Identification of three novel human leukocyte antigen alleles, HLA-B*58:43, HLA-C*03:190, and HLA-DPA1*01:12, in an East African cohort.

Three novel human leukocyte antigen (HLA) alleles were identified using a sequence-based typing of HLA class I and class II alleles of 1867 participants from a male circumcision cohort in Kenya. The new alleles were first identified by sequencing and then confirmed by cloning the polymerase chain reaction (PCR) products and sequencing multiple clones. HLA-B*58:43 was identical to HLA-B*58:02 with the exception of a nucleotide change at codon 125 in exon 3 (GCC→ACC), and resulted in the amino acid change from Alanine to Threonine. HLA-C*03:190 was identical to HLA-C*03:02:01 with the exception of a nucleotide change at codon 131 in exon 3 (CGC→TGC), and resulted in the amino acid change from Arginine to Cysteine. HLA-DPA1*01:12 was identical to HLA-DPA1*01:03:01:01 with the exception of a nucleotide change at codon 66 in exon 2 (TTG→TCG), and resulted in the amino acid change from Leucine to Serine.

HLA class I associations with rates of HIV-1 seroconversion and disease progression in the Pumwani Sex Worker Cohort.

Class I human leukocyte antigens (HLA) play an important role in the adaptive immune response by presenting antigens to CD8+ T cells. Studies have reported that several HLA class I alleles are associated with differential disease progression in human immunodeficiency virus (HIV)-infected individuals, however, few class I associations with resistance or susceptibility to HIV-1 infection have been reported. We typed HLA-A, -B and -C of >1000 women enrolled in the Pumwani Sex Worker Cohort using a sequence-based typing method. Kaplan-Meier analysis was used to identify alleles influencing seroconversion and disease progression to acquired immune deficiency syndrome (CD4 < 200/mm³). A*01 (P = 0.020), C*06:02 (P = 0.042) and C*07:01 (P = 0.050) are independently associated with protection from seroconversion. Women with any of these alleles are less likely to seroconvert [P = 0.00001, odds ratio (OR): 0.503, 95% confidence interval (CI): 0.320-0.790]. Conversely, A*23:01 (P = 0.004), B*07:02 (P = 0.003) and B*42:01 (P = 0.025) are independently associated with rapid seroconversion. Women with any of these alleles are twice as likely to seroconvert (P = 0.002, OR: 2.059, 95% CI: 1.290-3.285). The beneficial alleles confer threefold protection from seroconversion when compared with the susceptible alleles (P = 0.000001, OR: 0.268, 95% CI: 0.132-0.544). B*07:02 is the contributing allele, within the B7 supertype, to the rapid seroconversion. A*74:01 (P = 0.04/P = 0.006), B*14 (P = 0.003/P = 0.003) and B*57:03 (P = 0.012/P = 0.038) are independently associated with slower CD4+ decline and LTNP phenotype, while B*07:02 (P = 0.020), B*15:10 (P = 0.022) and B*53:01 (P = 0.007) are independently associated with rapid CD4+ T-cell decline. B7 supertype (P = 0.00006), B*35*-Py (P = 0.028) and B*35-Px (P = 0.001) were also significantly associated with rapid CD4+ T-cell decline. Understanding why these HLA class I alleles are associated with protection/susceptibility to HIV-1 acquisition and disease progression could contribute to the development of effective prophylactic and therapeutic vaccines for HIV-1.

Identification of 23 novel MHC class I alleles in cynomolgus macaques of Philippine and Philippine/Mauritius origins.

We report here novel Mafa-A, -AG and -B alleles identified in two groups of cynomolgus macaques.

Evidence of recombination producing allelic diversity in MHC class I Mafa-B and -A alleles in cynomolgus macaques.

