Results of a cluster randomized trial testing the Systems Analysis and Improvement Approach to increase cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya. METHODS: Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics. RESULTS: In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45-1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74-1.75). CONCLUSIONS: The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA's implementation with significant disruptions in FP care delivery during the trial. While SAIA's data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.

Fertility Desire and Associations with Condomless Sex, Antiretroviral Adherence, and Transmission Potential in a Cohort of Kenyan Women Living with HIV in Sero-discordant Relationships: A Mixed Methods Study.

For women living with HIV (WLH) in serodiscordant partnerships, decisions about childbearing can challenge condom use and antiretroviral adherence. In a prospective cohort of 148 WLH in serodiscordant partnerships, 58 (39%) wanted more children in the future but were not currently trying to conceive (fertility desire), and 32 (22%) were currently trying to become pregnant (fertility intent). Detection of prostate specific antigen (PSA) in vaginal secretions, a marker for recent condomless sex, was lowest in women with fertility desire and highest in women with fertility intent. Detectable viral load followed a similar pattern. Risk of HIV transmission, when condomless sex and PSA detection occurred concurrently, was three to fourfold higher at visits with fertility intent compared to visits with fertility desire. Qualitative interviews underscored the importance women place on childbearing and suggested that they had limited information about the role of antiretroviral therapy in reducing sexual HIV transmission.

A cross-sectional study of the prevalence, barriers, and facilitators of cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the most common cancer in sub-Saharan Africa. With appropriate screening and treatment, cervical cancer can be prevented. In Kenya, cervical cancer screening is recommended for all women of reproductive age who visit a health facility. In particular, the Kenyan Ministry of Health has tasked family planning clinics and HIV clinics with implementing cervical cancer screening as part of the overall cervical cancer screening strategy. A cross-sectional survey was conducted to understand cervical cancer screening practices and explore clinic-level barriers and facilitators to screening in family planning clinics (FP) in Mombasa County, Kenya. METHODS: Structured interviews were conducted with randomly sampled FP clinic managers to collect information about clinic size, location, type, management support, infrastructure, screening practices, and availability of screening commodities. Data were abstracted from FP registers for a 15-month period from October 1, 2017 until December 31, 2018 to understand cervical cancer screening prevalence. Generalized linear models were used to calculate prevalence ratios (PR) and identify clinic-level correlates of reporting any cervical cancer screening. RESULTS: A total of 70 clinics were sampled, 54% (38) were urban and 27% (19) were public facilities. The median number of staff in a clinic was 4 (interquartile range [IQR] 2-6) with a median of 1 provider trained to perform screening (IQR 0-3). Fifty-four percent (38/70) of clinic managers reported that their clinics performed cervical cancer screening. Of these, only 87% (33) and 71% (27) had dependable access to speculums and acetic acid, respectively. Being a public FP clinic was associated with higher prevalence of reported screening (14/38 [37%] vs 6/32 [16%]; prevalence rate ratio [PR] 1.57, 95%CI 1.05-2.33). Clinics that reported cervical cancer screening were much more likely to have at least one provider trained to perform cervical cancer screening (84%, 32/38) compared to clinics that did not report screening (28%, 9/32; PR 3.77, 95%CI 1.82-7.83). CONCLUSION: Integration of cervical cancer screening into FP clinics offers great potential to reach large numbers of reproductive-aged women. Increasing training of healthcare providers and ensuring adequate commodity supplies in FP clinics offer concrete solutions to increase screening in a largely unscreened population.

Performance of family planning clinics in conducting recommended HIV counseling and testing in Mombasa County, Kenya: a cross-sectional study.

