Recent observations on HIV type-1 infection in the genital tract of men and women

Introduction The ultimate success of strategies to prevent sexual transmission of HIV depends, in part, on a better understanding of the virological and immunological mechanisms that define sexual transmission 1. Our understanding of HIV-1 shedding in the female genital tract has increased greatly since the publication of the last AIDS comprehensive reviews of HIV shedding in the genital tract 2,3. Here we review the literature published over the last 5 years, including virological, microbiological and immunological parameters that affect HIV-1 pathogenesis and transmission. Although several biological and behavioral factors influence the sexual transmission of HIV, this review focuses on the genital and systemic factors that define the infectiousness of HIV and susceptibility to sexual transmission 4,5. Throughout, we compare HIV-1 shedding in the genital tract of women versus men. Evaluation of virological and immunological parameters in the genital tract HIV was first isolated from the genital tract of men 6,7 and women 8,9 approximately 15 years ago. Between 1988 and 1995, only 15 and five reports, respectively, described detection of HIV in the genital tract of men and women 2. Additionally, there were few confirmed correlates of HIV-1 shedding in the genital tract for either men or women, although more was known about men 2. Female genital tract Anatomical considerations and source of HIV shedding Although HIV can be recovered from the vagina of women who have had a total hysterectomy, most genital virus arises from the cervix and possibly the upper genital tract 10–14. The proximity to the vaginal lumen of cervical-stroma lymphocytes, which compose the genital-associated lymphoid tissue, probably contributes both to HIV shedding and to susceptibility to mucosal transmission. Moreover, there are important histologic changes in the lower reproductive tract over a woman's reproductive life that influence the choice of sampling methods to evaluate HIV shedding. The cervical surface epithelium and underlying stromal inflammatory-cell constituents of the endo- and exocervix change throughout a woman's lifetime as a result of hormonal, physical and infectious influences. The squamocolumnar junction (Figs 1 and 2a) may lie exposed on the surface of the exocervix at menarche (ectropion, Fig. 2b), in most adolescent women and in almost all women following parity 15. The squamocolumnar junction recedes up into the endocervical canal during the reproductive years and has completely receded by the time of menopause. This recession occurs by replacement (metaplasia) of the ectropion columnar epithelium with squamous epithelium to form the biologically important epithelial transformation zone known about the HIV shedding or susceptibility to HIV and the epithelial transformation zone and of a woman's reproductive life the of has with increased for transmission of HIV and cervical has with increased cervical shedding of HIV adolescent cervix the of several important of epithelium that to the in squamocolumnar junction of cervical and cervical transformation zone the squamocolumnar junction and that of which by the of from of the squamocolumnar junction and transformation are of and that may HIV shedding or susceptibility to HIV from The exocervix the or cervical completely with of the vaginal squamous epithelium The from the columnar epithelium of the to the squamous epithelium of the exocervix and the squamocolumnar junction approximately of adolescent women, the squamocolumnar junction at the 15. The squamous epithelium to by and with of the The endocervical approximately by columnar epithelium that on a of the columnar epithelium form the of the endocervical tissue, there the columnar epithelial that the cervical lumen or The columnar epithelium with and The of the cervix of with of and and and and physical factors the and of the which in of the endocervical columnar epithelium the in most and women, the to a the surface to form the endocervical columnar ectropion 15. This the squamocolumnar junction the there of the endocervical ectropion the in the the ectropion by squamous epithelium to form cervical transformation zone that for Fig. this of the squamocolumnar junction and columnar epithelium of the ectropion to the of the vaginal the of HIV known for HIV of the exocervix in to and infectious of ectropion are (metaplasia) by the of squamous epithelium the columnar epithelium or and squamous of to define of Fig. epithelium the columnar epithelium of the ectropion to form the cervical transformation zone with a squamocolumnar junction the squamocolumnar junction the cervical the transformation zone and the by the time of this the squamous epithelium may the columnar and the to form the are by columnar endocervical The of the cervical transformation zone may be with a in the epithelial and which of of are with that infectious either the squamous epithelium or the columnar epithelium with epithelial and a the columnar epithelial and with lymphoid a and with in the cervical