The MHC class I-A and -B genes of cynomolgus macaques are highly polymorphic. These genes encode proteins presenting peptides to CD8+ T cells to initiate adaptive immune response. Recombination events are one way the diversity of these alleles can be increased. Such events have been well characterized in humans, but have not been as well characterized in macaques. In order to identify and examine recombinations that create new alleles, it is important to analyze intron sequences. Intron sequences have been shown to be important to understand the evolutionary mechanisms involved in the generation of major histocompatibility complex (MHC) alleles and loci. Thus far, there have been relatively few intron sequences reported for MHC class I alleles in macaques, and this has hampered the understanding of MHC organization and evolution in macaques. In this study, we present evidence of a gene conversion event generating the Mafa-B*099 allele lineage by the combination of Mafa-B*054 and Mafa-B*095 allele lineages. A potential recombination between the Mafa-A3*13 and Mafa-A4:14 lineages was also observed, but it is less clear due to lack of intron 2 sequence. This report stresses the role that recombination can play in MHC class I diversity in cynomologus macaques, and the importance of introns in identifying and analyzing such events.

Identification of a novel HLA-A allele, A*29:28, in an East African population.

The new allele is identical to A*29:01:01:01 in exons 2 and 3, except for a single-nucleotide substitution (TTG to TGG) at codon 156.

Systems biology-based approaches to understand HIV-exposed uninfected women.

Worldwide HIV infects women more frequently than men, and it is clear that not all exposed to HIV become infected. Several populations of HIV-exposed uninfected (EU) women have been identified, including discordant couples and sex workers. Understanding what provides natural protection in EU women is critical in vaccine or microbicide development. However, correlates of protection in these women are still unclear. Most studies have used classical methods, examining single genes or cellular factors, a mainstay for traditional immunobiology. This reductionist approach may be limited in the information it can provide. Novel technologies are now available that allow us to take a "systems biology" approach, which allows the study of a complex biological system and identifies factors that may provide protection against HIV infection. Herein we report developments in discovery-based systems biology approaches in EU women and how this broadens our understanding of natural protection against HIV-1.

AIDS: an international perspective.

The acquired immunodeficiency syndrome (AIDS) and infection with the human immunodeficiency virus type 1 (HIV-1) constitute a worldwide public health problem. Whereas in Europe and in most of the Americas transmission of HIV-1 has occurred predominantly among homosexual men and intravenous drug abusers, in Africa a distinct epidemiologic pattern has emerged that indicates that HIV-1 infection is mainly heterosexually acquired. Heterosexual transmission appears to be increasing in some parts of Latin America and the Caribbean, and possibly in the United States. In addition to HIV-1, at least one other human retrovirus, namely HIV-2, has been implicated as a cause of AIDS in Africa and Europe. Factors that influence heterosexual transmission of HIV-1 include genital ulcerations, early or late stages of HIV-1 infection in the index case, and possibly oral contraception and immune activation. The rate of perinatal transmission is enhanced when the mother's illness is more advanced. AIDS and HIV-1 infection may have a significant impact not only on public health, but also on the demography and socioeconomic conditions of some developing countries. Programs for the prevention and control of AIDS should be an immediate priority in all countries.

Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection.

The severe adverse effects of gonococcal infection on human fertility suggests that Neisseria gonorrhoeae would exert powerful selection for the development of a protective immune response in humans. N. gonorrhoeae is an obligate human pathogen and must persist in humans to survive. Since it is an ecologically successful organism, it must have evolved strategies to evade any human immune response it elicits. In a longitudinal study among 243 women working as prostitutes and experiencing frequent gonococcal infection, younger women, women with HIV infection, and women with antibody to the gonococcal outer membrane protein 3 (Rmp) were at increased risk of infection (adjusted odds ratio 3.4, CI95% 1.1-10.4, P < 0.05). Rmp is highly conserved in N. gonorrhoeae and the blocking of mucosal defences may be one of its functions. As similar proteins occur in many gram negative mucosal pathogens, the enhancing effect of such proteins may be a general strategy whereby bacteria evade human immune responses.

