Comparison of Human Immunodeficiency Virus Type 1 Viral Loads in Kenyan Women, Men, and Infants during Primary and Early Infection

ABSTRACT Steady-state levels of human immunodeficiency virus type 1 (HIV-1) RNA in plasma reached at approximately 4 months postinfection are highly predictive of disease progression. Several studies have investigated viral levels in adults or infants during primary and early infection. However, no studies have directly compared these groups. We compared differences in peak and set point plasma HIV-1 RNA viral loads among antiretrovirus-naive Kenyan infants and adults for whom the timing of infection was well defined. Peak and set point viral loads were significantly higher in infants than in adults. We did not observe any gender-specific differences in viral set point in either adults or infants. However, infants who acquired HIV-1 in the first 2 months of life, either in utero, intrapartum, or through early breast milk transmission, had significantly higher set point HIV-1 RNA levels than infants who were infected after 2 months of age through late breast milk transmission or adults who were infected through heterosexual transmission.

Download Full-text

Theoretical Design of a Gene Therapy To Prevent AIDS but Not Human Immunodeficiency Virus Type 1 Infection

Journal of Virology ◽

10.1128/jvi.77.18.10028-10036.2003 ◽

2003 ◽

Vol 77 (18) ◽

pp. 10028-10036 ◽

Cited By ~ 49

Author(s):

Leor S. Weinberger ◽

David V. Schaffer ◽

Adam P. Arkin

Keyword(s):

Gene Therapy ◽

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Antiretroviral Drugs ◽

Set Point ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Recent reports confirm that, due to the presence of long-lived, latently infected cell populations, eradication of human immunodeficiency virus type 1 (HIV-1) from infected patients by using antiretroviral drugs will be exceedingly difficult. An alternative to virus eradication may be to use gene therapy to induce a pseudo-latent state in virus-producing cells, thus transforming HIV-1 into a lifelong, but manageable, virus. Conditionally replicating HIV-1 (crHIV-1) gene therapy vectors provide an avenue for subduing HIV-1 expression in infected cells (by creating a parasite, crHIV-1, of the parasite HIV-1), potentially reducing the HIV-1 set point and delaying AIDS onset. Development of crHIV-1 vectors has proceeded in vitro, but the requirements for a crHIV-1 vector to proliferate and persist in vivo have not been explored. We expand a widely accepted mathematical model of HIV-1 in vivo dynamics to include a crHIV-1 gene therapy virus and derive a simple criterion for designing crHIV-1 viruses that will persist in vivo. The model introduces only two new parameters—HIV-1 inhibition and crHIV-1 production—and both can be experimentally engineered and controlled. Analysis demonstrates that crHIV-1 gene therapy can indefinitely reduce HIV-1 set point to levels comparable to those achieved with highly active antiretroviral therapy, provided crHIV-1 production is more efficient than HIV-1. Paradoxically, highly efficient therapeutic inhibition of HIV-1 was found to be disadvantageous. Thus, the field may benefit by shifting the search for more potent antiviral genes toward engineering optimized therapy viruses that package ultraefficiently while downregulating viral production moderately.

Download Full-text

Human Immunodeficiency Virus Type 1 Clade B Superinfection: Evidence for Differential Immune Containment of Distinct Clade B Strains

Journal of Virology ◽

10.1128/jvi.79.2.860-868.2005 ◽

2005 ◽

Vol 79 (2) ◽

pp. 860-868 ◽

Cited By ~ 61

Author(s):

Otto O. Yang ◽

Eric S. Daar ◽

Beth D. Jamieson ◽

Arumugam Balamurugan ◽

Davey M. Smith ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Vaccine Development ◽