BACKGROUND: A high proportion of African women utilize family planning (FP) services. Accordingly, incorporating HIV testing into FP services may strategically target the first WHO 90-90-90 goal of 90% of people living with HIV knowing their status. METHODS: The objective of this analysis was to determine the proportion of new FP clients counseled and tested for HIV, as well as correlates of HIV testing, in a random sample of 58 FP clinics in Mombasa County, Kenya. Structured interviews of FP clinic managers collected data on characteristics of FP clinics and staff. Study staff performed a 3-month review of FP registers, summarizing new client HIV testing and counseling (HTC). Because overall rates of HTC were quite low, a binary variable was created comparing clinics performing any HIV counseling and/or testing to clinics performing none. Generalized linear models were used to calculate prevalence ratios (PR) and identify correlates of HTC. Factors associated with any HTC with a p-value < 0.10 in univariate analysis were included in a multivariate analysis. RESULTS: Of the 58 FP clinics, 26 (45%) performed any counseling for HIV testing, and 23 (40%) performed any HIV testing. Counseling for HIV testing was conducted for 815/4389 (19%) new clients, and HIV testing was performed for 420/4389 (10%). Clinics without trained HIV testing providers uniformly did not conduct HIV counseling and/or testing (0/12 [0%]), while 27/46 (59%) of clinics with ≥1 provider performed some HTC (p < 0.001). In the subset of 46 clinics with ≥1 trained HIV testing provider, correlates of performing HTC included being a public versus non-public clinic (PR 1.70 95%CI 1.01-2.88), and having an HIV comprehensive care center (CCC) onsite (PR 2.05, 95%CI 1.04-4.06). CONCLUSION: Trained HIV testing providers are crucial for FP clinics to perform any HTC. Approaches are needed to increase routine HTC in FP clinics including staffing changes and/or linkages with other testing services (in standalone VCT services or lab facilities) in order to improve the implementation of existing national guidelines. A future cluster randomized trial is planned to test an implementation strategy, the Systems Analysis and Improvement Approach (SAIA) to increase HTC in FP clinics.

Brief Report: Association Between Menopause and Unprotected Sex in High-Risk HIV-Positive Women in Mombasa, Kenya.

OBJECTIVE: Many HIV-positive women now live well beyond menopause. Postmenopausal women are no longer at risk for pregnancy, and some studies suggest that they may use condoms less often than premenopausal women. This study tests the hypothesis that, in HIV-positive women who report trading sex for cash or in-kind payment, unprotected sex is more common at postmenopausal visits compared with premenopausal visits. DESIGN: Prospective cohort study of HIV-positive women ≥16 years old in Mombasa, Kenya. METHODS: At enrollment and monthly follow-up visits, participants completed a standardized interview. Study clinicians collected genital samples at enrollment and quarterly visits. Menopausal status was assessed annually. The primary outcome of unprotected sex was determined by detection of prostate specific antigen (PSA) in vaginal secretions. RESULTS: This study followed 404 HIV-positive women who contributed 2753 quarterly examination visits. Detection of PSA was less frequent at postmenopausal visits compared with premenopausal visits [55/554, 10.5% versus 394/2199, 17.9%; relative risk (RR) 0.58, 95% confidence interval (CI): 0.39 to 0.87]. Adjusting for age diminished the association between menopause and PSA detection (adjusted RR 0.73, 95% CI: 0.47 to 1.14). At visits where women reported sexual activity in the past week, they reported similar rates of 100% condom use at postmenopausal and premenopausal visits (RR 0.99, 95% CI: 0.87 to 1.13). CONCLUSIONS: In this population of high-risk HIV-positive Kenyan women, postmenopausal status was not associated with a greater risk of unprotected sex. The relationship between menopause and unprotected sex is likely context specific and may differ with varying risk groups, regions, and levels of exposure to sexual health education.

Alcohol Use and Associations With Biological Markers and Self-Reported Indicators of Unprotected Sex in Human Immunodeficiency Virus-Positive Female Sex Workers in Mombasa, Kenya.

BACKGROUND: Studies of alcohol use and sexual behavior in African populations have primarily been cross-sectional, used nonvalidated measures of alcohol use, or relied on self-reported sexual risk endpoints. Few have focused on human immunodeficiency virus (HIV)-positive women. METHODS: Longitudinal data were collected from a cohort of HIV-positive Kenyan female sex workers. At enrollment and annual visits, participants were asked about past-year alcohol use using the Alcohol Use Disorders Identification Test (AUDIT). The primary endpoint was detection of prostate-specific antigen (PSA) in vaginal secretions at quarterly examinations. Associations between hazardous/harmful alcohol use (AUDIT score ≥7), PSA detection, and secondary measures of sexual risk were evaluated using generalized estimating equations with a log binomial regression model. RESULTS: A total of 405 women contributed 2750 vaginal samples over 606 person-years of follow-up. Hazardous/harmful alcohol use was reported at 16.6% of AUDIT assessments and was associated with higher risk of PSA detection (relative risk 1.50; 95% confidence interval, 1.11-2.01) relative to no alcohol use. This association was attenuated and no longer statistically significant, after adjusting for age, work venue, intimate partner violence, depression, and partnership status (adjusted relative risk, 1.13; 95% confidence interval, 0.82-1.56). In exploratory analyses, alcohol use was associated with self-report of unprotected sex and with sexually transmitted infection acquisition. CONCLUSIONS: Although hazardous/harmful alcohol use was not associated with detection of PSA in adjusted analysis, associations with secondary outcomes suggest that alcohol use is at least a marker of sexual risk behavior.