PIP: Between March 1985 and July 1986 researchers enrolled 243 female prostitutes in Pumwani community of Nairobi, Kenya, in a longitudinal study to examine the relationship between the antibody to the gonococcal outer membrane protein 3 (Rmp Ab) and gonococcal mucosal infection. Few women used condoms. 69% were HIV-1 seropositive. Just 9.5% (23) of the women had not had any gonococcal infections, despite probable exposure to them, indicating the possibility of some acquired protective immunity to Neisseria gonorrhoea. 90.5% had had at least 1 gonococcal infection. Women with Rmp Ab faced a greater risk of gonococcal infection than those who were Rmp Ab negative (OR = 3.4;l p .05), denoting that Rmp Ab increases susceptibility to gonococcal mucosal infections. Women older than 29 years were at lower risk of gonococcal infection than those younger than 29 years (odds ratio [OR] = 0.3; p .03). Women who used oral contraceptives (OCs) were also likely to be infected with N. gonorrhoea (OR = 3; p = .062). Further, 31% of OC users had cervical ectopy compared to just 14% of nonusers (OR = 2.8; p .005), suggesting that the effect of OCs on the cervix make it more susceptible to gonococcal infection. Rmp Ab also exists in many other gram-negative mucosal pathogens, often playing the same role as it does in N. gonorrhoea infection. Thus, Rmp Ab may be a common scheme bacteria used to elude human immune responses. These findings provide more understanding as to why N. gonorrhoea is an ecologically successful human pathogen.

Epidemiologic evidence for the development of serovar-specific immunity after gonococcal infection.

We tested the hypothesis that strain-specific immunity occurs after gonococcal infection in a longitudinal study of 227 prostitutes resident in one small community who experienced frequent gonococcal infections. Women were examined and cultured for Neisseria gonorrhoeae at 2-wk intervals. Gonococcal isolates were typed according to protein 1 serovar, auxotype, and beta-lactamase plasmid type, and classified as to serovar and strain. The hypothesis was tested by comparing the predictions of the hypothesis with the observations of the study. Over the 14-mo period of the study, major changes in the prevalence of specific serovars were observed in the gonococcal population infecting these women. Women with HIV infection experienced a higher rate of gonococcal infection (0.56 +/- 0.03 vs. 0.46 +/- 0.04, P less than 0.05, t test) compared with HIV-negative women and were more likely to experience multiple infections with the same strain. The duration of prostitution was inversely related to the frequency of gonococcal infection. Women experiencing an infection with a specific gonococcal serovar were at a 2- to 10-fold reduced risk of reinfection with the same serovar, except for the 1B-1 serovar. The results of the study were consistent with all four predictions of the hypothesis. Infection with a specific gonococcal serovar results in specific but incomplete protection against subsequent infection with the homologous serovar. The mechanism of this protection remains to be determined.

Antibodies to opacity proteins (Opa) correlate with a reduced risk of gonococcal salpingitis.

Acute salpingitis complicating cervical gonococcal infection is a significant cause of infertility. Relatively little data are available concerning the pathophysiologic mechanisms of this disease. A cohort of 243 prostitutes residing in Nairobi were followed between March 1985 and April 1988. Gonococcal cultures were performed at each visit, and acute salpingitis was diagnosed clinically. Serum at enrollment was tested by immunoblot for antibody to gonococcal outer membrane proteins. 8.6% (146/1689) of gonococcal infections were complicated by salpingitis. Increased risk of salpingitis was associated with younger age, shorter duration of prostitution, HIV infection, number of gonococcal infections, and episodes of nongonococcal salpingitis. Rmp antibody increased the risk of salpingitis. Antibody to Opa decreased the risk of salpingitis. By logistic regression analysis, antibody to Opa was independently associated with decreased risk of gonococcal salpingitis (adjusted odds ratio [OR], 0.35; 95% confidence interval [95%CI], 0.17-0.76); HIV infection (adjusted OR, 3.5; 95% CI, 0.96-12.8) and episodes of nongonococcal salpingitis (adjusted OR, 3.4; 95% CI, 1.8-6.4) were independently associated with an increased risk of salpingitis. Antibody to Opa appears to protect against ascending gonococcal infection, perhaps by interfering with Opa mediated adherence and endocytosis. The demonstration of natural immunity that protects against upper genital tract infection in women suggests that a vaccine to prevent gonococcal salpingitis is possible.

Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi.

Many people who remain persistently seronegative despite frequent HIV exposure have HIV-specific immune responses. The study of these may provide information about mechanisms of natural protective immunity to HIV-1. We describe the specificity of cytotoxic T lymphocyte responses to HIV in seronegative prostitutes in Nairobi who are apparently resistant to HIV infection. These women have had frequent exposure to a range of African HIV-1 variants, primarily clades A, C, and D, for up to 12 yr without becoming infected. Nearly half of them have CTL directed towards epitopes previously defined for B clade virus, which are largely conserved in the A and D clade sequences. Stronger responses are frequently elicited using the A or D clade version of an epitope to stimulate CTL, suggesting that they were originally primed by exposure to these virus strains. CTL responses have been defined to novel epitopes presented by HLA class I molecules associated with resistance to infection in the cohort, HLA-A*6802 and HLA-B18. Estimates using a modified interferon-gamma Elispot assay indicate a circulating frequency of CTL to individual epitopes of between 1:3,200 and 1:50,000. Thus, HIV-specific immune responses-particularly cross-clade CTL activity- may be responsible for protection against persistent HIV infection in these African women.

Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses.

Resistance to HIV infection in a small group of Kenyan sex workers is associated with CD8+-lymphocyte responses to HIV cytotoxic T-lymphocyte (CTL) epitopes. Eleven prostitutes meeting criteria for HIV resistance seroconverted between 1996 and 1999. The occurrence and specificity of preexisting HIV-1 epitope-specific responses were examined using the IFN-gamma enzyme-linked immunospot assay, and any epitopes recognized were cloned and sequenced from the infecting viral isolate. Immunologic and behavioral variables were compared between late seroconverters and persistently uninfected sex worker controls. HIV-1 CTL epitope responses were present in four of six cases, 5-18 months before seroconversion, and their presence was confirmed by bulk CTL culture. A possible viral escape mutation was found in one of six epitopes. The key epidemiologic correlate of late seroconversion was a reduction in sex work over the preceding year. In persistently uninfected controls, a break from sex work was associated with a loss of HIV-specific CD8+ responses. Late seroconversion may occur in HIV-1-resistant sex workers despite preceding HIV-specific CD8+ responses. Seroconversion generally occurs in the absence of detectable CTL escape mutations and may relate to the waning of HIV-specific CD8+ responses due to reduced antigenic exposure.

CD8(+) lymphocytes respond to different HIV epitopes in seronegative and infected subjects.

HIV-1-specific cytotoxic T-lymphocyte (CTL) responses have been detected at a low frequency in many HIV-1-exposed, persistently seronegative (HEPS) subjects. However, it is unclear how CTLs could protect against HIV acquisition in HEPS subjects, when high levels of circulating CTL fail to prevent disease progression in most seropositive subjects. To address this issue we studied CD8(+) lymphocyte responses to a panel of HIV-1 CTL epitopes in 91 HEPS and 87 HIV-1-infected Nairobi sex workers. HIV-specific responses in seropositive women focused strongly on epitopes rarely or never recognized in HEPS subjects, who targeted epitopes that were subdominant or unrecognized in infected women. These differences in epitope specificity were restricted by only those HLA class I alleles that are associated with a reduced risk of HIV-1 infection in this cohort. Late seroconversion in HEPS donors was associated with a switch in epitope specificity and/or immunodominance to those epitopes preferentially recognized by HIV-1-infected women. The likelihood of detecting HIV-1-specific responses in HEPS women increased with the duration of viral exposure, suggesting that HIV-1-specific CD8(+) responses are acquired over time. The association between differential recognition of distinct CTL epitopes and protection from HIV-1 infection may have significant implications for vaccine design.