lumen epithelial from of and the and underlying to the of the endocervical canal lumen or vaginal squamous epithelium to and completely endocervical columnar epithelium by increased both to the physical to HIV during the of the on the of to of the shedding from the female genital tract during the and during of the have that are with increased of to the exocervix as a result of sexual and of the ectropion with to may have epithelial in both columnar and by a of and with of stromal into the epithelial This from the and stromal with the of and lymphoid in proximity to in the endocervical lumen or vaginal susceptibility to HIV women with women with are to have increased shedding of HIV from the genital infectiousness of the female genital tract for HIV methods for the female genital tract have with or of the cervix sampling methods have of cervical and The of the that the and of a of genital from a as the vaginal or exocervix with or of the epithelial of the female genital tract for The of sampling as approximately of up to the are sampling with of and the into of more of the sampling in has for sampling mucosal with the the that has for of cervical the of virus or and the detection of lower of virus or be in the more of The for and and including which and The can be most from the since a known up to the of sampling methods and have the of and can be into and Moreover, can be in the and the for virological or immunological of either or The of that virus and be and The can be by to the This has on has to both and as and on the mucosal and the in to for and of genital sampling of a of the sampling and biological in the in female genital tract parameters has only for HIV-1 for and for for and and this that for HIV-1 which to The the for a known of the which the of the to more sampling may be in the of sampling on the sampling by may sampling by the to sampling has to from the to the most and of virus in the cervix and in the vagina genital tract to the lower female genital the genital tract to the detection and of HIV-1 in have of HIV in men. and in a that with The lymphocytes, and epithelial up of from the and more The of from the and the of on and of of HIV in from The and of and were by and The detection of HIV in the was from of the the biological of and contributes to and in for HIV, the infectiousness of the HIV in in the cervix and the of the genital tract be HIV and in Although and in HIV, there that are with virus in may HIV transmission by with virus to possibly of with the of the genital has and the to transmission of and virus in both of virus are literature in about the and source of HIV in for reproductive for have confirmed that HIV in are lower and more in a of virus and in and to that and are at all of the reproductive most in the The of has for HIV in the of men and in which a more source of HIV of genital tract virus HIV have HIV-1 from and in there HIV-1 can be as or virus for women, HIV-1 are in and and in The to HIV-1 in the female and genital a of the of from to have that in of in of and in of from men over that genital was in of in of and in of are in in the genital from men and to increased HIV have in endocervical or and in HIV in and genital are and women and men. for cervical canal and for to the of of in or more of men Although the for this several that this can be by with or of HIV were in from women over the HIV detection from cervical and vaginal has the HIV-1 was more in endocervical versus vaginal versus although detection was for by either was with detection by the and with and HIV-1 have a of was in and of and respectively, and was in and of of HIV was in of HIV was in of and of HIV The of detection of either or in the female genital in in the of virus has from and The methods have to in of the of virus The of virus only at a to be as with HIV-1 the of with sampling up to of women may be HIV more from the genital tract from the female genital of the virus recovered from the and from the and HIV of correlates with HIV in tract immunological Female to evaluate parameters in the female genital tract have of and in genital tract as as of The most have in the genital tract and the and methods has to cervical for The of methods have that to HIV in the female genital with to have that the and in cervical have with of and have that the of in from women correlates with for from the female genital tract are most either or were the methods be with of the in and sampling has to the of and and can both be with in there of HIV or and to have of in this have on from the female genital and have in cervical and vaginal from the cervical have more both have a and the of have in cervical mucosal in with underlying genital tract The of a of on be important for the transmission of HIV Evaluation of parameters in the genital tract has of of and and in the of and in more are to factors in including can affect the of and be and are at in methods as are methods be to evaluate The of total in to be lower total in both and men there of of or and are in most lower of are have in and that and can be in from both and men can be in Evaluation of in