Serologic testing algorithm for recent HIV seroconversion in estimating incidence of HIV-1 among adults visiting a VCT centre at a Kenyan tertiary health institution.

OBJECTIVE: To determine HIV high risk groups among adults visiting Kenyatta National Hospital Voluntary Counselling and Testing Centre by use of Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS). DESIGN: A cross-sectional study of adults. SETTING: Kenyatta National Hospital Voluntary and Counselling Centre. RESULTS: Of the 6,415 adults screened for antibodies to HIV at Kenyatta National Hospital VCT Centre between July 2002 and February 2003, 728 tested positive in the two HIV screening tests used at the center, indicating a prevalence of 11%. Of these seropositive cases, 355 consented to participate in the study. Using STARHS, 34 (9.6%) of the plasma samples were classified as being from individuals with recent infection (within 170 days), giving an annual estimated HIV-1 incidence in this population of 1.3 infections per 100 person-years with a 95% CI of 0.872-1.728%. Young adults had a higher rate of new infection than older adults. Young females were infected much earlier in life, with a peak age of new infections of 26 years, versus 31 years for young males. CONCLUSION: This study confirms our hypothesis that STARHS or Detuned assay can be used to determine HIV incidence in this population. The HIV high risk groups as identified by this study are young women between ages 16 to 26 years old and men between ages 45 to 55 years of age.

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.

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.

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.

Human immunodeficiency virus infection in long-distance truck drivers in east Africa.

BACKGROUND: A cross-sectional survey was performed to determine the seroprevalence and correlates of human immunodeficiency virus (HIV) infection among long-distance truck drivers in Kenya. METHODS: Truck drivers along the Mombasa-Nairobi highway were enrolled at a roadside research clinic. A standardized interview and serologic evaluation for HIV and syphilis were conducted. RESULTS: We enrolled 970 truck drivers and their assistants of whom 257 (27%) had HIV antibodies. In univariate analysis, HIV infection was correlated with older age, non-Kenyan nationality, Christian religion, longer duration of truck driving, travel outside of Kenya, less frequent visits to wives, and more frequent visits to prostitutes. Uncircumcised status, history of genital ulcer disease or urethritis during the previous 5 years, and a positive Treponema pallidum hemagglutination assay for syphilis were each associated with positive HIV serostatus. Univariate correlates of uncircumcised status included younger age, non-Kenyan nationality, Christian religion, travel outside of Kenya, and less frequent visits to prostitutes. There was a significant association between uncircumcised status and 5-year history of genital ulcer disease or serologic evidence of syphilis, but not with 5-year history of urethritis. In multivariate analysis, HIV infection was independently associated with uncircumcised status (adjusted odds ratio [OR], 4.9; 95% confidence interval [CI], 2.8 to 8.4), history of genital ulcer disease (adjusted OR, 2.4; 95% CI, 1.5 to 4.1), history of urethritis (adjusted OR, 1.8; 95% CI, 1.1 to 2.9), more frequent sex with prostitutes (more than once per month; adjusted OR, 1.7; 95% CI, 1.1 to 2.8), and positive T pallidum hemagglutination assay (adjusted OR, 1.2; 95% CI, 1.0 to 1.4). The attributable risk percentage for the association between HIV and uncircumcised status was 70%, and the population attributable risk was 25%. CONCLUSIONS: Truck drivers in east Africa are at high risk of HIV infection. The strongest correlates of HIV seropositivity were uncircumcised status and history of both ulcerative and nonulcerative sexually transmitted diseases.

Comparison of pap smear, visual inspection with acetic acid, human papillomavirus DNA-PCR testing and cervicography.