HIV pathogenesis: mechanisms of susceptibility and disease progression.

The understanding of the factors associated with HIV-1 acquisition and disease progression has been significantly advanced in the past few years. These factors can be broadly defined as intrinsic or acquired and are operative at the levels of disease acquisition and progression or both. Much recent attention has focused on the identification of allelic variants at specific genetic loci that alter either susceptibility to infection or the natural history of disease progression. In addition, a more detailed understanding of the immunologic responses to HIV-1 and factors that perturb these responses has greatly enhanced our understanding of the immunologic control of HIV-1 and the roles of cofactors in HIV-1 acquisition and disease progression.

Rapid increase of both HIV-1 infection and syphilis among pregnant women in Nairobi, Kenya.

OBJECTIVE: To determine the prevalence of HIV-1 and syphilis antibodies in a population of pregnant women in Nairobi, Kenya, between 1989 and 1991. METHODS: As part of an ongoing prospective study on the effect of HIV-1 infection and sexually transmitted diseases, 4883 pregnant women were screened for HIV-1 and syphilis antibodies in one health-centre in Nairobi. RESULTS: HIV-1 seroprevalence increased from 6.5 to 13.0% (P < 0.001) and syphilis seroreactivity from 2.9 to 5.3% (P = 0.002), while there was no change in gonococcal infection rates. The most rapid increase in HIV-1 prevalence was observed in women aged less than 25 years. There was no evidence of demographic fluctuations in the population during this time, or of changes in sexual behaviour, except that fewer women enrolled in 1991 reported having more than one sex partner, compared with women enrolled in 1989 (39.1 versus 20.0%; P = 0.0001). HIV-1-seropositive women were more likely to be seroreactive for syphilis than HIV-1-seronegative mothers (7.7 versus 3.2%; odds ratio = 2.5; 95% confidence interval, 1.7-3.8; P < 0.001), but there was no difference between the two groups in terms of gonorrhoea prevalence. CONCLUSION: These data confirm an association between HIV-1 and syphilis infection, and indicate that both are spreading rapidly among women in Nairobi outside high-risk groups. Increased efforts to control both infections are urgently required.

PIP: Between January 1989 and December 1991, health workers took blood samples from 4883 pregnant women attending the Nairobi City Commission's Langata Clinic in Nairobi, Kenya to determine demographic factors and indicators of sexual behavior to explain the increase in HIV-1 infection and syphilis among these women of low socioeconomic status. HIV-1 seroprevalence stood at 8.8%. Syphilis seroreactivity was 3.6%. HIV-1 seropositive mothers were 2.5 times more likely to also test positive for syphilis than were HIV-1 seronegative mothers (7.7% vs. 3.2%; p.001). There was no significant association between HIV-1 seropositivity and gonococcal infection rate (7.3% vs. 8.9%), however. Women who tested HIV-1 positive tended to be from western Kenya (60.1% vs. 39.1%; p.0001). Between 1989 and 1991, annual HIV-1 seroprevalence rates increased from 6.5% to 13% (p.001) as did annual syphilis seroreactivity rates (2.9-5.3%; p=.02). The HIV-1 seroprevalence rates remained high, but did not rise significantly among syphilis seroreactive women between 1989 and 1991 (17.9-20.7%). They did rise among syphilis seronegative women (6.9-12.5%; p.0001), however. The HIV-1 infection rate increase was greater among 25-year old women (5.6-13.2%; p.001) than it was among 25-year old women (6.8-12.7%; p=.09). Indeed the annual incidence rate for 25-year old women was 3-4%. Between 1989-1991, there was a decrease in the percentage of both HIV-1 seropositive and seronegative women who had had 1 sex partner during the last 2 years (39.1% vs. 20%; p=.0001). Demographic factors remained the same throughout the study period. These results verified the link between HIV-1 infection and syphilis and their rapid rise among women in low risk groups. Thus there was a pressing need to improve HIV-1 and sexually transmitted disease prevention programs.

