Contributions of side effects to contraceptive discontinuation and method switch among Kenyan women: a prospective cohort study.

OBJECTIVE: To determine the contribution of specific contraceptive side effects to method switch and modern-method discontinuation among Kenyan women. DESIGN: A prospective cohort study. SETTING: Five counties in Western Kenya. PARTICIPANTS: Women aged ≥18 years old and emancipated female minors ≥14 years old using modern, reversible contraception were recruited while attending 10 public health facilities. METHODS: Patient-reported adverse effect symptoms, method switch and discontinuation were reported through weekly text message-based surveys for 24 weeks. MAIN OUTCOME MEASUREMENTS: Prevalence, hazards ratio (HR). RESULTS: Among 825 women, 44% were using implants, 43% injectables, 7% an intrauterine device and 6% oral contraceptive pills at enrolment. Most (61%) women were continuing a method used in the previous month. During the 24-week follow up, incidence of contraceptive switch was 61.3 per 100 person-years (95% confidence interval [CI] 52.4-71.8) and incidence of discontinuation was 38.5 per 100 person-years (95% CI 31.6-47.0). On average, one-quarter (prevalence [Pr] 0.24, 95% CI 0.22-0.26) of participants reported side effects or method problems weekly, with sexual side effects the most prevalent symptom (Pr 0.15, 95% CI 0.13-0.16). Lack of expected bleeding was associated with higher risk of method switch (adjusted hazard ratio [aHR] 2.36, 95% CI 1.22-4.57). Risk of all-modern method discontinuation was higher among women experiencing irregular bleeding (aHR 2.39, 95% CI 1.20-4.77), weight changes (aHR 2.72, 95% CI 1.47-4.68) and sexual side effects (aHR 2.42, 95% CI 1.40-4.20). CONCLUSIONS: Addressing irregular bleeding, weight changes and sexual side effects through development of new products that minimise these specific side effects and anticipatory counseling may reduce method-related discontinuation. TWEETABLE ABSTRACT: Bleeding, weight changes, sexual problems associated with discontinuation of #contraception, but many continue despite side effects.

Standardised patient encounters to improve quality of counselling for pre-exposure prophylaxis (PrEP) in adolescent girls and young women (AGYW) in Kenya: study protocol of a cluster randomised controlled trial.

INTRODUCTION: Adolescent girls and young women (AGYW) in sub-Saharan Africa are at high risk of HIV acquisition. Pre-exposure prophylaxis (PrEP) demonstration projects observe that AGYW uptake and adherence to PrEP during risk periods is suboptimal. Judgemental interactions with healthcare workers (HCW) and inadequate counselling can be barriers to PrEP use among AGYW. Improving HCW competency and communication to support PrEP delivery to AGYW requires new strategies. METHODS AND ANALYSIS: PrEP Implementation for Young Women and Adolescents Program-standardised patient (PrIYA-SP) is a cluster randomised trial of a standardised patient actor (SP) training intervention designed to improve HCW adherence to PrEP guidelines and communication skills. We purposively selected 24 clinics offering PrEP services under fully programmatic conditions in Kisumu County, Kenya. At baseline, unannounced SP 'mystery shoppers' present to clinics portraying AGYW in common PrEP scenarios for a cross-sectional assessment of PrEP delivery. Twelve facilities will be randomised to receive a 2-day training intervention, consisting of lectures, role-playing with SPs and group debriefing. Unannounced SPs will repeat the assessment in all 24 sites following the intervention. The primary outcome is quality of PrEP counselling, including adherence to national guidelines and communication skills, scored on a checklist by SPs blinded to intervention assignment. An intention-to-treat (ITT) analysis will evaluate whether the intervention resulted in higher scores within intervention compared with control facilities, adjusted for baseline SP scores and accounting for clustering by facility. We hypothesise that the intervention will improve quality of PrEP counselling compared with standard of care. Results from this study will inform guidelines for PrEP delivery to AGYW in low-resource settings and offer a potentially scalable strategy to improve service delivery for this high-risk group. ETHICS AND DISSEMINATION: The protocol was approved by institutional review boards at Kenyatta National Hospital and University of Washington. An external advisory committee monitors social harms. Results will be disseminated through peer-reviewed journals and presentations. TRIAL REGISTRATION NUMBER: NCT03875950.

