_BC, which are found in China. The genotype screening based on gag-reverse transcriptase sequences of 57 samples from eastern Yunnan identified 47 CRF08_BC specimens (82.5%), 5 CRF07_BC specimens (8.8%), and 3 additional specimens with the novel recombinant structure. These new “second-generation” recombinants thus constitute a substantial proportion (5 of 57; 8.8%) of HIV-1 strains in this population and may belong to a new but yet-undefined class of CRF. This might be the first example of CRFs recombining with each other, leading to the evolution of second-generation inter-CRF recombinants.


1999 ◽  
Vol 73 (8) ◽  
pp. 6453-6459 ◽  
Author(s):  
Stefano Fais ◽  
Caterina Lapenta ◽  
Stefano M. Santini ◽  
Massimo Spada ◽  
Stefania Parlato ◽  
...  

ABSTRACT In a previous study, we had found that the extent of T-cell dysfunctions induced by a T-tropic strain of human immunodeficiency virus type 1 (HIV-1) in SCID mice reconstituted with human peripheral blood lymphocytes (hu-PBLs) (hu-PBL-SCID mice) was related to the in vivo state of activation of the human lymphocytes. In this article, we compared the effect of infection of hu-PBL-SCID mice with either T-tropic (X4) or M-tropic (R5) strains of HIV-1 by performing virus inoculation at either 2 h or 2 weeks after the hu-PBL transfer, when the human T cells exhibited a marked activation state or a predominant memory phenotype, respectively. A comparable level of infection was found when hu-PBL-SCID mice were challenged with either the SF162 R5 or the IIIB X4 strain of HIV at 2 h postreconstitution, while at 2 weeks, the R5 virus infection resulted in a higher level of HIV replication than the X4 virus. The R5 strain induced a marked human CD4+ T-cell depletion along with a drop in levels of human immunoglobulin M in serum and release of soluble factors at both infection times, while the X4 virus induced severe immune dysfunctions only at 2 h. Of interest, injection of hu-PBLs into SCID mice resulted in a marked up-regulation of CCR5 on human CD4+ T cells. The percentage of CXCR4+cells did not change after transplantation, even though a significant decrease in antigen expression was observed. Comparative experiments with two molecular clones of HIV-1 (X4 SF2 and R5 SF162) and two envelope recombinant viruses generated from these viruses showed that R5 viruses (SF162 and the chimeric env-SF162-SF2) caused an extensive depletion of human CD4+ T cells in SCID mice at both 2 h and 2 weeks after reconstitution, while the X4 viruses (SF2 and the chimeric env-SF2-SF162) induced CD4 T-cell depletion only when infection was performed at the 2-h reconstitution time. These results emphasize the importance of the state of activation/differentiation of human CD4+ T cells and gp120-coreceptor interactions at the time of primary infection in determining HIV-1 pathogenicity in the hu-PBL-SCID mouse model.


2000 ◽  
Vol 74 (3) ◽  
pp. 1149-1157 ◽  
Author(s):  
Robert B. Oelrichs ◽  
Iswar L. Shrestha ◽  
David A. Anderson ◽  
Nicholas J. Deacon

ABSTRACT An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among the injecting drug user population of Kathmandu, Nepal, whose seropositivity rate has risen from 0 to 40% between 1995 and 1997. By using Catrimox to preserve whole-blood RNA at ambient temperature for transportation, HIV-1 envelope V3–V4 sequences were obtained from 36 patients in this group. Analysis of the sequences indicated a homogenous epidemic of subtype C virus, with at least two independent introductions of the virus into the population. Viral diversity was restricted within two transmission subclusters, with the majority of variation occurring in V4. Calculation of the synonymous-to-nonsynonymous mutation ratio (Ks:Ka) across this region showed that significant evolutionary pressure had been experienced during the rapid horizontal spread of the virus in this population, most strongly directed to the region between V3 and V4.


2003 ◽  
Vol 77 (23) ◽  
pp. 12921-12926 ◽  
Author(s):  
Manish Sagar ◽  
Ludo Lavreys ◽  
Jared M. Baeten ◽  
Barbra A. Richardson ◽  
Kishorchandra Mandaliya ◽  
...  

ABSTRACT Human immunodeficiency virus type 1 (HIV-1)-infected individuals develop a genetically diverse virus population over time, but often only a limited number of viral variants are transmitted from a chronic carrier to a newly infected person. Interestingly, many women but few men are infected by multiple HIV-1 variants from a single partner. To determine whether the complexity of the infecting virus population influences clinical outcome, we examined viral diversity in the HIV-1 envelope sequences present at primary infection in 156 women from Kenya for whom we had follow-up data on viral RNA levels and CD4 T-cell counts. Eighty-nine women had multiple viral genotypes, while 67 women had a single genotype at primary infection. Women who acquired multiple viral genotypes had a significantly higher viral load (median, 4.84 versus 4.64 log10 copies/ml, P = 0.04) and a significantly lower CD4+-T-cell count (median, 416 versus 617 cells/mm3, P = 0.01) 4 to 24 months after infection compared to women who were infected with a single viral genotype. These studies suggest that early HIV-1 genetic diversity is linked to faster disease progression.


2004 ◽  
Vol 78 (20) ◽  
pp. 11208-11218 ◽  
Author(s):  
Kimberly Ritola ◽  
Christopher D. Pilcher ◽  
Susan A. Fiscus ◽  
Noah G. Hoffman ◽  
Julie A. E. Nelson ◽  
...  

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) exists as a complex population of multiple genotypic variants in persons with chronic infection. However, acute HIV-1 infection via sexual transmission is a low-probability event in which there is thought to be low genetic complexity in the initial inoculum. In order to assess the viral complexity present during primary HIV-1 infection, the V1/V2 and V3 variable regions of the env gene were examined by using a heteroduplex tracking assay (HTA) capable of resolving these genotypic variants. Blood plasma samples from 26 primary HIV-1-infected subjects were analyzed for their level of diversity. Half of the subjects had more than one V1/V2 viral variant during primary infection, indicating the frequent transmission of multiple variants. This observation is inconsistent with the idea of infrequent transmission based on a small transmitting inoculum of cell-free virus. In chronically infected subjects, the complexity of the viral populations was even greater in both the V1/V2 and the V3 regions than in acutely infected subjects, indicating that in spite of the presence of multiple variants in acute infection, the virus does pass through a genetic bottleneck during transmission. We also examined how well the infecting virus penetrated different anatomical compartments by using the HTA. Viral variants detected in blood plasma were compared to those detected in seminal plasma and/or cerebral spinal fluid of six individuals. The virus in each of these compartments was to a large extent identical to virus in blood plasma, a finding consistent with rapid penetration of the infecting variant(s). The low-probability transmission of multiple variants could be the result of transient periods of hyperinfectiousness or hypersusceptibility. Alternatively, the inefficient transfer of a multiply infected cell could account for both the low probability of transmission and the transfer of multiple variants.


2008 ◽  
Vol 89 (11) ◽  
pp. 2773-2782 ◽  
Author(s):  
Ana Ceballos ◽  
Guadalupe Andreani ◽  
Chiara Ripamonti ◽  
Dario Dilernia ◽  
Ramiro Mendez ◽  
...  

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother–child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.


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