The importance of core groups in the epidemiology and control of HIV-1 infection.

PIP: In Africa, HIV transmission occurs mainly through heterosexual intercourse. High-frequency transmitter core groups are key to the epidemiology of HIV-1 and STD on the continent. The rapid growth of the HIV-1 epidemic in Africa appears to have resulted, in part, from social and economic factors which result in individuals' frequent engagement in sexual intercourse with members of HIV-infected core groups. Understanding the importance of core groups in HIV-1 transmission is therefore key to developing more effective programs for the control of HIV-1. Sections explore the core groups concept and the sexual transmission of infection, social and economic forces creating core groups in Africa, the interaction of STD and HIV-1 in core groups, the effect of STD on HIV-1 disease progression in core groups in accelerating the HIV-1 epidemic, the role of core group interventions in control programs, balancing disease control with the potential for victimization, and research needs.^ieng

Risk factors for postnatal mother-child transmission of HIV-1.

OBJECTIVE: To identify factors affecting HIV-1 breastfeeding transmission. DESIGN: Longitudinal observational cohort study. METHODS: HIV-1 seropositive pregnant women and seronegative controls were enrolled at a maternity hospital in Nairobi. Women and their children were followed from birth, and data on HIV-1 transmission, breastfeeding, clinical illness, and growth were collected. Specimens for HIV-1 serology and/or polymerase chain reaction were obtained at birth, 2, 6, and 14 weeks, 6, 9, 12, and 18 months, and every 6 months thereafter. Children were classified as HIV-1 uninfected, perinatally, or postnatally infected. Potentially breastfeeding transmission related risk factors were compared between postnatally infected and uninfected children. RESULTS: Among children born to seropositive or seroconverting mothers, 317 were uninfected, 51 infected perinatally and 42 infected postnatally. Identified risk factors for postnatal transmission were maternal nipple lesions (OR = 2.3, CI 95% 1.1-5.0), mastitis (OR = 2.7, CI 95% 1.1-6.7), maternal CD4 cell count < 400 mm3 (OR = 4.4, CI 95% 1.9-9.9), maternal seroconversion while breastfeeding (OR = 6.0, CI 95% 1.8-19.8), infant oral thrush at < 6 months of age (OR = 2.8, CI 95% 1.3-6.2) and breastfeeding longer than 15 months (OR = 2.4, CI 95% 1.2-5.1). All factors, except maternal seroconversion due to its rarity, were independently associated with an increased postnatal transmission risk by multivariate logistic regression analysis. CONCLUSION: In addition perinatal antiretroviral therapies, public health strategies should address: (i) prevention of maternal nipple lesions, mastitis and infant thrush; (ii) reduction of breastfeeding duration by all HIV-1-infected mothers; (iii) absolute avoidance of breastfeeding by those at high risk, and (iv) prevention of HIV-1 transmission to breastfeeding mothers.

Controlling HIV in Africa: effectiveness and cost of an intervention in a high-frequency STD transmitter core group.

Since 1985, a population of over 1,000 predominantly HIV-positive female prostitutes residing in a low-income area of Nairobi, has been enrolled in a sexually transmitted disease (STD)/HIV control programme. The major elements of the programme include the diagnosis and treatment of conventional STD, and the promotion of condom use to prevent the transmission of HIV and other sexually transmitted infections. Using estimates of numbers of HIV-seropositive prostitutes, numbers of sexual contacts, susceptibility of clients to HIV, HIV transmission efficiency, rates of condom use and the basic reproductive rate of HIV infection in Kenya, we estimate that the programme is responsible for preventing between 6,000 and 10,000 new cases of HIV infection per year among clients and contacts of clients. The total annual operating cost of the programme is approximately US$77,000 or between US$8.00 and US$12.00 for each case of HIV infection prevented. Programmes to reduce the transmission of HIV and other sexually transmitted infections which are targeted at high-frequency STD transmitters, such as prostitutes, can be effective and relatively inexpensive to undertake. More such programmes should be developed and evaluated in different settings.