Mycobacterium tuberculosis bacteremia in adults and children: a systematic review and meta-analysis.

UNLABELLED: SETTINGp: Among human immunodeficiency virus (HIV) infected adults living in tuberculosis (TB) endemic settings, Mycobacterium tuberculosis is a common cause of bloodstream infections. Although young children have an increased propensity for M. tuberculosis dissemination, M. tuberculosis bacteremia is infrequently described in children. OBJECTIVE: To determine the prevalence of M. tuberculosis bacteremia in adult and pediatric patients and to examine sources of heterogeneity between estimates. DESIGN: Systematic review and meta-analysis. RESULTS: Of 1077 reviewed abstracts, 27 publications met the inclusion criteria, yielding 29 independent M. tuberculosis bacteremia prevalence estimates: 22 in adults, 6 in children, and 1 not stratified by age group. The random effects pooled M. tuberculosis bacteremia prevalence in adults was 13.5% (95%CI 10.8-16.2) and 0.4% (95%CI 0-0.9) in children (P for difference = 0.004). Restricting analyses to HIV-infected participants, pooled M. tuberculosis bacteremia prevalence from 21 adult studies was 15.5% (95%CI 12.5-18.5) and 0.8% (95%CI 0-1.8) in three pediatric studies (P = 0.001). Inclusion of pre-determined study-level confounders did not account for observed differences in M. tuberculosis bacteremia prevalence between age groups. CONCLUSION: While M. tuberculosis bacteremia appears relatively common in adults, particularly those with HIV infection, bloodstream M. tuberculosis appears to be rare in children.

CCR5, RANTES and SDF-1 polymorphisms and mother-to-child HIV-1 transmission.

Summary Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were followed with their infants in Nairobi, we found no associations between maternal genetic polymorphisms in CCR5 (59029G/A, 59353T/C, 59356T/C, 59402G/A), RANTES (-403G/A) and SDF-1 (3'801G/A) and mother-to-child HIV-1 transmission; plasma, cervical and breastmilk viral loads; or breastmilk chemokine concentrations.

HIV testing men in the antenatal setting: understanding male non-disclosure.

Prevention of infant HIV is a powerful incentive for maternal HIV diagnosis and an opportunity to increase male HIV testing and disclosure of HIV status within couples. We examined male HIV disclosure in couples who attended a Nairobi antenatal clinic (ANC), had individual HIV testing, and were counselled to disclose to their partner. At two-week follow-up, men and women independently reported HIV disclosure. Of 2104 women, 1993 requested partner attendance; 313 male partners came, of whom 183 chose individual HIV testing. Of 106 couples who followed up, 93% of both partners reported disclosure by women versus 71% by men (P < 0.0001); 27% of men reported disclosure while their female partner reported not knowing partner HIV status. In these couples, male ANC HIV testing did not result in shared knowledge of HIV status. Couple counselling models that incorporate disclosure may yield greater HIV prevention benefits than offering individual partner HIV testing services at ANC.

Infants with late breast milk acquisition of HIV-1 generate interferon-gamma responses more rapidly than infants with early peripartum acquisition.

