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At least 397 records · Page 22Linked to original sources
PubMed2004

Clinical, immunological and virological evolution in patients with CD4 T-cell count above 500/mm3: is there a benefit to treat with highly active antiretroviral therapy (HAART)?

To assess the clinical, immunological and virological evolution in HIV-1 infected patients with CD4 T-cell count above 500/mm3, a historical cohort of 202 untreated and 96 patients treated with HAART was longitudinally studied (median follow-up 36 months). Fourteen untreated and 2 treated patients experienced clinical progression (p = 0.09). The difference between baseline CD4 T-cell count and after 3 years, was -240/mm3 in the untreated group +19/mm3 in the HAART group (p < 10(-3)). A better immunological outcome was significantly associated with a HIV sexual contamination (p = 0.01), HAART (p = 0.01), high baseline CD4 T-cell count (p < 10(-3)) and low baseline HIV viral load (p = 0.01). In the HAART group, the incidence rate of antiretroviral modification due to tolerance difficulties was 0.23+/-0.36/patient year. A sustained undetectable HIV viral load was correlated with a low baseline HIV viral load (p = 0.003) and to be antiretroviral naive (p < 10(-3)). Thus, HAART provide a better immunological outcome in patients with high CD4 T-cell count. However, the CD4 decay slope after 3 years, the risk of therapeutic side-effects and the low risk of clinical progression do not support systematic treatment of those patients.

Adult↗
PubMed2002

The selection and evolution of viral quasispecies in HIV-1 infected children.

OBJECTIVES: To analyse the diversity and divergence of the viral populations in three mother-child pairs in longitudinally obtained samples for up to 7 years. METHODS: Peripheral blood mononuclear cells were obtained from three mothers at delivery and three to four samples were obtained from each of their children from 1.5 months up to 78 months of age. The V3 region of HIV-1 was amplified by polymerase chain reaction, cloned and sequenced. HIV-1 DNA sequence comparisons were performed by phylogenetic analysis. RESULTS: The viral population was initially homogenous in two children but highly heterogeneous in one child. Three patterns of vertical transmission seemed to have occurred: transmission of the most prevalent maternal strain, of a minor maternal strain and of multiple maternal strains. In one child, a possible reappearance of a maternal sequence was observed at 34 months of age. CONCLUSIONS: Children may become infected with the most prevalent maternal strain, a minor maternal variant or multiple maternal quasispecies. Maternal viral variants may reappear in children after several years of infection and could possibly be derived from a reservoir of founder quasispecies established during the children's primary HIV-1 infection.

Adult↗
PubMed2004

The role of viral coreceptors and enhanced macrophage tropism in human immunodeficiency virus type 1 disease progression.

Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the long-term pathogenesis of HIV-1 infection. Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in approximately 40 to 50% of infected individuals. However, the majority of infected individuals who progress to AIDS harbour only CCR5-dependent (R5) viral strains. The progression of HIV-1 disease is associated with an enhanced tropism of R5 viral strains for monocyte/macrophage lineage cells (enhanced M-tropism). However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown. This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1. We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilise relatively low levels of CCR5 expressed on macrophages, by way of increased CCR5 affinity. The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss. These variants are likely to impact HIV-1 disease progression, especially in patients who persistently harbour only R5 viral strains.

CD4-Positive T-Lymphocytes↗
PubMed1994

Evolution of drug-resistant tuberculosis: a tale of two species.

The history of the disease tuberculosis is briefly discussed. Now human societal failures have potentiated the evolution of drug-resistant strains of the tubercle bacillus in the United States and around the world. Until recently, this evolutionary change largely posed a threat to the health and survival of the individual in whom inadequate therapy promoted the drug resistance. However, the human immunodeficiency virus epidemic threatens to promote wholesale transmission of multidrug-resistant tuberculosis with the potential for immense morbidity and mortality. Reinforced treatment and control programs for tuberculosis are vital.