has the of were to have have in including and from the female genital The most the to for The total and The in from the The only with was the this to the and the of have for men. of HIV-1 virus shedding in the genital tract The most genital in women and men virus The of genital that the of HIV-1 transmission and has a on the of HIV in The biological for as important in HIV transmission and pathogenesis more the of epithelial to HIV The HIV, and that in the of HIV transmission are by biological factors that may in sexual the increased shedding of HIV from and the biological and HIV have in HIV a in in the of in in and in Although the for of HIV-1 to be that may at the in by mechanisms to of the correlates for women The and HIV in of susceptibility and infectiousness have genital susceptibility to HIV more and the of genital for men. Although HIV infectiousness from men to women increased by the of that the for transmission from women to men. with HIV in women have the and of by HIV Although into the of HIV and genital have the HIV and genital in and the may on the in and were more women as were genital and vaginal and in to there was and HIV in Additionally, increased HIV has with and sexual The for increased genital HIV-1 shedding in the of genital may that the of increased of and at the of described of microbiological correlates of HIV-1 shedding in the female genital tract have in can be in to or and to in Additionally, with the microbiological may with the HIV-1 HIV-1 the review by and of the correlates of HIV-1 shedding in the female genital tract in published in the last only cervical and had with a increased of HIV-1 detection in the female genital tract microbiological correlates of HIV-1 shedding in the female genital tract in published and of that have the and HIV shedding in in shedding was in that HIV as a was in a that HIV as or men were and HIV shedding be The more on the of with on increased HIV shedding in the genital tract are from in which genital are and in women who with a the following of This that may affect and HIV shedding. The of have that of most genital in a of HIV-1 genital tract was the of by are to the of to genital HIV virus and in transmission. are for and HIV genital shedding. The of shedding from the cervix was in of women shedding of was over a in women with was in a of women a of in women The of both in the genital tract of women a better of and as for genital HIV shedding. to the in HIV following of of genital which in may the of HIV of the more of correlates of in the of to a that of HIV-1 in has with including of and to be with This to be a that HIV by a of the correlates for men as and may affect the of HIV in biological correlates of HIV shedding in the genital tract in published and and are important of HIV shedding in that genital tract are important of HIV in the for HIV-1 from increased and a The for HIV-1 detection from and a has the of and HIV in and HIV shedding in of shedding in have the of on HIV shedding to the of on are have during the for sexual transmission and the of that a of HIV may be the from the as by are to evaluate this correlates for women underlying in the female genital including and can to of the and that HIV can HIV by the of This may be important in of the HIV virus as this has to have for immunological correlates of HIV shedding are in immunological correlates of HIV shedding in the female genital tract in published and and are important for of in to of HIV are with the of which important for and for on in genital tract increased in versus women of versus women a in vaginal and in cervical from This has for the of transmission women correlates for men that have parameters and HIV in men have the that HIV in and as as and have to HIV of the in the which that have a factors with genital tract shedding of HIV HIV-1 and shedding in the genital tract has in women with and in in a to of on or genital of HIV Additionally, of and has to be with cervical detection The of either or the of female in on HIV shedding in has and genital The HIV-1 in and the of HIV-1 in the and female genital has in and HIV-1 can be in most and female genital with and in approximately of from women with have and the to virus in the genital The by the with that in from that genital HIV shedding. this of were for for and for the was the of genital shedding. HIV and genital shedding have women with genital of the that genital are in to that and are of HIV detection genital and were of genital tract HIV detection in was with a to in HIV detection in the genital The most on the of with genital HIV from women who or were for changes in genital with had HIV in the genital the and genital tract detection of virus up to of women and of men have genital tract genital tract of HIV occurs in men and in the of women and may to this have the of of virus or with genital by either or Although there parameters in and genital a of shedding from the genital The in the may result in of to genital of and in men and women that with increased in the genital as by increased shedding of and to with to there to be a to in the genital tract