Infants infected with HIV-1 after the first month of life have a lower viral set-point and slower disease progression than infants infected before 1 month. We investigated the kinetics of HIV-1-specific CD8(+) T lymphocyte secretion of interferon (IFN)-gamma in infants infected before 1 month of life compared with those infected between months 1 and 12 (late infection). HIV-1 infection was assessed at birth and at months 1, 3, 6, 9 and 12 and timing of infection was determined by HIV-1 gag DNA from dried blood spots and verified by plasma HIV-1 RNA levels. HIV-1 peptide-specific IFN-gamma responses were measured by enzyme-linked immunospot at months 1, 3, 6, 9 and 12. Timing of development of IFN-gamma responses was compared using the log-rank test and Kaplan-Meier survival curves. Infants infected late developed HIV-1-specific CD8(+) T cell responses 2.8 months sooner than infants infected peripartum: 2.3 versus 5.1 months after HIV-1 infection (n = 52, P = 0.04). Late-infected infants had more focused epitope recognition than early-infected infants (median 1 versus 2 peptides, P = 0.03); however, there were no differences in the strength of IFN-gamma responses. In infants infected with HIV-1 after the first month of life, emergence of HIV-1-specific CD8(+) IFN-gamma responses is coincident with the decline in viral load, nearly identical to what is observed in adults and more rapid than in early-infected infants.

Prospective study of correlates of vaginal Lactobacillus colonisation among high-risk HIV-1 seronegative women.

OBJECTIVE: Vaginal colonisation with Lactobacillus species is characteristic of normal vaginal ecology. The absence of vaginal lactobacilli, particularly hydrogen peroxide (H(2)O(2))-producing isolates, has been associated with symptomatic bacterial vaginosis (BV) and increased risk for HIV-1 acquisition. Identification of factors associated with vaginal Lactobacillus colonisation may suggest interventions to improve vaginal health. METHODS: We conducted a prospective cohort study of correlates of vaginal Lactobacillus colonisation among Kenyan HIV-1 seronegative female sex workers. At monthly follow-up visits, vaginal Lactobacillus cultures were obtained. Generalised estimating equations were used to examine demographic, behavioural and medical correlates of Lactobacillus isolation, including isolation of H(2)O(2)-producing strains. RESULTS: Lactobacillus cultures were obtained from 1020 women who completed a total of 8896 follow-up visits. Vaginal washing, typically with water alone or with soap and water, was associated with an approximately 40% decreased likelihood of Lactobacillus isolation, including isolation of H(2)O(2)-producing strains. Recent antibiotic use, excluding metronidazole and treatments for vaginal candidiasis, reduced Lactobacillus isolation by approximately 30%. H(2)O(2)-producing lactobacilli were significantly less common among women with Trichomonas vaginalis infection and those who were seropositive for herpes simplex virus type 2. In contrast, H(2)O(2)-producing lactobacilli were significantly more common among women with concurrent vaginal candidiasis. CONCLUSIONS: Modifiable biological and behavioural factors are associated with Lactobacillus colonisation in African women. Our results suggest intervention strategies to improve vaginal health in women at high risk for HIV-1.

Influence of host resistance on the genetic structure of the white pine blister rust fungus in the western United States.

Cronartium ribicola, the causal agent of white pine blister rust, has been devastating to five-needled white pines in North America since its introduction nearly a century ago. However, dynamic and complex interactions occur among C. ribicola, five-needled white pines, and the environment. To examine potential evolutionary influences on genetic structure and diversity of C. ribicola in western United States, population genetic analyses of C. ribicola were conducted using amplified fragment length polymorphism (AFLP) molecular markers. The fungus was sampled at six sites. Collections for two of the six sites were from separate plantings of resistant-selected western white pine and sugar pine. Heterozygosity based on polymorphic loci among populations ranged from 0.28 to 0.40, with resistant-selected plantations at the extremes. Genetic differentiation was also highest between these two populations. Principal coordinates analysis and Bayesian assignment placed most isolates that are putative carriers of virulence to major-gene resistance into a discernable cluster, while other isolates showed no clustering by site or host species. These results indicate that C. ribicola in western North America is not genetically uniform, despite its presumed single site of introduction and relatively brief residence. Moreover, major-gene resistance appears to have imposed strong selection on the rust, resulting in reduced genetic diversity. In contrast, no evidence of selection was observed in C. ribicola from hosts that exhibit only multigenic resistance.

Why are predators more sensitive to habitat size than their prey? Insights from bromeliad insect food webs.