Oral HHV-8 replication among women in Mombasa, Kenya.

Human herpesvirus-8 (HHV-8) replication in the oropharynx may play an important role in HHV-8 transmission and contribute to the development of Kaposi sarcoma (KS) in some individuals. Studies in the United States and Europe report high rates of HHV-8 DNA detection in saliva of HHV-8 infected men, but little is known about the natural history of HHV-8 among persons in sub-Saharan Africa, where prevalence of HHV-8 infection and KS is greatest. To address this gap, this study evaluated oral HHV-8 replication in a cohort of 40 HHV-8 seropositive Kenyan women. Study clinicians collected daily oral swabs from participants for up to 30 consecutive days, and swab samples were tested for HHV-8 DNA using quantitative, real-time polymerase chain reaction. HHV-8 was detected at least once in 27 (68%) participants, and the overall shedding rate was 23%. On days with HHV-8 detection, mean HHV-8 quantity was 4.5 log10 copies/ml. Among HIV-infected women, CD4 count ≥500 cells/mm(3) versus <500 cells/mm(3) was associated with higher HHV-8 copy number (4.8 log10 copies/ml vs. 3.4 log10 copies/ml; coef 1.2 [95% CI, 0.5-1.9]; P = 0.001) and a higher HHV-8 shedding rate (49% vs.12%; RR, 4.2 [95% CI, 0.8-21.4]; P = 0.08). No other factors were associated with HHV-8 shedding rate or copy number. The study demonstrates high rates and quantity of HHV-8 in the oropharynx of HHV-8 seropositive African women. These findings support the observation that oral replication is an essential feature of HHV-8 infection, with likely implications for HHV-8 transmission and KS pathogenesis.

Systemic cytokine levels show limited correlation with risk of HIV-1 acquisition.

It has been hypothesized that immune activation and inflammation may increase HIV-1 susceptibility, and that cytokines may be useful biomarkers for risk. Within a prospective cohort, we conducted a nested case-control analysis of plasma cytokine levels among women who acquired HIV-1 <3 months after sampling, compared with 3 different control groups. We observed associations between lower interleukin (IL)-6 and IL-10 and higher IL-7 levels with HIV-1 acquisition, however, these associations were inconsistent when comparing with different control groups. Inconsistent results within our study and among previous studies suggest that reproducible findings are needed before cytokines are useful biomarkers for HIV-1 susceptibility.

Establishing and sustaining a healthy vaginal environment: analysis of data from a randomized trial of periodic presumptive treatment for vaginal infections.

Data from a randomized trial of oral periodic presumptive treatment (PPT) to reduce vaginal infections were analyzed to assess the effect of the intervention on a healthy vaginal environment (normal flora confirmed by Gram stain with no candidiasis or trichomoniasis). The incidence of a healthy vaginal environment was 608 cases per 100 person-years in the intervention arm and 454 cases per 100 person-years in the placebo arm (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.17-1.58). Sustained vaginal health (healthy vaginal environment for ≥3 consecutive visits) was also more frequent in the intervention arm (HR, 1.69; 95% CI, 1.23-2.33). PPT is effective at establishing and sustaining a healthy vaginal environment.

Implementation of clinic-based modified-directly observed therapy (m-DOT) for ART; experiences in Mombasa, Kenya.

