Human immunodeficiency virus type-2 (HIV-2) is a close relative of the prototype acquired immunodeficiency syndrome (AIDS) virus, HIV-1. HIV-2 is biologically similar to HIV-1, but information is lacking concerning clinical outcomes of HIV-2-infected individuals. From 1985 to 1993, a prospective clinical study was conducted in women with HIV-2 and HIV-1 infection to determine and compare rates of disease development. HIV-1-infected women had a 67% probability of AIDS-free survival 5 years after seroconversion in contrast with 100% for HIV-2-infected women. In addition to having significantly less HIV-related disease outcome in HIV-2 enrollees compared to HIV-1 enrollees, the rate of developing abnormal CD4+ lymphocyte counts with HIV-2 infection was also significantly reduced. This natural history study demonstrates that HIV-2 has a reduced virulence compared to HIV-1.
Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.
Bacterial vaginosis (BV) was identified recently as a cofactor that promotes sexual transmission of human immunodeficiency virus (HIV). This study was done to determine if interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha could be measured consistently in cervical secretions and if high levels of these cytokines were associated with BV. Secretions were obtained from 209 study subjects; most samples had detectable levels of TNF-alpha (84.2%) and IL-1beta (79.8%). BV was detected in 53 (27.0%) of 196 women. High cytokine levels were significantly associated with BV (adjusted odds ratio [AOR], 4.17; 95% confidence interval [CI], 1.69-10.30), oral contraceptive use (AOR, 2.78; 95% CI, 1.04-7.48), and high leukocyte counts on vaginal smear (AOR, 1.18; 95% CI, 1.03-1.36). Since these cytokines could up-regulate local HIV replication through activation of the long terminal repeat promoter region, the association of BV with high levels of IL-1beta or TNF-alpha may partly explain the mechanism by which this risk factor enhances HIV transmission.
From a prospective cohort study of 1948 initially human immunodeficiency virus (HIV) uninfected female commercial sex workers followed between 1985 and 1999 in Dakar, Senegal, the authors compared the male to female per infectious sexual exposure transmission probability of HIV types one (HIV-1) and two (HIV-2). New non-parametric competing risks failure time methods were used, which minimized modelling assumptions and controlled for risk factors for HIV infection. The HIV-1 versus HIV-2 infectivity ratio over time was estimated by the ratio of smoothed non-parametric kernel estimates of the HIV-1 and HIV-2 infection hazard functions in sex workers, adjusted by an estimate of the relative HIV-1 versus HIV-2 prevalence in the partner population. HIV-1 was found to be significantly more infectious than HIV-2 throughout the follow-up period (P < 0.001). The HIV-1/HIV-2 infectivity ratio was inferred to be approximately constant over time, with estimated common value 3.55. The finding of greater HIV-1 infectivity persisted in sensitivity analyses and in covariate-adjusted analyses, with adjusted infectivity ratio estimates ranging between 3.40 and 3.86. Understanding the mechanisms by which HIV-1 infects more efficiently than HIV-2 may be useful in the development of HIV-1 vaccines. Additionally, the methodology developed here may be useful for analysing other data sets.
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