Ecologists have hypothesized that the exponent of species-area power functions (z value) should increase with trophic level. The main explanation for this pattern has been that specialist predators require prior colonization of a patch by their prey, resulting in a compounding of the effects of area up trophic levels. We propose two novel explanations, neither of which assumes trophic coupling between species. First, sampling effects can result in different z values if the abundances of species differ (in mean or evenness) between trophic levels. Second, when body size increases between trophic levels, effects of body size on z values may appear as differences between trophic levels. We test these alternative explanations using invertebrate food webs in 280 bromeliads from three countries. The z value of predators was higher than that of prey. Much of the difference in z values could be explained by sampling effects but not by body size effects. When damselflies occurred in the species pool, predator z values were even higher than predicted, as damselflies avoid small, drought-prone bromeliads. In one habitat, dwarf forests, detrital biomass became decoupled from bromeliad size, which also caused large trophic differences in z values. We argue that there are often simpler explanations than trophic coupling to explain differences in z values between trophic levels.

First Report of the White Pine Blister Rust Fungus, Cronartium ribicola, on Pedicularis bracteosa.

Until recently, Cronartium ribicola J.C. Fisch. was thought to utilize only Ribes spp. (Grossulariaceae) as telial hosts in North America. During 2004, Pedicularis racemosa Dougl. ex Benth. and Castilleja miniata Dougl. (Orobanchaceae) were proven as natural telial hosts at a subalpine site (48.634109°N, 116.570817°W, elevation 1,800 m) near Roman Nose Lake, ID, where whitebark pine (Pinus albicaulis Engelm.) and western white pine (Pinus monticola Dougl. ex D. Don) are aecial hosts, and Pedicularis, Castilleja, and Ribes spp. are common herbs/shrubs (2). During August 2006, teliospore columns typical of C. ribicola or the morphologically indistinguishable (2) C. coleosporioides J.C. Arthur were found on two Pedicularis bracteosa Benth. plants at this site, within 3 m of a large, sporulating canker on whitebark pine. ITS/5.8S rDNA regions were sequenced using detached teliospore column samples from the two plants, ITS1F and ITS4 primers (3), and standard PCR protocols (2). One sample sequence was identified as C. ribicola and the other as C. coleosporioides (GenBank Accession Nos. EF185857 and EF185858, respectively), by exact matches in comparisons with published sequences (2). Artificial inoculation confirmed P. bracteosa's ability to host C. ribicola. Sections of leaves collected near Freezeout Saddle, ID (47.00885°N, 116.00846°W, elev. 1,600 m) were rinsed in water, placed abaxial side up on moistened filter paper in 150-mm petri plates, inoculated with seven diverse sources of urediniospores/aeciospores, misted with distilled water, and incubated at 18°C with 12 h of light. A single leaf section produced urediniospores 17 days and teliospores 26 days after inoculation with one of two Roman Nose aeciospore sources. Urediniospores from this leaf section caused infections on Ribes nigrum L., and teliospore columns yielded a DNA sequence that matched C. ribicola. Though P. bracteosa is confirmed as yet another natural host of C. ribicola in North America, it may be producing less C. ribicola inoculum for pine infection than do the P. racemosa and Ribes spp. telial hosts at the collection site. Uredinia and telia of C. ribicola on P. bracteosa were much less frequent and smaller than those on P. racemosa and Ribes spp. and those of C. coleosporioides on this same host (2). Pedicularis (but not Castilleja) spp. are significant telial hosts of C. ribicola strains at some high elevation sites in eastern Asia (1). Discovery of multiple North American telial hosts in the Orobanchaceae suggests unrecognized complexity in C. ribicola's ability to exploit ecological niches in recently established pathosystems of North America (2). References: (1) G. I. McDonald et al. Pages 41-57 in: Forest Pathology: From Genes to Landscapes. J. Lundquist and R. Hamelin, eds. The American Phytopathological Society. St. Paul, MN, 2005. (2) G. I. McDonald et al. For. Pathol. 36:73, 2006. (3) T. J. White et al. Pages 315-322 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al. eds. Academic Press, San Diego, CA, 1990.