The effectiveness of modified-directly observed therapy (m-DOT), an adherence support intervention adapted from TB DOTS programmes, has been documented. Describing the implementation process and acceptability of this intervention is important for scaling up, replication in other settings and future research. In a randomised trial in Mombasa, Kenya, patients were assigned to m-DOT or standard of care for 24 weeks. m-DOT entailed twice weekly visits to a health centre for medication collection, ongoing adherence counselling and nurse-observed pill ingestion. Community health workers (CHWs) traced non-attendees, observing pill taking at participant's home. Using process indicators and a semi-structured questionnaire, implementation of m-DOT was evaluated among 94 participants who completed 24 weeks m-DOT (81%; 94/116). Two-thirds of m-DOT recipients were female (64%; 74/116) and a mean 37 years (SD = 7.8). Selection of the m-DOT observation site was determined by proximity to home for 73% (69/94), with the remainder choosing sites near their workplace, or due to perceived high-quality services. A median 42 of 48 scheduled m-DOT visits (IQR = 28-45) were attended. Most found m-DOT is very useful (87%; 82/94) and had positive attitudes to the services. A high proportion received CHWs home visits (96%; 90/94) and looked forward to these. Use of CHWs and several satellite observation sites facilitated provision of services closer to patient's homes. A substantial number, however, thought 24 weeks of m-DOT was too long (43%; 42/94). Our experience suggests that m-DOT services could be implemented widely and are acceptable if delivered with adequate attention to coordination, provision of a broad set of interventions, shifting tasks to less-specialised workers and integration within the health system. m-DOT programmes should utilise existing resources while simultaneously expanding capacity within communities and the public sector. These findings could be used to inform replication of such services and to improve the design of m-DOT in future studies.

Perceived stigma among patients receiving antiretroviral treatment: a prospective randomised trial comparing an m-DOT strategy with standard-of-care in Kenya.

HIV and AIDS remain highly stigmatised. Modified directly observed therapy (m-DOT) supports antiretroviral treatment (ART) adherence but little is known about its association with perceived stigma in resource-constrained settings. In 2003, 234 HIV-infected adults enrolled in a two-arm randomised trial comparing a health centre-based m-DOT strategy with standard self-administration of ART. Data on perceived stigma were collected using Berger's HIV stigma scale prior to starting ART and after 12 months. This was a secondary analysis to examine whether perceived stigma was related to treatment delivery. Perceived stigma scores declined after 12 months of treatment from a mean of 44.9 (sd=7.6) to a mean of 41.4 (sd=7.7), (t=6.14, P<0.001). No differences were found between the mean scores of participants in both study arms. Also, no difference in scores was detected using GLM, controlling for socio-demographic characteristics and baseline scores. Findings indicate that a well managed clinic-based m-DOT does not increase perceived HIV-related stigma.

Short- and long-term efficacy of modified directly observed antiretroviral treatment in Mombasa, Kenya: a randomized trial.

OBJECTIVES: To determine short- and long-term efficacy of modified directly observed therapy (m-DOT) on antiretroviral adherence. DESIGN: Randomized controlled trial. SETTING AND ANALYTIC APPROACH: From September 2003 to November 2004, 234 HIV-infected adults were assigned m-DOT (24 weeks of twice weekly health center visits for nurse-observed pill ingestion, adherence support, and medication collection) or standard care. Follow-up continued until week 72. Self-reported and pill-count adherence and, secondarily, viral suppression and body mass index measures are reported. Generalized estimating equations adjusted for intraclient clustering and covariates were used. RESULTS: During weeks 1-24, 9.1% (9/99) of m-DOT participants reported missing doses compared with 19.1% (20/105) of controls (P = 0.04) and 96.5% (517/571) of m-DOT pill-count measures were >or=95% compared with 86.1% (445/517) in controls [adjusted odds ratio = 4.4; 95% confidence interval (CI) = 2.6 to 7.5; P < 0.001. Adherence with m-DOT was 4.8 times greater (95% CI = 2.7 to 8.6; P < 0.001) with adjustment for depression and HIV-related hospitalization. In weeks 25-48, adherence with m-DOT (488/589) was similar to controls (507/630). Viral suppression at 48 weeks was 2.0 times (95% CI = 0.8 to 5.2; P = 0.13) as likely in m-DOT participants as controls. M-DOT patients had larger body mass index increases at 24 weeks (2.2 vs 1.4 kg/m3; P = 0.014). Viral suppression was more likely at week 48 (21/25 vs 13/22; P = 0.057) and week 72 (27/30 vs 15/23; P = 0.027) among depressed participants receiving m-DOT. CONCLUSIONS: M-DOT increased adherence, most notably among depressed participants.

HIV-1 subtype A envelope variants from early in infection have variable sensitivity to neutralization and to inhibitors of viral entry.

