High viral load in semen of human immunodeficiency virus type 1-infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors

Abstract

Seminal viral load is likely to be directly related to the sexual transmissibility of human immunodeficiency virus type 1 (HIV-1). However, it is not clear whether the level of HIV-1 in semen varies with the stage of infection and whether antiretroviral therapy reduces seminal viral load. A nucleic acid sequence-based amplification (NASBA) technique was used to quantify HIV-1 RNA as an indicator of infectious viral load in semen and blood plasma of homosexual men with different stages and durations of HIV-1 infection. The median viral load in a cross section of 34 men was 11,000 HIV-1 RNA copies/ml (range, <400 to 1.3 ؋ 10 7 copies/ml) in whole semen and 5,238 HIV-1 RNA copies/ml (range, <400 to 2.8 ؋ 10 5 copies/ml) in seminal plasma, which is 10-to 1,000-fold higher than previous estimates. Viral loads in whole semen and seminal plasma were strongly correlated with blood plasma viral load (P < 0.001) but not with blood CD4 ؉ T-cell count (P ‫؍‬ 0.420). Longitudinal analysis of eight subjects who progressed to AIDS showed that seminal viral load increased in most cases, with viral load consistently higher in blood plasma than in semen. Viral loads in semen and blood plasma decreased markedly in six other patients following initiation of potent combination therapy with a protease inhibitor (indinavir) and a nonnucleoside reverse transcriptase inhibitor (DMP-266). These findings have important implications for the biology of sexual transmission of HIV-1 and its potential reduction by antiretroviral therapy.

How virus size and attachment parameters affect the temperature sensitivity of virus binding to host cells: Predictions of a thermodynamic model for arboviruses and HIV

“…Dividing 10 5 HIV virions in 10 -6 dm 3 by the Avogadro number gives [V total ] = 1.7 x 10 -13 M. The advantage of using a high V total that greatly exceeds C total is that as previously demonstrated by Gale (2018) not only may the fraction, F cT , of CD4 + T cells with bound HIV be calculated from Equation 13 with [V free ] ~ [V total ] but also any complications of handling stochastic effects at low virus doses are avoided. It is recognised that the HIV concentration at 10 5 HIV virions per mm 3 used in this model is 10-fold to 100-fold higher than that expected in a recipient person's blood present in the capillaries lining the skin at the wound site where semen or blood from an infected source were introduced since maximum human plasma and human semen HIV loadings are in the region of 13,000 copies per mm 3 and 1,800 copies per mm 3 respectively (Gupta et al 1997). This is not important, however, because the purpose of the models here in Figure 4, Figure 5 and Figure 6 is not to produce a realistic dose-response but to explore the effect of changing ΔC p , ΔS a_immob , n and temperature on the trend in the predicted number, C.V T , of host CD4 + T cells with bound virus.…”

Behavioral Mechanisms in HIV Epidemiology and Prevention: Past, Present, and Future Roles

“…The primary purpose of HAART is to combat the pathogenic effects of HIV replication among people who are already infected. Yet because HAART dramatically suppresses the concentration of HIV in the serum and genital secretions of treated people (Gulick et al 1997;Gupta et al 1997;Hammer et al 1997;Vernazza et al 1997), it is also believed to reduce the per-contact probability of transmitting HIV to uninfected partners (Quinn et al 2000;Gray et al 2001). These epidemiological consequences remain uncertain because any reduction in the per-contact transmission probability could be offset by increases in the duration of infectiousness and, perhaps, by changes in behavior.…”

Semen and Serum Pharmacokinetics of Zidovudine and Zidovudine‐Glucuronide in Men with HIV‐1 Infection

“…Virus recovered from semen is frequently genetically different from blood-derived HIV; specifically, they differ in the frequency and pattern of antiretroviral drug-resistant mutations. [8][9][10][11] Combination antiretroviral therapy decreases HIV RNA in semen, [12][13][14] but seminal virus may persist despite HIV RNA in plasma of fewer than 50 copies/ml. 9,15 Moreover, drugresistant HIV, including resistance to zidovudine, was sexually transmitted presumably through semen.…”