DNA from bird-dispersed seed and wind-disseminated pollen provides insights into postglacial colonization and population genetic structure of whitebark pine (Pinus albicaulis).

Uniparentally inherited mitochondrial (mt)DNA and chloroplast (cp)DNA microsatellites (cpSSRs) were used to examine population genetic structure and biogeographic patterns of bird-dispersed seed and wind-disseminated pollen of whitebark pine (Pinus albicaulis Engelm.). Sampling was conducted from 41 populations throughout the range of the species. Analyses provide evidence for an ancestral haplotype and two derived mtDNA haplotypes with distinct regional distributions. An abrupt contact zone between mtDNA haplotypes in the Cascade Range suggests postglacial biogeographic movements. Among three cpSSR loci, 42 haplotypes were detected within 28 cpSSR sample populations that were aggregated into six regions. Analysis of molecular variance (amova) was used to determine the hierarchical genetic structure of cpSSRs. amova and population pairwise comparisons (FST ) of cpSSR, and geographical distribution of mtDNA haplotypes provide insights into historical changes in biogeography. The genetic data suggest that whitebark pine has been intimately tied to climatic change and associated glaciation, which has led to range movements facilitated by seed dispersal by Clark's nutcracker (Nucifraga columbiana Wilson). The two hypotheses proposed to explain the genetic structure are: (i) a northward expansion into Canada and the northern Cascades in the early Holocene; and (ii) historical gene flow between Idaho and the Oregon Cascades when more continuous habitat existed in Central Oregon during the late Pleistocene. Genetic structure and insights gained from historical seed movements provide a basis on which to develop recovery plans for a species that is at risk from multiple threats.

Timing of breast milk HIV-1 transmission: a meta-analysis.

OBJECTIVE: To define the frequency and timing of breast milk transmission of HIV-1. DESIGN: Meta-analysis of data abstracted from published literature. SUBJECTS: Participants in prospective cohort studies of MTCT of HIV-1. Cohorts were separated on the basis of breast feeding duration. INTERVENTIONS: None. MAIN OUTCOME MEASURES: HIV-1 transmission rates. RESULTS: Two thousand three hundred and seventy five HIV-1 infected women and their infants, 499 of whom breast fed, the estimated risk of breast milk HIV-1 transmission was 16% (95% CI: 9, 22%). Among breastfeeding infants, forty seven per cent of HIV-1 infections were attributable to breast feeding. Breast milk transmission risk was 21% (95% CI: 10, 33%) in cohorts with mean/median duration of breast feeding > or = 3 months and 13% (95% CI: 4, 21%) in cohorts with median duration of breast feeding < 2 months. In a separate analysis of 702 infants with prolonged duration of breast feeding, the risk of late postnatal transmission (infection occurring later than three to six months of age) was four per cent (95% CI 2, 5%). CONCLUSIONS: This analysis suggests that breast milk transmission of HIV-1 is substantial and continues throughout the postnatal period. Early cessation of breast feeding at six months would avert some but not most infant HIV-1 infections due to breast feeding. While recently published studies showing some effectiveness of antiretrovirals early during the breast feeding period are encouraging, prevention of breast milk HIV-1 transmission needs to remain a high research priority.

Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study.

