ReviewSexual transmission of HIV-1
Introduction
Approximately 2.5 million people worldwide became infected with HIV-1 in 2007 (UNAIDS, 2008). Despite downward trends in some countries, HIV-1 incidence remains high across much of Sub-Saharan Africa. In most communities affected by generalised HIV-1 epidemics, access to antiretroviral therapy (ART) is limited to those with advanced disease (Gilks et al., 2006), leaving large numbers of undiagnosed and untreated individuals at risk of transmitting HIV-1-1 to their sexual partners and offspring. At the current rate of growth of the HIV-1 epidemic, in addition to the increasing human toll, the costs of care of this growing population will become unsustainable (UNAIDS, 2008). Although condom use and behavioural interventions are capable of reducing sexual HIV-1 transmission, acceptance of these measures has been insufficient at a population level to lead to a sustained reduction in HIV-1 incidence (Mayer et al., 2008, Jewkes et al., 2008, Jewkes et al., 2006). The only proven prevention intervention is male circumcision (Auvert et al., 2005, Mills et al., 2008, Quinn, 2007, Weiss, 2007) although its wide scale implementation will be challenging (Sawires et al., 2007).
Understanding the key factors involved in the mechanisms underlying HIV-1 transmission may provide valuable incite into enhancing transmission prevention strategies. In this article we aim to review the principle factors that determine the sexual transmission of HIV-1 (Fig. 1, Fig. 2).
Section snippets
Characteristics of sexually transmitted HIV-1-1 variants
In general a homogeneous (Zhu et al., 1996, Keele et al., 2008), CCR5 using (Roos et al., 1992) non-syncytia forming variant of HIV-1 is preferentially transmitted sexually to a new host. Homogeneity of the transmitted variant is due to either a bottleneck in the transmitting person and/or selective amplification of one specific strain in the recipient (Frater et al., 2006). Although rare, transmission of a CXCR4 coreceptor utilising HIV-1-1 variant can occur (Brumme et al., 2005). Whilst many
The initial cellular targets of infection
It is likely that the initial cellular targets for HIV-1 after mucosal inoculation are either activated CD4+ T cells, dendritic cells (DCs) or macrophages (Gupta et al., 2002, Zaitseva et al., 1997). The intact thick epithelium of vagina (Gupta et al., 2002), ectocervix (Asin et al., 2009), foreskin and rectum (Meng et al., 2002) is interspersed with activated CD4 and CCR5 expressing and immature Langerhans cells (Zaitseva et al., 1997), all susceptible to HIV-1 infection. Genital DCs lie
HIV-1 plasma viral load of infected donor
Data from studies of African heterosexual HIV-1-serodiscordant couples identified that HIV-1 plasma viral load (VL) is the single most important determinant in predicting transmission; with minimal risk of onward transmission of HIV-1 when the index case plasma VL remains below 1500 HIV-1 RNA copies/ml (Quinn et al., 2000, Wawer et al., 2005, Gray et al., 2001) and each plasma VL log10 increment associated with a 2.5-fold increase in the risk of transmission (95% CI 1.85–3.26)(Gray et al., 2001
Number and nature of sex acts
The frequency, nature and duration of sexual exposure play a critical role in determining transmission of HIV-1 (Nicolosi et al., 1994, Saracco et al., 1993, Siriwasin et al., 1998). Increased duration of a relationship, higher number of sexual partners, and higher frequency of sexual contact have been associated with transmission (Mastro and Kitayaporn, 1998, Grant et al., 1987, Giesecke et al., 1992). However, the relative contribution of each of these factors governing seroconversion remains
Behavioural approaches to reduce HIV-1 transmission
Interventions to reduce unprotected sexual contact ‘unsafe sex’, target both HIV-1-negative (primary prevention) and HIV-1-positive individuals (secondary prevention). These include counselling to encourage behaviour change (increased condom use (Gorbach and Holmes, 2003), decreased numbers of sexual partners and abstinence). Condoms protect against STI and HIV-1 (Royce et al., 1997, Pinkerton et al., 1998, Malamba et al., 2005a, Malamba et al., 2005b, Ryder et al., 2000, Hanenberg et al., 1994
Treatment of STI to prevent transmission
The prompt diagnosis and treatment of sexually transmitted infections (STIs) takes a prominent place in most risk reduction strategies (White et al., 2008), although evidence regarding the population-level effectiveness of STI treatment for HIV-1 prevention (in Africa) is equivocal. A randomized controlled trial (RCT) of improved clinic-based syndromic STI treatment in rural Tanzania was shown to reduce HIV-1 incidence in the general population by 38% and to be highly cost-effective (Wawer et
Correlates of HIV-1 protection and transmission
Through studying individuals who are exposed but remain HIV-uninfected (EU), biological mechanisms have been postulated to affect HIV-1 transmission. The different factors that underlie this observed relative resistance to HIV-1 acquisition are summarised here.
Interventions to prevent transmission
The safest, cheapest and most readily available technique to prevent sexual transmission of HIV-1 is the condom (Hira et al., 1997). The impact of condom promotion on the spread of HIV has been particularly successful in areas where sex workers contributed substantially to new HIV infections. For example, Thailand's promotion of “100% condom” use in brothels led to condom use among sex workers of more than 90%. HIV infection rates among military recruits decreased by about half, and the cases
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