Effective Vaccine ◽

Set Point ◽

Clade B ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Sequential infection with different strains of human immunodeficiency virus type 1 (HIV-1) is a rarely identified phenomenon with important implications for immunopathogenesis and vaccine development. Here, we identify an individual whose good initial control of viremia was lost in association with reduced containment of a superinfecting strain. Subject 2030 presented with acute symptoms of HIV-1 infection with high viremia and an incomplete seroconversion as shown by Western blotting. A low set point of viremia (∼1,000 HIV-1 copies/ml) was initially established without drug therapy, but a new higher set point (∼40,000 HIV-1 copies/ml) manifested about 5 months after infection. Drug susceptibility testing demonstrated a multidrug-resistant virus initially but a fully sensitive virus after 5 months, and an analysis of pol genotypes showed that these were two phylogenetically distinct strains of virus (strains A and B). Replication capacity assays suggested that the outgrowth of strain B was not due to higher fitness conferred by pol, and env sequences indicated that the two strains had the same R5 coreceptor phenotype. Delineation of CD8+-T-lymphocyte responses against HIV-1 showed a striking pattern of decay of the initial cellular immune responses after superinfection, followed by some adaptation of targeting to new epitopes. An examination of targeted sequences suggested that differences in the recognized epitopes contributed to the poor immune containment of strain B. In conclusion, the rapid overgrowth of a superinfecting strain of HIV-1 of the same subtype raises major concerns for effective vaccine development.

Download Full-text

Longitudinal Assessment of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Gamma Interferon Responses during the First Year of Life in HIV-1-Infected Infants

Journal of Virology ◽

10.1128/jvi.79.13.8121-8130.2005 ◽

2005 ◽

Vol 79 (13) ◽

pp. 8121-8130 ◽

Cited By ~ 41

Author(s):

Barbara L. Lohman ◽

Jennifer A. Slyker ◽

Barbra A. Richardson ◽

Carey Farquhar ◽

Jenniffer M. Mabuka ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

First Year ◽

Viral Loads ◽

Immunodeficiency Virus ◽

Ifn Γ ◽

First Year Of Life ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection results in different patterns of viral replication in pediatric compared to adult populations. The role of early HIV-1-specific responses in viral control has not been well defined, because most studies of HIV-1-infected infants have been retrospective or cross-sectional. We evaluated the association between HIV-1-specific gamma interferon (IFN-γ) release from the cells of infants of 1 to 3 months of age and peak viral loads and mortality in the first year of life among 61 Kenyan HIV-1-infected infants. At 1 month, responses were detected in 7/12 (58%) and 6/21 (29%) of infants infected in utero and peripartum, respectively (P = 0.09), and in ∼50% of infants thereafter. Peaks of HIV-specific spot-forming units (SFU) increased significantly with age in all infants, from 251/106 peripheral blood mononuclear cells (PBMC) at 1 month of age to 501/106 PBMC at 12 months of age (P = 0.03), although when limited to infants who survived to 1 year, the increase in peak HIV-specific SFU was no longer significant (P = 0.18). Over the first year of life, infants with IFN-γ responses at 1 month had peak plasma viral loads, rates of decline of viral load, and mortality risk similar to those of infants who lacked responses at 1 month. The strength and breadth of IFN-γ responses at 1 month were not significantly associated with viral containment or mortality. These results suggest that, in contrast to HIV-1-infected adults, in whom strong cytotoxic T lymphocyte responses in primary infection are associated with reductions in viremia, HIV-1-infected neonates generate HIV-1-specific CD8+-T-cell responses early in life that are not clearly associated with improved clinical outcomes.

Download Full-text

Induction of AIDS in Rhesus Monkeys by a Recombinant Simian Immunodeficiency Virus Expressing nef of Human Immunodeficiency Virus Type 1

Journal of Virology ◽

10.1128/jvi.73.7.5814-5825.1999 ◽

1999 ◽

Vol 73 (7) ◽

pp. 5814-5825 ◽

Cited By ~ 42

Author(s):

Louis Alexander ◽

Zhenjian Du ◽

Anita Y. M. Howe ◽

Susan Czajak ◽

Ronald C. Desrosiers

Keyword(s):

