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.

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.

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.

Transition dynamics of HIV disease in a cohort of African prostitutes: a Markov model approach.

The progression of HIV-related disease from infection to death is represented as a staged Markov model. Transitions between stages are considered reversible. The model is fitted to data from a cohort of African prostitutes by means of maximum likelihood. It appears that the progression to symptomatic disease (Centers for Disease Control stage IV) in this population is considerably more rapid than that reported from studies in Western countries.

PIP: Identifying the incubation period of HIV infection is important for individual prognoses, for developing and testing intervention strategies, for determining the reproductive rate of the disease, and for prevalence of the disease. Mathematical modeling of HIV infection in Africa is necessitated because the disease is more widespread and the immune system is constantly active due to the exposure to diseases such as malaria and tuberculosis. The Markov model for this analysis was selected because parametric estimation is not based on the time a stage is entered, but on the duration between observations and the stages at the time of observation. The HIV infected female prostitutes in the Pumwani area of Nairobi, Kenya (a population primarily of Tanzanian origin) have been identified as a study population since 1985, and seen every 6 months in clinic, or as needed. Data are constricted by the movement out of the area in the end stage of disease, which is only partially solved by tracking with community health workers. The stages identified in incubation estimation are stage 1: seropositive but symptom free (CDC stage II); stage 2: generalized lymphadenopathy (CDC stage III); stage 3: symptomatic disease (CDC stage IV); and stage 4: death. Data reflect the movement back and forth between stage 1 and 2, between 2 and 3, so the model is not a pure Longini model but rather a timed homogeneous staged model with reversible stages called transition parameters computed in a numerical differentiation. The Fortran computer program for the analyses is available from the authors. The results suggest a quick transition between seroconversion and lymphadenopathy (2.4 months) and unlikely reversal, with the mean waiting time until passage to stage 3 is approximately 2.6 years and conversions are common. Since opportunistic infections are treatable, this makes sense. Assuming a correct model, the estimation of the transition time of 20 months of h34 value of .01 and .05, the mean passage time from stage 1, 2, 3 to 4 (death) is 9.1, 8.9, and 6.2 years 12.9, 12.7, and 10.1 years respectively. The implications are that 1) when infectiousness is hypothesized to be not uniform, peak infectivity occurs earlier in Africa than in the West at least among prostitutes, or 2) if infectivity is constant throughout the incubation period, then HIV transmission must be higher in Africa to explain the high rate of infection.

HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan sex workers.

OBJECTIVES: Most HIV-1 transmission is sexual; therefore, immune responses in the genital mucosa may be important in mediating protection against HIV infection. This study examined HIV-1-specific mucosal IgA in a cohort of HIV-1-resistant Kenyan female sex workers. METHODS: HIV-1-specific immune responses were compared in HIV-1-resistant and HIV-1-infected sex workers, and in lower risk uninfected women. Cervical and vaginal samples from each group were tested for HIV-1-specific IgA and IgG by enzyme immunoassay. Systemic T-helper lymphocyte cell responses to HIV-1 envelope peptide epitopes were assayed using an interleukin 2 bioassay. HIV-1 risk-taking behaviours were assessed using standardized questionnaires. RESULTS: HIV-1-specific IgA was present in the genital tract of 16 out of 21 (76%) HIV-1-resistant sex workers, five out of 19 (26%) infected women, and three out of 28 (11%) lower risk women (P < 0.0001). Among lower risk women, the presence of HIV-1-specific IgA was associated with HIV-1 risk-taking behaviour. Systemic T-helper lymphocyte responses to HIV-1 envelope peptides were present in 11 out of 20 (55%) HIV-1-resistant women, four out of 18 (22%) infected women, and one out of 25 (4%) lower risk women (P < 0.001). T-helper lymphocyte responses did not correlate with the presence or titre of virus-specific mucosal IgA in any study group. CONCLUSIONS: HIV-1-specific IgA is present in the genital tract of most HIV-1-resistant Kenyan sex workers, and of a minority of lower risk uninfected women, where it is associated with risk-taking behaviour. These data suggest a role for mucosal HIV-1-specific IgA responses in HIV-1 resistance, independent of host cellular responses.

HIV infection among lower socioeconomic strata prostitutes in Nairobi.