Stable antenatal HIV-1 seroprevalence with high population mobility and marked seroprevalence variation among sentinel sites within Nairobi, Kenya.

OBJECTIVES: To monitor and analyse trends in HIV-1 seroprevalence among antenatal women in Nairobi, Kenya. DESIGN: Six sequential surveys were carried out among antenatal clinic attenders at four Nairobi City Council health centres between November 1991 and April 1997. METHODS: A total of 6828 women attending for first antenatal clinic visit were administered a standard questionnaire to obtain demographic information and were screened for HIV-1. RESULTS: HIV-1 seroprevalence rose from 12.1% in the first survey to 16.2% in the third, completed in October 1993. No rise was observed in subsequent surveys, and seroprevalence among women under the age of 20 declined after the third survey. Significant differences in seroprevalence (P < 0.001) were observed in all survey rounds between women who reported that their province of origin was Nyanza (22.4% overall), compared with those from other provinces in western Kenya (14.1%), and the eastern group of provinces (8.9%). The rise in HIV-1 seroprevalence observed between 1991 and 1993 was almost entirely attributable to the rising seroprevalence among women from Nyanza. There were considerable differences in HIV-1 seroprevalence among the four health centres, partly accounted for by differences in the proportion of clinic attenders from different provinces of origin, which also changed significantly over time. CONCLUSIONS: HIV-1 seroprevalence has stabilized in antenatal women attending these health centres in Nairobi, and may be declining among women in the youngest age group. This may reflect stabilization of HIV-1 incidence, but further observation is required. The levels of infection among Nairobi residents reflect the evolution of the HIV epidemic in their provinces of origin, and changing client composition influences HIV-1 seroprevalence at different clinics. HIV sentinel surveillance should be carried out at multiple sites in large urban centres to monitor accurately the evolution of the HIV epidemic and the impact of control efforts in reducing transmission.

Increased interleukin-10 in the the endocervical secretions of women with non-ulcerative sexually transmitted diseases: a mechanism for enhanced HIV-1 transmission?

OBJECTIVE: Although non-ulcerative sexually transmitted diseases (STD) and bacterial vaginosis are implicated as cofactors in heterosexual HIV-1 transmission, the mechanisms have not been defined. Recent in vitro data suggest that interleukin (IL)-10 may increase susceptibility of macrophages to HIV-1 infection. Therefore, we performed this study to assess whether non-ulcerative STD are associated with detection of IL-10 in the female genital tract. METHODS: Women with clinical pelvic inflammatory disease with or without cervicovaginal discharge were recruited from an STD clinic in Nairobi, Kenya. Endocervical and endometrial specimens were obtained for Neisseria gonorrhoeae and Chlamydia trachomatis DNA detection, Trichonomas vaginalis culture, and CD4 and CD8 T-cell enumeration. Bacterial vaginosis was diagnosed by Gram stain. IL-10 was detected in endocervical specimens using enzyme-linked immunosorbent assay. Blood was obtained for HIV-1 serology. RESULTS: One hundred and seventy-two women were studied. N. gonorrhoeae, C. trachomatis, bacterial vaginosis, and T. vaginalis were detected in 38 (21%), 17 (9%), 71 (43%), and 22 (12%) women, respectively. Cervical IL-10 was detected more often in women with N. gonorrhoeae [adjusted odds ratio (AOR), 3.4; 95% confidence interval (CI), 1.4-8.4], C. trachomatis (AOR, 4.4; 95% CI, 1.2-15.6), and bacterial vaginosis (AOR, 3.1; 95% CI, 1.4-6.9) than in women without these infections. CONCLUSIONS: The association of non-ulcerative STD and bacterial vaginosis with increased frequency of IL-10 detection in endocervical secretions suggests a potential mechanism through which these infections may alter susceptibility to HIV-1 infection in women.