OBJECTIVE: To assess the test qualities of four screening methods to detect cervical intra-epithelial neoplasia in an urban African setting. METHOD: Six hundred fifty-three women, attending a family planning clinic in Nairobi (Kenya), underwent four concurrent screening methods: pap smear, visual inspection with acetic acid (VIA), PCR for high risk human papillomavirus (HR HPV) and cervicography. The presence of cervical intra-epithelial neoplasia (CIN) was verified by colposcopy or biopsy. RESULT: Sensitivity (for CIN2 or higher) and specificity (to exclude any CIN or cancer) were 83.3% (95% CI [73.6, 93.0]) and 94.6% (95% CI [92.6, 96.5]), respectively, for pap smear; 73.3% (95% CI [61.8, 84.9]) and 80.0% (95% CI [76.6, 83.4]) for VIA; 94.4% (95% CI [84.6, 98.8]) and 73.9% (95% CI [69.7, 78.2]) for HR HPV; and 72.3% (95% CI [59.1, 85.6]) and 93.2% (95% CI [90.8, 95.7]) for cervicography. CONCLUSION: The pap smear had the highest specificity (94.6%) and HPV testing the highest sensitivity (94.4%). The visual methods, VIA and cervicography, were similar and showed an accuracy in between the former two tests.

HIV-1 and immunological changes during pregnancy: a comparison between HIV-1-seropositive and HIV-1-seronegative women in Nairobi, Kenya.

OBJECTIVE: To assess changes in the proportion of CD4 and CD8 T-lymphocyte profiles during pregnancy, at delivery and postpartum, and to determine whether HIV-1 infection affects the normal profile. DESIGN AND METHODS: A total of 416 pregnant HIV-1-infected women and an age and parity-matched HIV-seronegative group of 407 pregnant women were enrolled into a prospective study on the impact of HIV-1 infection on pregnancy. Maternal blood was obtained for lymphocyte subset determination at enrollment, delivery and 6 weeks postpartum. Whole blood sample drawn in EDTA-containing tubes were used to determine T-helper/inducer (CD4) and T-suppressor/cytotoxic (CD8) cells by direct immunofluorescence using monoclonal antibodies. RESULTS: No relationship was found between gestational age and any immunological variable. The CD4 percentage was lower postpartum than antenatally, in both HIV-1-seropositive and seronegative women, but this was not true for absolute CD4 counts. CD8 absolute counts and percentages were significantly higher postpartum than antenatally. The differences between HIV-1-seropositive and seronegative women in changes over pregnancy in CD4 and CD8 cells and their ratio, were not statistically significant. CONCLUSION: Our findings do not support a short-term synergistic effect of HIV-1 and pregnancy on the immune function as determined by T-lymphocyte subsets.

PIP: The impact of HIV-1 on pregnancy was investigated in a prospective case-control study of 416 pregnant HIV-infected women and 407 age- and parity-matched pregnant HIV-seronegative women from Nairobi, Kenya. No relationship existed between gestational age (14-30 weeks) and any hematologic or immunologic variable studied. In both cases and controls, the CD4 percentage (but not absolute count) was lower postpartum than during pregnancy, while CD8 absolute counts and percentages were significantly higher in the postpartum period. The differences between HIV-positive and HIV-negative women in changes during pregnancy in CD4 and CD8 cells and their ratio were not statistically significant. These findings fail to provide support for a synergistic effect of HIV-1 and pregnancy on immune function. Further studies are needed, however, to assess the long-term effects of pregnancy in HIV-infected women, to determine the impact of pregnancy at different stages of HIV disease, and to establish normal and HIV-1-related T-lymphocyte subset profiles during the entire course of pregnancy in African women.

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

Acceptability of HIV vaccine trials in high-risk heterosexual cohorts in Mombasa, Kenya.

OBJECTIVES: To ascertain the level of acceptance of a prophylactic HIV vaccine trial in high-risk HIV-seronegative heterosexual cohorts of men and women in Mombasa, Kenya, and to assess the anticipated effects of participation on risk behavior. METHODS: Standardized questionnaire administered to a convenience sample of commercial sex workers and trucking company employees enrolled in prospective cohort studies. RESULTS: Ninety-six per cent of respondents believed that HIV was a major problem in Kenya and 86% of men and 94% of women perceived themselves at risk. One hundred per cent of women and 84% of men expressed interest in participation in an HIV vaccine trial, after explanation of the experimental nature of the vaccine, double-blind placebo-controlled design, prolonged follow-up and potential change in serostatus. Seventeen per cent of men and 9% of women anticipated an increase in risk behavior as a result of participation. CONCLUSION: The majority of individuals in two high-risk cohorts were interested in participating in Phase III efficacy trials of HIV vaccines. A significant minority anticipated an increase in risk behavior, which emphasizes the need for intensive counseling and education throughout a vaccine trial.