Human Immunodeficiency Virus ◽

Simian Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Rhesus Monkeys ◽

Consensus Sequence ◽

Viral Loads ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT A nef gene is present in all primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus of macaque monkeys (SIVmac). However, thenef genes of HIV-1 and SIVmac exhibit minimal sequence identity, and not all properties are shared by the two. Nef sequences of SIVmac239 were replaced by four independentnef alleles of HIV-1 in a context that was optimal for expression. The sources of the HIV-1 nef sequences included NL 4-3, a variant NL 4-3 gene derived from a recombinant-infected rhesus monkey, a patient nef allele, and a nefconsensus sequence. Of 16 rhesus monkeys infected with these SHIVnef chimeras, 9 maintained high viral loads for prolonged periods, as observed with the parental SIVmac239, and 6 have died with AIDS 52 to 110 weeks postinfection. Persistent high loads were observed at similar frequencies with the four different SIV recombinants that expressed these independent HIV-1 nefalleles. Infection with other recombinant SHIVnef constructions resulted in sequence changes in infected monkeys that either created an open nef reading frame or optimized the HIV-1nef translational context. The HIV-1 nef gene was uniformly retained in all SHIVnef-infected monkeys. These results demonstrate that HIV-1 nef can substitute for SIVmac nef in vivo to produce a pathogenic infection. However, the model suffers from an inability to consistently obtain persisting high viral loads in 100% of the infected animals, as is observed with the parental SIVmac239.

Download Full-text

Enhanced Secretory Leukocyte Protease Inhibitor in Human Immunodeficiency Virus Type 1-Infected Patients

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.6.808-811.1999 ◽

1999 ◽

Vol 6 (6) ◽

pp. 808-811 ◽

Cited By ~ 11

Author(s):

A. A. M. A. Baqui ◽

Timothy F. Meiller ◽

William A. Falkler

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

Protease Inhibitor ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

High Viral Load ◽

Viral Loads ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT Secretory leukocyte protease inhibitor (SLPI) has been found to possess activity against the human immunodeficiency virus type 1 (HIV-1) in vitro at physiological concentrations. A study was undertaken to evaluate SLPI levels in human saliva and plasma among HIV-positive (HIV+) patients with various HIV-1 viral loads in comparison to uninfected controls. Whole blood in EDTA and unstimulated saliva samples were collected from 37 HIV+patients, of whom 20 had a history of intravenous drug abuse (IVDA). Control samples were collected from 20 appropriate age- and sex-matched HIV-1-negative individuals. SLPI was estimated from both saliva and serum samples by an enzyme-linked immunosorbent assay. HIV viral load was determined using a quantitative reverse transcription-PCR. SLPI levels were increased 16.7% in plasma and 10.3% in saliva among HIV+ patients in comparison to uninfected controls. SLPI levels were increased 5.9% in saliva and 3.9% in plasma among HIV+ patients with a high viral load (>10,000 copies/ml) as compared to patients with a low viral load (<400 copies/ml). Only 23% of patients with a high viral load used combination therapy with protease inhibitor drugs, whereas 92.9% of HIV+ patients with a low viral load used protease inhibitors. SLPI levels did not differ significantly among the IVDA patients, patients with different viral loads, or patients using protease inhibitor drugs. There was a statistically significant increase in SLPI levels in saliva among HIV patients in comparison to non-HIV-infected controls. An increase in SLPI levels among HIV+ patients may be a natural consequence of HIV pathogenesis and an important factor in preventing oral transmission of HIV, but this increase may not be evident during plasma viremia in patients with a high viral load.

Download Full-text

Viral Tropism in Human Immunodeficiency Virus Type 1–Infected Children and Adolescents in Thailand

Journal of the Pediatric Infectious Diseases Society ◽

10.1093/jpids/piaa004 ◽

2020 ◽

Author(s):

Natt Arayapong ◽

Ekawat Pasomsub ◽

Rujikorn Kanlayanadonkit ◽

Jiraporn Keatkla ◽

Chonnamet Techasaensiri ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cd4 Cell Count ◽