BACKGROUND: An effective HIV-1 vaccine or microbicide must block the transmitted virus variants that initially establish a new infection; consequently, it is critical that such viruses be isolated and characterized. OBJECTIVE: To evaluate HIV-1 envelope variants from early in infection from individuals infected heterosexually with subtype A HIV-1 for their sensitivity to antibody-mediated neutralization and to inhibitors of viral entry. METHODS: Full-length subtype A HIV-1 envelope clones from 28-75 days postinfection were used to generate pseudoviruses for infection studies. The susceptibility of these pseudoviruses to neutralization by autologous and heterologous plasma and by monoclonal antibodies was examined. The sensitivity of these pseudoviruses to PSC-RANTES and TAK-779, inhibitors of CCR5, and to soluble CD4 (sCD4) was also evaluated. RESULTS: Pseudoviruses with subtype A HIV-1 envelopes from early in infection demonstrated a broad range of neutralization sensitivities to both autologous and heterologous plasma. However, neutralization by the monoclonal antibodies b12, 2G12, 4E10 and 2F5 was generally poor; notably, none of the 14 early virus variants were neutralized by 2G12 and only one was neutralized by b12. Viruses bearing these early CCR5-using envelopes were generally sensitive to the CCR5 inhibitors PSC-RANTES and TAK-779, but they demonstrated more variable sensitivity to sCD4. CONCLUSIONS: These subtype A HIV-1 variants, representing the viruses that must be blocked by antibody-based prevention strategies, vary in their susceptibility to neutralization. A subset of these HIV-1 variants from early in infection will be useful for screening candidate vaccines and microbicides.

Shedding of human herpesvirus 8 in oral and genital secretions from HIV-1-seropositive and -seronegative Kenyan women.

Polymerase chain reaction was used to determine the prevalence and correlates of human herpesvirus 8 (HHV8) in saliva, mouth, cervical, vaginal, plasma, and peripheral-blood mononuclear cell (PBMC) samples from 174 HHV8-seropositive female prostitutes in Mombasa, Kenya. The prevalence of detection of HHV8 was 32% in saliva samples, 28% in mouth swabs, 4% in cervical swabs, 2.3% in vaginal swabs, 9% in plasma samples, and 18% in PBMC samples. Human immunodeficiency virus type 1 (HIV-1) seropositivity was associated with detection of HHV8 from any mucosal surface (odds ratio, 2.1 [95% confidence interval, 1.1-4.0]). In HIV-1-seropositive women, there was no association between detection of HHV8 and either CD4 count or HIV-1 viral load.

Cyclic shedding of HIV-1 RNA in cervical secretions during the menstrual cycle.

The association between hormone fluctuations during the menstrual cycle and human immunodeficiency virus type 1 (HIV-1) RNA shedding in cervical and vaginal secretions was examined daily for 17 HIV-1-seropositive women, for the duration of 1 cycle. Serum levels of RNA were evaluated 3 times/week. A marginally significant positive correlation between serum levels of progesterone and serum levels of HIV-1 RNA (P=.04) was observed. Cervical virus levels were significantly correlated with the number of days from the midcycle surge in luteinizing hormone (LH) (P=.008). The lowest levels of cervical HIV-1 RNA were present at the LH surge, and this nadir was followed by an increase in virus levels that reached a maximum before the start of menses. In contrast, there was no significant association between the number of days from the LH surge and the level of HIV-1 RNA in vaginal secretions (P=.4). These data support the hypothesis that the level of HIV-1 RNA in cervical secretions is influenced by the menstrual cycle, and they suggest that the risk of heterosexual transmission of HIV-1 may increase as menses is approached.

Human herpesvirus 8 seroconversion in Kenyan women by enzyme-linked immunosorbent assay and immunofluorescence assay.