OBJECTIVES: To examine the relationship between use of oral contraceptive pills or depot medroxyprogesterone acetate and sexually transmitted disease acquisition. STUDY DESIGN: Prospective cohort included 948 Kenyan prostitutes. Multivariate Andersen-Gill proportional hazards models were constructed, adjusting for sexual behavioral and demographic variables. RESULTS: When compared with women who were using no contraception, users of oral contraceptive pills were at increased risk for acquisition of chlamydia (hazard ratio, 1.8; 95% confidence interval, 1.1-2.9) and vaginal candidiasis (hazard ratio, 1.5; 95% confidence interval, 1.2-1.9) and at decreased risk for bacterial vaginosis (hazard ratio, 0.8; 95% confidence interval, 0.7-1.0). Women using depot medroxyprogesterone acetate had significantly increased risk of chlamydia infection (hazard ratio, 1.6; 95% confidence interval, 1.1-2.4) and significantly decreased risk of bacterial vaginosis (hazard ratio, 0.7; 95% confidence interval, 0.5-0.8), trichomoniasis (hazard ratio, 0.6; 95% confidence interval, 0.4-1.0), and pelvic inflammatory disease (hazard ratio, 0.4; 95% confidence interval, 0.2-0.7). Consistent condom use was associated with significantly decreased risk of gonorrhea, chlamydia, genital ulcer disease, bacterial vaginosis, and pelvic inflammatory disease. CONCLUSIONS: The use of oral or injectable hormonal contraception altered susceptibility to sexually transmitted diseases, which may in turn influence transmission of human immunodeficiency virus type 1. Consistent condom use was protective with regards to sexually transmitted disease and should be encouraged for the prevention of sexually transmitted disease and human immunodeficiency virus type 1 among women who use hormonal contraception.

Evaluation of a low-dose nonoxynol-9 gel for the prevention of sexually transmitted diseases: a randomized clinical trial.

BACKGROUND: Low-dose nonoxynol-9 products have a potential advantage of reduced toxicity. However, little is known about their efficacy in reducing the incidence of sexually transmitted diseases (STDs). GOAL: To determine the effect that an intravaginal gel containing 52.5 mg of nonoxynol-9 has on the acquisition of STDs in a cohort of HIV-1-seronegative female sex workers in Mombasa, Kenya. STUDY DESIGN: A randomized double-blind placebo controlled trial was performed. RESULTS: In this study, 139 women were randomized to the nonoxynol-9 group and 139 to the placebo group. No significant differences were found between the two study groups in terms of safety outcomes and reported symptoms, except for a lower incidence of vaginal erythema in the nonoxynol-9 group. There was a significantly higher incidence of gonorrhea in the nonoxynol-9 group than in the placebo group. No significant differences were observed between the groups for acquisition of Candida, trichomonas, bacterial vaginosis, C trachomatis, syphilis, or HIV-1, although the statistical power to detect differences for some of these STDs was limited. CONCLUSIONS: In this randomized placebo-controlled trial of a low-dose nonoxynol-9 gel, a significantly higher incidence of gonorrhea was found in the nonoxynol-9 group, but no significant differences between the groups were found for Candida, trichomonas, bacterial vaginosis, C trachomatis, syphilis, or HIV-1.

Effect of breastfeeding on mortality among HIV-1 infected women: a randomised trial.

BACKGROUND: We have completed a randomised clinical trial of breastfeeding and formula feeding to identify the frequency of breastmilk transmission of HIV-1 to infants. However, we also analysed data from this trial to examine the effect of breastfeeding on maternal death rates during 2 years after delivery. We report our findings from this secondary analysis. METHODS: Pregnant women attending four Nairobi city council clinics were offered HIVtests. At about 32 weeks' gestation, 425 HIV-1 seropositive women were randomly allocated to either breastfeed or formula feed their infants. After delivery, mother-infant pairs were followed up monthly during the first year and quarterly during the second year until death, or 2 years after delivery, or end of study. FINDINGS: Mortality among mothers was higher in the breastfeeding group than in the formula group (18 vs 6 deaths, log rank test, p=0.009). The cumulative probability of maternal death at 24 months after delivery was 10.5% in the breastfeeding group and 3.8% in the formula group (p=0.02). The relative risk of death for breastfeeding mothers versus formula feeding mothers was 3.2 (95% CI 1.3-8.1, p=0.01). The attributable risk of maternal death due to breastfeeding was 69%. There was an association between maternal death and subsequent infant death, even after infant HIV-1 infection status was controlled for (relative risk 7.9, 95% CI 3.3-18.6, p<0.001). INTERPRETATION: Our findings suggest that breastfeeding by HIV-1 infected women might result in adverse outcomes for both mother and infant.

Correlates of mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission: association with maternal plasma HIV-1 RNA load, genital HIV-1 DNA shedding, and breast infections.