PIP: The acceptability of a theoretical human immunodeficiency virus (HIV) vaccine trial was investigated in HIV-negative commercial sex workers and trucking company employees in Mombasa, Kenya. The 206 women and 201 men who completed questionnaires were already enrolled in a prospective cohort study of high-risk heterosexuals. 95% of men and 98% of women surveyed agreed that acquired immunodeficiency syndrome (AIDS) is a major problem in Kenya; however, only 14% and 6%, respectively, considered themselves at personal risk of infection. Only 4% of male and 1% of female respondents stated they would refuse an HIV vaccine of proven safety and efficacy. However, 91% of women but only 67% of men indicated they would participate in a double-blind, placebo-controlled vaccine trial that involved vaccine-induced HIV seropositivity and prolonged follow-up. The main concerns about participation in such a trial were the positive HIV blood test result and fear of acquiring HIV from the vaccine. 9% of men and 6% of women anticipated they would decrease their condom use as a result of participation in such a trial, and 9% of men and 3% of women thought they would increase their number of sexual partners. Anticipated higher risk behavior was significantly associated with male gender, but not with age, education, history of prostitution or of sex with prostitutes, or current condom use. If and when vaccine trials become possible, this high-risk cohort would comprise an ideal target population; however, concurrent counseling about the need to continue preventive behavioral measures would be a necessity.

Female condom introduction and sexually transmitted infection prevalence: results of a community intervention trial in Kenya.

OBJECTIVE: To measure the impact on sexually transmitted infection (STI) prevalence of a female condom introduction and risk-reduction program at Kenyan agricultural sites. DESIGN: We conducted a cluster-randomized trial to determine whether a replicable, community-level intervention would reduce STI prevalence. METHODS: Six matched pairs of tea, coffee and flower plantations were identified. The six intervention sites received an information/motivation program with free distribution of female and male condoms, and six control sites received only male condoms and related information. Participants were tested for cervical gonorrhea and chlamydia by ligase chain reaction on urine specimens, and vaginal trichomoniasis by culture, at baseline, 6 and 12 months. RESULTS: Participants at intervention (n = 969) and control sites (n = 960) were similar; baseline STI prevalence was 23.9%. Consistent male condom use was more than 20% at 12 months. Consistent female condom use was reported by 11 and 7% of intervention site women at 6 and 12 months. Unadjusted STI prevalence was 16.5 and 17.4% at 6 months, and 18.3 and 18.5% at 12 months, at the intervention and control sites, respectively. Logistic regression models confirmed the null effect of the female condom intervention. CONCLUSIONS: Female condom introduction did not enhance STI prevention at these sites. It is unclear which aspects of the intervention -- STI education, condom promotion, case management -- were associated with decreased STI prevalence from baseline to follow-up.

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.

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.

Cofactors for the acquisition of HIV-1 among heterosexual men: prospective cohort study of trucking company workers in Kenya.