Biological Evolution↗
PubMed2004

Effect of perinatal zidovudine prophylaxis on the evolution of cell-free HIV-1 RNA in breast milk and on postnatal transmission.

Perinatal zidovudine (ZDV) prophylaxis decreases rates of perinatal transmission of human immunodeficiency virus type 1 (HIV-1). Its relationship with levels of HIV-1 RNA in breast milk and postnatal transmission in breast-fed African children is unknown. At day 8 after delivery, levels of HIV-1 RNA in breast milk from 28 women who transmitted HIV-1 (Ts) postnatally and from 130 women who did not transmit HIV-1 (NTs) were lower for women receiving ZDV than for women receiving placebo. Levels of HIV-1 RNA in breast milk remained low over time in NTs but increased by 8-16-fold in Ts treated with ZDV from baseline to days 45/90 after delivery. Levels of HIV-1 RNA in breast milk at day 8 after delivery and the increase in levels of HIV-1 RNA in breast milk from day 8 to days 45/90 after delivery were independently associated with postnatal transmission. An increase in the levels of HIV-1 RNA in breast milk from day 8 to 45 after delivery was associated with maternal ZDV prophylaxis. The rebound in levels of HIV-1 RNA in breast milk after discontinuation of maternal antiretrovirals needs to be further explored--it may justify prolonging antiretroviral prophylaxis during the entire breast-feeding period.

Africa↗
PubMed1994

Evolution of immunological abnormalities in HIV infection by vertical transmission.

Forty-four children infected through vertical transmission, from a total of 146 born to HIV-positive mothers, were studied. Immunological data were analysed and compared with those of the noninfected children. Two transmission patterns emerge from the clinical and immunological characteristics: (i) infants infected during pregnancy with severe immunodeficiency and clinical manifestations before the age of 1 year, and (ii) children probably infected perinatally, who have better clinical outcome. Immunological data are important for prognosis and early therapeutic protocols to be established.

CD4-Positive T-Lymphocytes↗
PubMed2004

Forced selection of a human immunodeficiency virus type 1 variant that uses a non-self tRNA primer for reverse transcription: involvement of viral RNA sequences and the reverse transcriptase enzyme.

Human immunodeficiency virus type 1 uses the tRNA(3)(Lys) molecule as a selective primer for reverse transcription. This primer specificity is imposed by sequence complementarity between the tRNA primer and two motifs in the viral RNA genome: the primer-binding site (PBS) and the primer activation signal (PAS). In addition, there may be specific interactions between the tRNA primer and viral proteins, such as the reverse transcriptase (RT) enzyme. We constructed viruses with mutations in the PAS and PBS that were designed to employ the nonself primer tRNA(Pro) or tRNA(1,2)(Lys). These mutants exhibited a severe replication defect, indicating that additional adaptation of the mutant virus is required to accommodate the new tRNA primer. Multiple independent virus evolution experiments were performed to select for fast-replicating variants. Reversion to the wild-type PBS-lys3 sequence was the most frequent escape route. However, we identified one culture in which the virus gained replication capacity without reversion of the PBS. This revertant virus eventually optimized the PAS motif for interaction with the nonself primer. Interestingly, earlier evolution samples revealed a single amino acid change of an otherwise well-conserved residue in the RNase H domain of the RT enzyme, implicating this domain in selective primer usage. We demonstrate that both the PAS and RT mutations improve the replication capacity of the tRNA(1,2)(Lys)-using virus.

Amino Acid Substitution↗
PubMed2005

Clinical characteristics and evolution of syphilis in 24 HIV+ individuals in Rio de Janeiro, Brazil.