Coreceptor Tropism ◽

Viral Loads ◽

Immunodeficiency Virus ◽

Treatment Naïve ◽

Hiv 1

Abstract Background Maraviroc, a C-C chemokine receptor 5 (CCR5) antagonist, has been used as an alternative antiretroviral drug in treatment-experienced adults and children infected by CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates. Prior to widespread use of this drug, rates of HIV-1 coreceptor tropism and factors associated with coreceptor tropism had to be determined. Methods HIV-1–infected individuals aged <20 years with HIV-1 viral loads >1000 RNA copies/mL who were treatment-experienced or treatment-naive were enrolled. HIV-1 coreceptor tropism was determined using a genotypic test in which V3 sequences were analyzed with GENO2PHENO version 2.5 and a false discovery rate of 5%. Results Fifty-two HIV-1–infected patients were recruited. The median age of participants was 14.9 years (interquartile range [IQR], 8.9–16.8 years). The median CD4 cell count was 396.0 cells/µL (IQR, 72.0–630.3 cells/µL). The median HIV-1 viral load was 43 339 RNA copies/mL (IQR, 8874–197 055 copies/mL). Thirty-nine patients (75%) were treatment-experienced. The most prevalent HIV-1 subtype in this population was CRF01_AE (36 patients, 69.2%). Based on analyses of V3 loop sequences, 5 of 13 treatment-naive patients (38.5%) and 11 of 39 treatment-experienced patients (28.2%) were infected by R5 viruses, while 7 of 13 treatment-naive patients (53.8%) and 19 of 39 treatment-experienced patients (48.7%) were infected by X4 viruses. The only factor associated with the presence of X4 viruses was HIV-1 subtype CRF01_AE. Conclusions X4-tropic viruses are associated with the CRF01_AE subtype. Hence, testing of HIV tropism should be performed before treatment with CCR5 inhibitors in children in areas where CRF01_AE predominates.

Download Full-text

Detection of Human Immunodeficiency Virus Type 1 (HIV-1) DNA and p24 Antigen in Breast Milk of HIV-1-Infected Ugandan Women and Vertical Transmission

PEDIATRICS ◽

10.1542/peds.98.3.438 ◽

1996 ◽

Vol 98 (3) ◽

pp. 438-444

Author(s):

Laura A. Guay ◽

David L. Hom ◽

Francis Mmiro ◽

Estelle M. Piwowar ◽

Sam Kabengera ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Breast Milk ◽

Vertical Transmission ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Immunodeficiency Virus ◽

P24 Antigen ◽

Duration Of Breastfeeding ◽

Hiv 1

Objective. To determine the correlation between the detection of human immunodeficiency virus type 1 (HIV-1) in breast milk, the duration of breastfeeding, and vertical transmission of HIV-1 infection in Ugandan women. Methods. A prospective study of HIV-1 infection in pregnant Ugandan women and their infants has been ongoing since 1990 with follow-up of mother-infant pairs for at least 2 years. Expressed breast milk specimens were collected from 201 HIV-1-seropositive and 86 HIV-1-seronegative Ugandan women approximately 6 weeks after delivery. The presence of HIV-1 DNA in the cellular fraction of the breast milk was detected by polymerase chain reaction (PCR), and HIV-1 p24 antigen was detected in the cell-free breast milk supernatant using p24 antigen enzyme immunoassay (EIA) after immune complex dissociation (ICD). The duration of breastfeeding and the clinical status of the mothers and their children were recorded. HIV-1 EIA, Western blot, PCR, or p24 antigen detection were used for the determination of the HIV-1 infection status of the children. Results. Of the 201 HIV-1-infected women studied, 47 had HIV-1-infected children, 143 had children who seroreverted, and 11 had children of indeterminate status. Breast milk supernatants were available for ICD p24 antigen testing from 188 of the HIV-1-infected women and none had detectable p24 antigen. Breast milk cell pellets were available and contained amplifiable DNA in 125 of the HIV-1-infected women (20 transmitters, 104 nontransmitters, 1 indeterminate). HIV-1 DNA was detected by PCR in 72% (75/104) of nontransmitters and 80% (16/20) of the transmitters. The duration of breastfeeding by transmitter mothers (15.8 months) was not significantly different from nontransmitter mothers (14.4 months). Conclusions. No correlation was found between the detection of HIV-1 in breast milk or the duration of breastfeeding and transmission of HIV-1 infection in this study of Ugandan women.

Download Full-text