OBJECTIVE: To determine the prevalence, incidence, and correlates of HIV-1 infection in a cohort of east African trucking company employees. METHODS: HIV-1-seronegative trucking company employees were enrolled in a prospective cohort study and evaluated at 3 monthly intervals for HIV-1 seroconversion, sexually transmitted diseases, and sexual behavior. RESULTS: The baseline seroprevalence of HIV-1 among 1500 trucking company employees was 17.8%. Among 752 HIV-1-seronegative men who were followed, the HIV-1 annual seroincidence was 3.1%. In univariate analysis, HIV-1 acquisition was associated with age under 25 years, 10 years or less of sexual activity, occupation as a driver/driver's assistant, occupational travel for more than 14 days per month, religion other than Christian or Muslim, uncircumcised status, sex with a prostitute, sex with a girlfriend/casual partner, extramarital sex, and enrollment seropositivity to Treponema pallidum, Haemophilus ducreyi, and Herpes simplex virus type 2 (all P values < or = 0.05). Using multivariate analysis, HIV-1 acquisition was independently associated with 10 years or less of sexual activity (hazard rate ratio (HRR) 2.0, 95% confidence interval (CI) 1.0-4.3), occupation as a driver/driver's assistant (HRR 3.9, 95% CI 1.7-9.0), religion other than Christian or Muslim (HRR 6.1, 95% CI 1.4-25.7), uncircumcised status (HRR 2.3, 95% CI 1.0-5.0), and unprotected sex with a prostitute (HRR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Trucking company employees had a high HIV-1 seroprevalence rate at enrollment and a high HIV-1 seroincidence during follow-up. Risk factors for HIV-1 seroconversion included years of sexual activity, occupation, religion, uncircumcised status, and unprotected sex with a prostitute. This population is an appropriate target for HIV-1 prevention trials and behavioral interventions.

Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate.

OBJECTIVE: To characterize functional properties of HIV-specific IgA in samples representing both systemic and mucosal compartments of HIV-1 highly exposed persistently seronegative (HEPS) individuals. METHODS: IgA was purified from plasma and mucosal samples from HEPS individuals and tested for the ability to neutralize infection of peripheral blood mononuclear cells (PBMC) by a non-syncytium inducing HIV-1 (clade B) primary isolate. None of these individuals had measurable HIV-1-specific IgG. RESULTS: HIV-1-specific neutralizing activity of the purified IgA from plasma (n = 15), saliva (n = 15) and cervicovaginal fluid (CVF) (n = 14) were found in the majority of samples (73, 73 and 79%, respectively). In contrast, plasma, saliva and CVF samples of low-risk, uninfected HIV-seronegative individuals lacked neutralizing IgA, with the exception of two out of 34 (6%) saliva samples. CONCLUSION: Mucosal and plasma IgA from HEPS individuals can neutralize HIV-1 infection.

Exposure to HIV-1 during delivery and mother-to-child transmission.

BACKGROUND: The correlation between the presence of HIV-1 in maternal cervicovaginal secretions and in the infant's oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism. METHODS: Women without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery. RESULTS: Between April 1998 and April 1999, 228 woman-infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oropharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0-2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5-7.3) and of HIV-1 DNA in oro-pharyngeal secretions (adjusted OR, 3.2; 95% CI, 1.1-9.0). DISCUSSION: As far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infant's oropharyngeal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route.

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.

Decreased incidence of sexually transmitted diseases among trucking company workers in Kenya: results of a behavioural risk-reduction programme.

OBJECTIVE: To establish a cohort of high-risk individuals suitable for HIV-prevention trials, and to measure changes in sexual behaviour and sexually transmitted disease (STD) incidence after a behavioural intervention. DESIGN: Prospective cohort study in trucking company depots in Mombasa, Kenya. PARTICIPANTS: A total of 556 male HIV-seronegative employees of trucking companies. INTERVENTIONS: HIV serological testing, individual counselling, condom promotion, STD diagnosis and management. MAIN OUTCOME MEASURES: Sexual risk behaviour and symptomatic STD incidence. RESULTS: Using time-trend modelling, significant declines in self-reported high-risk sexual behaviour were demonstrated during a 1-year follow-up. The percentage of men reporting any extramarital sex during the 3-month period prior to a follow-up visit decreased from 49% durig the first quarter of follow-up to 36% during the last quarter (P < 0.001). The decline in reported female sex worker contact was from 12% to 6% (P = 0.001). Approximately 30% of men reported consistent condom use during extramarital sex and this percentage remained unchanged during the study period. The incidence of STD declined from 34 per 100 person years (PY) during the first quarter to 10 per 100 PY during the last quarter (P = 0.001). Significant reductions in gonorrhoea (15 to five cases per 100 PY, P = 0.04), non-gonococcal urethritis (10 to two cases per 100 PY, P = 0.05), and genital ulcer disease (nine to two cases per 100 PY, P = 0.02) were observed. CONCLUSIONS: Among truck company workers who participated in a cohort study in Mombasa, Kenya, there was a significant decrease in sex with high-risk partners, but no change in condom use. The change in heterosexual risk behaviour was accompanied by a significant decrease in incidence of gonorrhoea, non-gonococcal urethritis, and genital ulcer disease.