of on the HIV of in the genital tract from that of the of have of the mucosal in have that women who are exposed to HIV in the genital of with women have that can be isolated by cervical the female genital tract may be important for as a first of HIV transmission. The and genital tract shedding of HIV and to more of the in this were the that be in with women were to in approximately of women of the and to virus in the genital tract have that are a to HIV transmission although are to has at the of on the sexual transmission of to are may have a on the sexual transmission of HIV of genital HIV in the with into genital into the female genital tract were at the time of this the female reproductive tract at the of the to was for into the and on of the and biological mechanisms that are in have that HIV are in by this in result in a in sexual transmission of HIV Moreover, have in which and are to genital tract HIV in the genital tract that virus in the to may completely virus in the genital tract of women or men a of men and women who had for up to years, virus was in the of of men and in cervical of of women as a of virus may be in the female genital tract and in and men of the of virus with are to the of sexual transmission and virus in genital changes over the and the on HIV shedding in HIV-1 genital tract shedding women AIDS to have and of and Although in HIV are to be hormonal, the of and on HIV pathogenesis are have to of the on HIV detection in the genital tract or in HIV in a the and HIV-1 in the genital tract and that were with a in HIV The may in genital and have on of HIV in have endocervical or The of changes in of the in with the for The total of HIV in in endocervical canal on sampling changes in from the endocervical canal have during all of the with the more The HIV were only in endocervical in for were in This in endocervical HIV during the have a biological as in the vagina in are at the time of The that endocervical canal with a that of and the with the as endocervical This endocervical and only in the in which HIV was in all has the of HIV to the vaginal of virus during the This probably as of the of the on HIV-1 parameters sampling during in HIV-1 have over the for most of the in the female genital in during the of the has in only a of women have for and of Additionally, changes over the may be by the of or women, in shedding was over the a in detection was during the both were by in women changes in by the or over the was more during the in immunological parameters have changes in in the female reproductive tract during the that and are from the of women had the and from women had the during the of the The of from vaginal and cervical of the Additionally, and and in the vagina during the of by cervical and epithelial with the which may the influence of the on have the of the on parameters in in in the mucosal and systemic during the have including and and were in the genital tract with during the of the This in with increased of HIV detection in the genital to the only during the of the was The of changes in the genital tract and has for most are and in the lower female genital tract in immunological by and and epithelial immunological at throughout the genital tract of in and have that in the genital in systemic are have to have and to HIV in epithelial with the of in increased of and 1 have cervical have the of of This result with of in cervical from female the of HIV in the female genital of HIV have in men. biological of the female genital tract from HIV-1 and with to to HIV-1 a and a epithelial a of in and are microbiological that the in known about the of in and the in the female or genital Although several of have to have in and the and HIV-1 in the genital tract has have that cervical can and The and vaginal are vaginal in the of and with the with the of HIV-1 in which with the of HIV-1 with that in are in women who have with and Moreover, and the versus may the of The epithelial from which in by in the of the genital epithelial to be a of reports, from HIV this was to the of and The the HIV and has as a by which HIV may the of in women of in and are The of have have that may influence the of HIV-1 in the and the of infectious virus in which in in known to in biological including has The in in and the a of HIV-1 in in and has on the virus in the which may as at HIV-1 in and may a in HIV in the genital tract be to and and in may of and the of of to in the female reproductive tract and as a the of HIV-1 The of in are of in the and which has in The of and on the of and by the of both and HIV-1 by may to HIV-1 in by the and a few have genital tract and in the female genital tract of have to result in increased of vaginal HIV-1 HIV-1 or cervical several mechanisms by which and can The that increased shedding with in this be in the vaginal the endocervical known about the of to HIV transmission. and and are in there HIV for of HIV-1 were with for or and and for or and transmission of to in the Although virus may be in the of known virus that the female genital are for transmission of and HIV-1 and of virus by of HIV-1 on genital