A cohort of 418 lower socioeconomic strata prostitutes were enrolled in a study of the epidemiology of sexually transmitted diseases (STDs) between January and April 1985. Sixty-two per cent of the women were seropositive for HIV infection at enrollment. Significant associations were found between HIV seropositivity and Tanzanian origin (OR = 2.12, CI 95% = 1.18-3.81, P less than 0.03), younger age, a shorter duration of prostitution, reduced fecundity, use of oral contraceptives (OR = 1.8, CI 95% = 1.1-2.9, P less than 0.05) and genital ulcer disease (OR = 3.32, P less than 0.00001). No associations were noted with other STD. Stepwise logistic regression analysis confirmed independent associations between HIV infection and Tanzanian origin (OR = 2.27, CI 95% = 1.25-4.14, P less than 0.007), reduced fecundity (OR = 0.83, CI 95% = 0.74-0.94, P less than 0.003), oral contraceptive use (OR = 2.02, CI 95% = 1.22-3.35, P less than 0.006) and duration of prostitution (OR = 0.39, CI 95% = 0.23-0.65, P less than 0.004). Oral contraceptives may increase susceptibility to HIV or may be a marker for other factors which increase risk of acquisition. Further studies are necessary to confirm this association.

Isoniazid preventive therapy for tuberculosis in HIV-1-infected adults: results of a randomized controlled trial.

OBJECTIVES: To determine the efficacy of isoniazid 300 mg daily for 6 months in the prevention of tuberculosis in HIV-1-infected adults and to determine whether tuberculosis preventive therapy prolongs survival in HIV-1-infected adults. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial in Nairobi, Kenya. SUBJECTS: Six hundred and eighty-four HIV-1-infected adults. MAIN OUTCOME MEASURES: Development of tuberculosis and death. RESULTS: Three hundred and forty-two subjects received isoniazid and 342 received placebo. The median CD4 lymphocyte counts at enrolment were 322 and 346 x 10(6)/l in the isoniazid and placebo groups, respectively. The overall median follow-up from enrolment was 1.83 years (range, 0-3.4 years). The incidence of tuberculosis in the isoniazid group was 4.29 per 100 person-years (PY) of observation [95% confidence interval (CI) 2.78-6.33] and 3.86 per 100 PY of observation (95% CI, 2.45-5.79) in the placebo group, giving an adjusted rate ratio for isoniazid versus placebo of 0.92 (95% CI, 0.49-1.71). The adjusted rate ratio for tuberculosis for isoniazid versus placebo for tuberculin skin test (TST)-positive subjects was 0.60 (95% CI, 0.23-1.60) and for the TST-negative subjects, 1.23 (95% CI, 0.55-2.76). The overall adjusted mortality rate ratio for isoniazid versus placebo was 1.18 (95% CI, 0.79-1.75). Stratifying by TST reactivity gave an adjusted mortality rate ratio in those who were TST-positive of 0.33 (95% CI, 0.09-1.23) and for TST-negative subjects, 1.39 (95% CI, 0.90-2.12). CONCLUSIONS: Overall there was no statistically significant protective effect of daily isoniazid for 6 months in the prevention of tuberculosis. In the TST-positive subjects, where reactivation is likely to be the more important pathogenetic mechanism, there was some protection and some reduction in mortality, although this was not statistically significant. The small number of individuals in this subgroup made the power to detect a statistically significant difference in this subgroup low. Other influences that may have diluted the efficacy of isoniazid include a high rate of transmission of new infection and rapid progression to disease or insufficient duration of isoniazid in subjects with relatively advanced immunosuppression. The rate of drug resistance observed in subjects who received isoniazid and subsequently developed tuberculosis was low.

Health outreach and control of HIV infection in Kenya.

This paper highlights the role of mobilization of individuals and community groups and health professionals in prevention of HIV transmission. It traces the educational strategy employed to reach the general population and selected groups at risk. In Kenya, the general awareness about AIDS started to grow in late 1985 and increased in 1986-87. This has resulted in reduction of the incidence of some sexually transmitted diseases (STDs). The importance of pretesting education material as well as monitoring and evaluation of educational efforts to lay the ground for culturally appropriate and more effective health education messages to combat HIV transmission is presented. The paper concludes by emphasizing the importance of developing the HIV infection programs with the people and for the people.

Sexual behaviour in Kenya: implications for sexually transmitted disease transmission and control.