PIP: 556 male HIV-seronegative male employees of trucking companies in Mombasa, Kenya, were exposed to HIV serological testing, individual counseling, condom promotion, and sexually transmitted disease (STD) diagnosis and management, and returned for at least one follow-up visit in a prospective study to measure changes in sexual behavior and STD incidence after the intervention. There was a significant decrease in sex with high-risk partners over the 1-year period of follow-up, but no change in condom use among study participants; 30% of men reported consistent condom use during extramarital sex throughout the study period. The change in heterosexual risk behavior was accompanied by a significant decrease in the incidence of gonorrhea, nongonococcal urethritis, and genital ulcer disease. The percentage of men reporting extramarital sex decreased from 49% to 36%, while contact with female prostitutes declined from 12% to 6%.

Recent transmission of tuberculosis in a cohort of HIV-1-infected female sex workers in Nairobi, Kenya.

OBJECTIVES: To describe the epidemiological and clinical characteristics of HIV-related tuberculosis in a female cohort, and to investigate the relative importance of recently transmitted infection and reactivation in the pathogenesis of adult HIV-related tuberculosis. DESIGN: Members of an established cohort of female sex workers in Nairobi were enrolled in a prospective study. Women were followed up regularly and seen on demand when sick. METHODS: Between October 1989 and September 1992 we followed 587 HIV-infected and 132 HIV-seronegative women. Standard protocols were used to investigate common presentations. Cases of tuberculosis were identified clinically or by culture. All available Mycobacterium tuberculosis strains underwent DNA fingerprint analysis. RESULTS: Forty-nine incident and four recurrent episodes of tuberculosis were seen in HIV-infected women; no disease was seen in seronegative sex workers (P = 0.0003). The overall incidence rate of tuberculosis was 34.5 per 1000 person-years amongst HIV-infected participants. In purified protein derivative (PPD) skin test-positive women the rate was 66.7 per 1000 person-years versus 18.1 per 1000 person-years in PPD-negative women. Twenty incident cases (41%) were clinically compatible with primary disease. DNA fingerprint analysis of strains from 32 incident cases identified two clusters comprising two and nine patients; allowing for index cases, 10 patients (28%) may have had recently transmitted disease. Three out of 10 (30%) patients who were initially PPD skin test-negative became PPD-positive. Taken together, 26 incident cases (53%) may have been recently infected. DNA fingerprint analysis also identified two (50%) of the four recurrent tuberculosis episodes as reinfection. CONCLUSIONS: Substantial recent transmission of tuberculosis appears to be occurring in Nairobi amongst HIV-infected sex workers. It may be incorrect to assume in other regions of high tuberculosis transmission that active HIV-related tuberculosis usually represents reactivation of latent infection.