A total of 24 patients with syphilis and HIV infection were treated from January 1997 to March 2003 at the Infectious Dermatology Outpatient Clinic of the Evandro Chagas Clinical Research Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. The caseload consisted of 20 males (83.3%) and four females (16.7%), with a mean age of 38.04 years and mean T CD4+ count of 389.5 cells/mL. Syphilis was diagnosed as secondary in 16 (62.5%) patients, late latent in eight (33.3%), and tertiary in one (4.2%). Manifestations of secondary syphilis were palmar and plantar erythematopapulous cutaneous lesions in nine (37.5%), papulous exanthema in four (16.7%), patchy alopecia in 3 (12.5%) and osteochondritis in one patient (4.2%). Tertiary syphilis was characterized by verrucous lesions. Neurosyphilis was diagnosed in four patients (16.7%), with headache as the only manifestation in two patients. Drugs used in treatment included benzathine penicillin, ceftriaxone, erythromycin, and crystalline penicillin. Cure was achieved in 18 patients (75%). Five patients (20.8%) were retreated, three of whom presented a history of re-exposure. This study confirms the importance of establishing the diagnosis of neurosyphilis in patients with HIV infection, in addition to performing follow-up on treatment for syphilis.

Adult↗
PubMed2005

Pathogenesis of macrophage tropic HIV-1.

Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the pathogenesis of HIV-1 infection. Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in approximately 40 to 50% of infected individuals. However, the majority of infected individuals who progress to AIDS harbor only CCR5-dependent (R5) viral strains. HIV-1 disease progression is associated with an enhanced tropism of R5 viral strains for cells of the monocyte/macrophage lineage (enhanced M-tropism). However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown. This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1. We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilize relatively low levels of CD4 and CCR5 expressed on macrophages. The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss. These variants are likely to impact HIV-1 disease progression, particularly in patients who persistently harbor only R5 viral strains.

Disease Progression↗
PubMed1999

[Early decline in an epidemic: evolution of the prevalences of HIV, hepatitis B, hepatitis C and aminotransferases in intravenous drug abusers in Strasbourg between 1980 and 1990].

OBJECTIVE: In order to study the prevalence of hepatitis B and C as well as HIV virus and disruptive factors of aminotransferase enzyme among intravenous drug users. METHOD: We conducted retrospective study of 169 patients who were hospitalised in a clinic where they were weaned from drug use between 1980 and 1990. RESULTS: The prevalence of HIV is 13.2%, and that of hepatitis B is 67.5%. When comparing the years 1980-1987 and 1987-1990, we noticed that the prevalence of HIV drops from 25.9% to 7.8% (p = 0.006), and that of hepatitis B from 75.9% to 60% (p = 0.027). Since November 1989, we were able to detect hepatitis C virus on a regular basis, and it showed a prevalence of 67.4%. The prevalence of aminotransferase enzyme disorders is 52.7%. CONCLUSION: We compare these results with those of other material on the same subject and we discuss various ideas to explain the unexpected decrease of HIV prevalence.

Adult↗
PubMed1999

Significance of the human immunodeficiency virus infection in patients submitted to cardiac surgery.

BACKGROUND: To realize if cardiac surgery could interfere with the evolution of HIV infected patients to the acquired immunodeficiency syndrome (AIDS). METHODS: The study group consisted of 30 HIV positive patients (0.21%) among 14,785 who underwent cardiac surgery at the Heart Institute of University of Sao Paulo Medical School (Incor-FMUSP) from November 1988 to December 1994. Patients were followed up until they were discharged from hospital and a new contact was kept at the end of the first semester of 1995. RESULTS: All patients were asymptomatic at the time they were operated. Two patients progressed to death during hospitalization due to non-infectious complications and other three patients could not be traced. After all 25 patients had their progression evaluated. Six patients (24%) died within a period ranging from 1 to 46 months (average=17 months): 2 due to bacterial pneumonia and 04 due to AIDS-related complications. The average follow-up period for the 19 surviving patients was 33.6 months (ranging from 13 to 74 months), and only one of them (5.3%) saw the infection progress to AIDS. In summary, 5/25 (20%) saw HIV infection progress to AIDS within a maximum period of 74 months. CONCLUSIONS: Data available up to now show no conclusive evidence of acceleration of HIV into AIDS associated with cardiac surgery.

AIDS-Related Opportunistic Infections↗