Sexual behaviour in Kenya in relation to STD transmission was investigated with a view to forming a basis for the more rational design of STD/HIV control interventions. Questionnaires were administered to a sample of 762 men and women attending eight health facilities in two urban centres. Equal numbers of STD patients (cases) and non-STD related clinic attenders (clinic controls) were selected, matched by gender and clinic. Another sample of 427 men and women was obtained from a random sampling of households in a slum area in Nairobi (community controls). Male STD patients who were unmarried, or married but living apart from their wives, reported a higher mean number of sex partners in the previous three months than did male clinic or community controls. Unmarried female STD patients reported a higher mean number of sex partners in the previous three months than did unmarried female clinic or community controls. Both male and female STD patients were more likely to report having been involved in commercial sex transactions in the previous three months than clinic or community controls. Considerable heterogeneity in sexual behaviour was apparent. In multivariate analysis, the most important predictor of STD acquisition for both men and women was the number of reported sex partners in the previous three months. In addition, for men only, marital status (unmarried, or married but living apart from their wives) and purchasing sex were significant predictors of being an STD patient. These data confirm the importance of commercial sex in STD transmission, and suggest that men play a bridging role between female sex workers and the general population of women.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized, placebo-controlled trial of monthly azithromycin prophylaxis to prevent sexually transmitted infections and HIV-1 in Kenyan sex workers: study design and baseline findings.

Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections (STIs) and HIV-1 in a cohort of Nairobi female sex workers (FSWs). A questionnaire was administered and a medical examination was performed. HIV-negative women were randomly assigned to either one gram azithromycin or placebo monthly. Mean age of the 318 women was 32 years, mean duration of sex work 7 years and mean number of clients was 4 per day. High-risk behaviour was frequent: 14% practised anal intercourse, 23% sex during menses, and 3% used intravenous drugs. While 20% reported condom use with all clients, 37% never use condoms. However, STI prevalence was relatively low: HIV-1 27%, bacterial vaginosis 46%, Trichomonas vaginalis 13%, Neisseria gonorrhoeae 8%, Chlamydia trachomatis 7%, syphilis 6% and cervical intraepithelial neoplasia (CIN) 3%. It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes, including a proposed trial of HIV prevention through STI chemoprophylaxis.

Focused peer-mediated educational programs among female sex workers to reduce sexually transmitted disease and human immunodeficiency virus transmission in Kenya and Zimbabwe.

Peer-mediated education programs in Kenya and Zimbabwe focusing on female sex workers for the control of human immunodeficiency virus (HIV) infection and other sexually transmitted diseases (STDs) have led to increased condom use and increased adoption of other safer sex practices, as well as declines in STD and HIV incidence among female sex workers. It is likely that similar declines have occurred among their clients and possibly in the general community, although supporting data are limited. These results are encouraging. However, progress in increasing the scale and coverage of intervention programs among female sex workers has been slow. Constraints to expanding program coverage include inadequate political commitment; deficiencies in program planning, management, and human resources; and insufficient funding. The challenges currently are to show that behavioral change can be sustained and to scale up activities from small demonstration projects to district, provincial, and national levels.

STD partner notification and referral in primary level health centers in Nairobi, Kenya.

BACKGROUND: Controlling sexually transmitted diseases requires that partners of patients with a sexually transmitted disease be notified and treated. However, many countries in the developing world lack the infrastructure and resources for effective partner referral. GOAL OF THIS STUDY: To provide information on rates of partner referral in primary-level health centers in Kenya, to identify characteristics of patients with sexually transmitted diseases who inform their partners about the need for treatment, and to evaluate the impact of a brief counseling intervention on rates of partner notification. STUDY DESIGN: Two-hundred-fifty-four patients presenting for treatment of a sexually transmitted disease were given 5 to 10 minutes of additional counseling on the importance of referring partners for sexually transmitted disease treatment. All patients who returned for follow-up 1 week later were interviewed to determine whether they had notified their sex partners. RESULTS: Sixty-eight percent of patients who returned for follow-up reported they had referred their partners for treatment of a sexually transmitted disease. The highest rates of partner notification occurred among women attending maternal child health/family planning clinics and married men and women attending general outpatient clinics. CONCLUSION: Strengthening and directing counseling toward women in maternal child health/family planning clinics and married men and women in general clinics may be an effective and inexpensive way to increase partner notification in the developing world.

PIP: In developing countries, patient referral is a more feasible means of notifying partners of sexually transmitted disease (STD) clients than the costly, labor-intensive provider referral approach. However, enhancement strategies such as education and counseling, contact cards, educational materials, follow-up, and monetary incentives may be necessary. To assess the impact of brief counseling on patient referral rates, a study was conducted at five primary health care centers in low-income areas of Nairobi, Kenya. All 254 STD patients who attended the clinic in a two-week period in 1992 were enrolled in the study. Subjects were given 5-10 minutes of counseling, asked to identify their sexual partners, and given a return appointment for the following week. Of the 93 patients who returned to the clinic and provided partner referral data, 63 (68%) reported they informed their partner of the need for STD treatment and 54 (58%) claimed that their partners had been treated. Multivariate analysis indicated that partner notification rates were highest for females, married individuals or those with regular partners, and maternal-child health/family planning clinic patients. Although 84% of unmarried men, 66% of unmarried women, and 47% of married men were infected by a casual sex partner, only 35% of those in the casual partner group attempted notification. Before the study, only 15% of partners presented to the clinics for treatment as a result of partner referral. This provides some evidence of the effectiveness of the counseling strategy, at least for married men and women, although more detailed guidelines on methods of partner notification are recommended.