PIP: A 3-year (1989-92) prospective study of 587 HIV-positive and 132 HIV-negative commercial sex workers in Nairobi, Kenya, revealed substantial recent transmission of tuberculosis in the HIV-infected group. The cohort was enrolled at a community clinic that provides counseling, sexually transmitted disease services, and free condoms. In HIV-positive women, 49 incident and 4 recurrent episodes of tuberculosis were diagnosed during the study period; there were no tuberculosis cases among HIV-negative women. The overall incidence rate of tuberculosis was 34.5/1000 person-years among HIV-positive women. 20 incident cases (41%) met the clinical case definition of primary disease. DNA fingerprint analysis of strains from 32 incident cases suggested 10 women (28%) may have had recently transmitted disease. 3 of 10 women who were initially purified protein derivative (PPD) skin test-negative became PPD-positive. Clinical presentation, tuberculin skin testing, and strain clustering data all independently suggested that substantial Mycobacterium tuberculosis transmission was occurring in HIV-infected prostitutes during the study period. As many as 26 (53%) of the 49 patients with incident disease may have recently acquired tuberculosis and DNA fingerprint analysis identified 2 (50%) of the 4 recurrent tuberculosis episodes as reinfection. These findings challenge the assumption that tuberculosis in HIV-infected individuals represents reactivation of latent endogenous infection.

Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers.

BACKGROUND: Vitamin A is involved in normal immune function and the maintenance of mucosal integrity through complex effects on cellular differentiation. OBJECTIVE: We sought to determine whether serum vitamin A levels were associated with altered susceptibility to primary infection with HIV-1 in men with high-risk sexual behaviour and genital ulcers who presented for treatment at an STD clinic in Nairobi, Kenya. METHODS: HIV-1 seronegative men were prospectively followed. Vitamin A levels at study entry were compared among 38 men who HIV-1 seroconverted versus 94 controls who remained HIV seronegative. RESULTS: Vitamin A deficiency (retinol less than 20 microg/dl) was very common and was present in 50% of HIV-1 seroconverters versus 76% of persistent seronegatives. Seroconversion was independently associated with a retinol level greater than 20 microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04). Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23-0.93, P = 0.03). CONCLUSION: Vitamin A deficiency was not associated with an increased risk of HIV-1 infection among men with concurrent STD. A decreased risk of HIV-1 seroconversion was independently associated with lower retinol levels. The effects of vitamin A on macrophage and lymphoid cell differentiation may paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable individuals, such as men with genital ulcers. Lack of circumcision and chancroid are confirmed as important co-factors for heterosexual HIV-1 transmission. The role of vitamin A in heterosexual HIV-1 transmission requires further study.

Treatment of cervicitis is associated with decreased cervical shedding of HIV-1.

OBJECTIVE: To determine whether cervical mucosal shedding of HIV-1 RNA and HIV-1 infected cells decreases following successful treatment of cervicitis. DESIGN: Prospective interventional study. SETTING: Sexually Transmitted Infections Clinic, Coast Provincial General Hospital, Mombasa, Kenya. PARTICIPANTS: Thirty-six HIV-1 seropositive women with cervicitis: 16 with Neisseria gonorrhoeae, seven with Chlamydia trachomatis, and 13 with non-specific cervicitis. INTERVENTIONS: Treatment of cervicitis. MAIN OUTCOME MEASURES: Levels of total (cell-free and cell-associated) HIV-1 RNA and presence of HIV-1 DNA (a marker for infected cells) in cervical secretions before and after resolution of cervicitis. RESULTS: After treatment of cervicitis, the median HIV-1 RNA concentration in cervical secretions was reduced from 4.05 to 3.24 log10 copies/swab (P = 0.001). Significant decreases in cervical HIV-1 RNA occurred in the subgroups with N. gonorrhoeae (3.94 to 3.28 log10 copies/swab; P = 0.02) and C. trachomatis (4.21 to 3.19 log10 copies/swab; P = 0.02). Overall, the prevalence of HIV-1 infected cells in cervical secretions also decreased after treatment, from 67% to 42% (odds ratio, 2.8; 95% confidence interval, 1.3-6.0; P = 0.009). Detection of infected cells was associated with higher mean HIV-1 RNA levels (4.04 versus 2.99 log10 copies/swab; P< 0.0001). CONCLUSIONS: Effective treatment of cervicitis resulted in significant decreases in shedding of HIV-1 virus and infected cells in cervical secretions. Treatment of sexually transmitted diseases may be an important means of decreasing the infectivity of HIV-1 seropositive women by reducing exposure to HIV-1 in genital secretions.