has that from to female at of at of versus at of and of HIV in genital are and women may HIV of in the genital tract and this may be for of the of the from the genital of in have on men and that to virus that over that women may be at the time of with of the of or at the genital women have to in men and and in HIV and Although in and more of all HIV the in to a in and a in are of that HIV-1 may with to virus in transmission and the and genital for have although and genital for men and women to be with published for have in HIV and and may the of factors as on the shedding of HIV in the genital tract The of HIV for by the of the genital tract in a either a or as a first the of HIV in the genital sexual transmission and the of the HIV female of genital with and that was mucosal to HIV that the genital tract of HIV HIV may in women in or men women are with women, that a for immunological The of a the and genital in men has that arises the of the genital in over the of may the to the of the genital tract in the or as a and transmission understanding of HIV transmission are the and the genital of or virus or both are for transmission. a in the transmission with men five more women of transmission with of and and women in the of transmission during The of to be lower in women in men in during the of the more in that in the may be more of transmission in women in men in the the of HIV-1 transmission were and genital can be by the the genital shedding of virus on and be to be of and of transmission. The in the and the of the virus may all influence the of transmission The genital of in men and women most occurs have to HIV transmission in women are for men. of squamous epithelial the female genital in the zone of the exocervix and the endocervical canal This squamous epithelial to be the to the with are to into the endocervical the columnar epithelial only a and the have and virus virus the and that the have that cervical epithelial the of or HIV, although the virus can be for a time in epithelial to be in the vaginal in approximately the Although in the genital tract have to and infectious virus in isolated from the vagina have for and of vaginal occurs with both and and occurs in the of the of in women are probably of the vaginal epithelial at the of the and the with of virus from the mucosal in to lymphoid of The of HIV transmission in versus was to be which with the transmission of HIV transmission in may be by increased which the infectiousness in more the lower of in susceptibility to of the of in the with to the or the of the there a genital genital the mucosal and HIV that the of and on the that the of transmission was from the of transmission that the was of Although there were may be by at and the of the the of be in or the lower transmission in the most men are that for be to the of in HIV transmission The HIV, the and genital are more was first The of HIV-1 in the genital tract only that there are that more to be about the of genital HIV to to the of changes in with versus and genital mucosal mechanisms in men and a more comprehensive of genital virological, immunological and parameters to a of the pathogenesis of genital tract HIV-1 and the of HIV sexual transmission. women, parameters be with the reproductive life and with and changes in the cervix and the cervical transformation zone over this life 5 several that be to the of genital and shedding and the by which at the genital following HIV and and probably at or the mucosal understanding the mechanisms of and shedding in part, on and and and the to of genital genital HIV for HIV in the genital tract of men and of sampling the female genital tract by a with HIV be to the of the woman's and reproductive life with in a genital the to genital tract or or of the female genital tract HIV and susceptibility to with the and of a woman's reproductive life the the time of into the woman's and important to the of shedding endo- versus sampling methods be that the of can be for in the probably be to or of the and HIV in men and are to the of the HIV and genital on the of genital tract and the of genital tract shedding. are to evaluate the for the and the genital The genital may be important for with of to the lymphoid This be in the and of genital may be to evaluate the and of virus the genital and and the of in are to the of and changes in in the female and genital in this and the of we can to more about HIV and over the few to the of and genital tract more are to evaluate the of or change in on changes in and genital tract the of genital tract on the of HIV and transmission in men and the time of this there was only on into the female genital are for the of and of virus from the genital tract to of to the of on and HIV of in men be factors that may influence HIV shedding in the and female genital and be with to on and that and a to understanding of the pathogenesis of HIV in the genital of men and of and immunological parameters and be for understanding the success or of be important for the of reproductive for be as of to and of and for and of and of for and for This was in by and the of for AIDS