BACKGROUND: Human herpesvirus 8 (HHV-8) antibody tests vary in reported sensitivity and specificity, depending on the population tested and the assay. OBJECTIVE: The purpose of this study was to compare the ability to detect seroconversion to HHV-8 in a cohort of HHV-8 seronegative female commercial sex workers in Kenya using three tests: HHV-8 viral lysate-based enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay for HHV-8 lytic antigens (IFA-lytic) and IFA for latent nuclear antigens (IFA-LANA). STUDY DESIGN: By ELISA, 16 women from a prospective cohort of commercial sex workers were identified as seroconverting to HHV-8. A total of 124 post-enrollment samples from these 16 women as well as the enrollment samples were tested for HHV-8 antibodies by all three assays to monitor seroconversion. RESULTS: Of 16 women with apparent seroconversion by ELISA, 8 had a rise in IFA-lytic titers either concomitant with or prior to the first positive ELISA sample and no initial LANA by IFA. Five of the 16 women were IFA-LANA positive at entry, indicating prior infection with HHV-8. Three women had no evidence of seroconversion by either IFA-lytic or IFA-LANA and two of these three had increased ELISA reactivity concomitant with HIV-1 infection. CONCLUSIONS: Conversion from a negative to a positive ELISA result for HHV-8 antibody indicated seroconversion in only half of the study cohort of 16 women when IFA-lytic and IFA-LANA results were considered. The IFA-lytic assay was more sensitive than ELISA for early antibody responses. The IFA-LANA was positive in some women who had neither IFA-lytic nor ELISA antibodies suggesting it may be a marker for latent infections. Presumptive identification of incident HHV-8 infection by ELISA screening followed by IFA-lytic testing to confirm the positive test and IFA-LANA to rule out prior infection provides the most accurate documentation of HHV-8 seroconversion.

Diversity of the human immunodeficiency virus type 1 (HIV-1) env sequence after vertical transmission in mother-child pairs infected with HIV-1 subtype A.

Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1016-bp fragment of the env gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.

Human herpesvirus 8: seroprevalence and correlates in prostitutes in Mombasa, Kenya.

Human herpesvirus 8 (HHV-8) infection is very prevalent in sub-Saharan Africa, but the role of sexual transmission has not been well characterized. HHV-8 seroprevalence and correlates were evaluated in a cohort of female prostitutes in Mombasa, Kenya. Between February 1993 and January 2000, stored plasma samples taken from 736 women were tested, by whole-virus ELISA assay, for the presence of HHV-8 antibodies; of these 736 women, 633 were included in the analysis of correlates of HHV-8 infection; and, of these 633, 44.1% were seropositive for HHV-8 antibodies. In univariate analysis, age, years of education, years of prostitution, workplace, hormonal contraception, intrauterine-device use, alcohol consumption, syphilis, and gonorrhea were all significantly associated with the presence of HHV-8 antibodies. In a multivariate model, older age, fewer years of education, and 2 markers of high-risk sexual behavior-namely, alcohol consumption and gonorrhea-were each independently associated with HHV-8 seropositivity. These results suggest that heterosexual transmission may contribute to acquisition of HHV-8 infections in this African population of prostitutes.

Correlates of human herpesvirus 8 seropositivity among heterosexual men in Kenya.

BACKGROUND: Several studies have suggested that sexual transmission of human herpesvirus 8 (HHV-8) occurs among homosexual men in developed countries. However, few studies have examined heterosexual HHV-8 transmission, especially among African populations in which HHV-8 is endemic. OBJECTIVES: To determine the seroprevalence and correlates of HHV-8 infection among heterosexual African men. DESIGN: Cross-sectional study. METHODS: Participants were 1061 men enrolled in a prospective cohort study of risk factors for HIV-1 acquisition among trucking company employees in Mombasa, Kenya. Stored frozen sera from the study baseline visit were tested for antibodies to HHV-8 by whole-virus lysate ELISA. RESULTS: HHV-8 seroprevalence was 43%. In multivariate logistic regression analysis, HHV-8 infection was independently associated with older age [for men aged 30-39 years: odds ratio (OR), 1.5; 95% confidence interval (CI), 1.1-2.0; for men aged > or = 40 years: OR, 1.7; 95% CI, 1.1-2.7, compared with men aged < 30 years], Christian religion (OR, 1.6; 95% CI, 1.2-2.1), being uncircumcised (OR, 1.5; 95% CI, 1.0-2.2), and ever having syphilis (OR, 2.2; 95% CI, 1.4-3.5). Ever having used condoms was associated with decreased likelihood of infection (OR, 0.7; 95% CI, 0.6-1.0). Seropositivity was not significantly related to other sexual behaviors characterized or to HIV-1 status. CONCLUSIONS: HHV-8 seropositivity is common in this population and increases with age, suggesting on-going transmission during adulthood. Infection was more common among men who were uncircumcised or who had ever had syphilis and was less common among those who had ever used condoms, suggesting that sexual factors may play a role in HHV-8 transmission. Prospective studies of HHV-8 acquisition in heterosexual African populations are needed to demonstrate whether safer sexual practices can reduce transmission.