Social epidemiology in Africa: slowing the heterosexual transmission of AIDS.

PIP: Analyzing why the rate of transmission of AIDS varies widely in Africa is the basis for designing strategies for intervention. Promiscuity, i.e. high rates of sex partner change, is not the only reason for rapid transmission, but it is a prerequisite for the explosive spread seen in certain groups. High frequency groups include mobile single men and prostitutes. Research and strategies must focus on sex practices, concepts of personal vulnerability, and possibility of behavioral change. The sexually transmitted diseases that are thought to increase susceptibility to HIV, i.e., genital ulcer diseases, can be controlled with appropriate strategies. Male circumcision is associated with lower HIV seroprevalence. Thus strategies must be concentrate on sustained prevention among high STD transmitters, providing early, effective care for STDs, increasing economic alternatives for women, and offering voluntary circumcision where culturally acceptable.^ieng

Response of a sexually transmitted infection epidemic to a treatment and prevention programme in Nairobi, Kenya.

Although it seems possible in a developing country context such as Kenya, given appropriate inputs and a sound approach, to shift a sexually transmitted disease (STI) epidemic from phase II to III, it is not entirely clear how to go beyond this stage, to low levels of endemicity or even elimination. Perhaps the most important challenge now is to expand STI treatment and community STI/HIV prevention programmes to a much larger scale. Although successful programmes have been implemented in many areas of sub-Saharan Africa on a small scale, a significant impact in reducing the STI/HIV burden will not occur until programme reach is expanded to district, provincial, and national levels.

Sexually transmitted infections and vaginal douching in a population of female sex workers in Nairobi, Kenya.

OBJECTIVE: To assess the association between vaginal douching and sexually transmitted infections (STI) among a group of female sex workers (FSWs) in Nairobi, Kenya. METHODS: This study was part of a randomised, placebo controlled trial of monthly prophylaxis with 1 g of azithromycin to prevent STIs and HIV infection in a cohort of Nairobi FSWs. Consenting women were administered a questionnaire and screened for STIs. RESULTS: The seroprevalence of HIV-1 among 543 FSWs screened was 30%. HIV infection was significantly associated with bacterial vaginosis (BV), trichomoniasis, gonorrhoea, and the presence of a genital ulcer. Regular douching was reported by 72% of the women, of whom the majority inserted fluids in the vagina, generally after each sexual intercourse. Water with soap was the fluid most often used (81%), followed by salty water (18%), water alone (9%), and a commercial antiseptic (5%). Douching in general and douching with soap and water were significantly associated with bacterial vaginosis (p = 0.05 and p = 0.04 respectively). There was a significant trend for increased frequency of douching and higher prevalence of BV. There was no direct relation observed between douching and risk for HIV infection or other STIs. CONCLUSION: The widespread habit of douching among African female sex workers was confirmed. The association between vaginal douching and BV is of concern, given the increased risk of HIV infection with BV, which has now been shown in several studies. It is unclear why we could not demonstrate a direct association between douching and HIV infection. Further research is required to better understand the complex relation between douching, risk for bacterial vaginosis, and risk for HIV and other STIs.

Acute sexually transmitted infections increase human immunodeficiency virus type 1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 cell counts.

In Kenya, the median incubation time to AIDS in seroconverting sex workers is 4 years; this incubation time is specific to female sex workers. We studied the influence of acute sexually transmitted infections (STIs) on several immunologic parameters in 32 human immunodeficiency virus type 1 (HIV-1)-positive and 10 HIV-1-negative women sex workers who were followed for 1-5 months. Plasma cytokines, soluble cytokine receptors, CD4 and CD8 T cell counts, and HIV-1 plasma viremia were quantitated before, during, and after episodes of STI. Increases in interleukin (IL)-4, IL-6, IL-10, soluble tumor necrosis factor (TNF)-alpha, and viremia and a decline in CD4(+) T cell counts occurred during gonococcal cervicitis and returned to baseline after treatment. Increases in viremia correlated with increased IL-4 and decreased IL-6 concentrations. Similar changes were seen among women with acute pelvic inflammatory disease. Acute bacterial STI resulted in increased HIV-1 viremia. This may be mediated through increased inflammatory cytokines or through modulation of immune responses that control HIV-1 viremia.