To determine the effects of plasma, genital, and breast milk human immunodeficiency virus type 1 (HIV-1) and breast infections on perinatal HIV-1 transmission, a nested case-control study was conducted within a randomized clinical trial of breast-feeding and formula feeding among HIV-1-seropositive mothers in Nairobi, Kenya. In analyses comparing 92 infected infants with 187 infants who were uninfected at 2 years, maternal viral RNA levels >43,000 copies/mL (cohort median) were associated with a 4-fold increase in risk of transmission (95% confidence interval [CI], 2.2-7.2). Maternal cervical HIV-1 DNA (odds ratio [OR], 2.4; 95% CI, 1.3-4.4), vaginal HIV-1 DNA (OR, 2.3; 95% CI, 1.1-4.7), and cervical or vaginal ulcers (OR, 2.7; 95% CI, 1.2-5.8) were significantly associated with infant infection, independent of plasma virus load. Breast-feeding (OR, 1.7; 95% CI, 1.0-2.9) and mastitis (relative risk [RR], 3.9; 95% CI, 1.2-12.7) were associated with increased transmission overall, and mastitis (RR, 21.8; 95% CI, 2.3-211.0) and breast abscess (RR, 51.6; 95% CI, 4.7-571.0) were associated with late transmission (occurring >2 months postpartum). Use of methods that decrease infant exposure to HIV-1 in maternal genital secretions or breast milk may enhance currently recommended perinatal HIV-1 interventions.

Trends in HIV-1 incidence in a cohort of prostitutes in Kenya: implications for HIV-1 vaccine efficacy trials.

BACKGROUND: Accurate predictions of HIV-1 incidence in potential study populations are essential for designing HIV-1 vaccine efficacy trials. Little information is available on the estimated incidence of HIV-1 in such populations, especially information on incidence over time and incidence while participating in risk-reduction programs. OBJECTIVES: To examine time trends in HIV-1 incidence in a vaccine preparedness cohort. DESIGN: Prospective cohort study of female prostitutes in Mombasa, Kenya. METHODS: HIV-1 incidence was determined using open and closed cohort designs. Generalized estimating equations were used to model HIV-1 and sexually transmitted disease (STD) incidence and sexual risk behaviors over time. RESULTS: When analyzed as a closed cohort, HIV-1 incidence declined 10-fold during 3 years of follow-up (from 17.4 to 1.7 cases/100 person-years; p <.001). More than 50% of the cases of HIV-1 occurred during the first 6 months after enrollment, and 73% during the first 12 months. When analyzed as an open cohort, HIV-1 incidence density fell during the first 4 calendar years, influenced by accumulation of lower risk participants and variations in study recruitment. Significant declines occurred in both STD incidence and high-risk sexual behaviors during follow-up. CONCLUSIONS: This study documents a dramatic decline in the risk of HIV-1 infection while participating in a prospective cohort, with most seroconversions occurring within 1 year of enrollment. Variations in HIV-1 incidence within high-risk populations should be anticipated during the design of vaccine trials.

Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons.

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.

Evaluation of performance of the Gen-Probe human immunodeficiency virus type 1 viral load assay using primary subtype A, C, and D isolates from Kenya.

Accurate and sensitive quantification of human immunodeficiency virus type 1 (HIV-1) RNA has been invaluable as a marker for disease prognosis and for clinical monitoring of HIV-1 disease. The first generation of commercially available HIV-1 RNA tests were optimized to detect the predominant HIV-1 subtype found in North America and Europe, subtype B. However, these tests are frequently suboptimal in detecting HIV-1 genetic forms or subtypes found in other parts of the world. The goal of the present study was to evaluate the performance of a new viral load assay with non-subtype B viruses. A transcription-mediated amplification method for detection and quantitation of diverse HIV-1 subtypes, called the Gen-Probe HIV-1 viral load assay, is under development. In this study we examined the performance of the Gen-Probe HIV-1 viral load assay relative to that of the commonly used commercial HIV-1 RNA assays using a panel of primary isolates from Kenya. For comparison, we included several subtype B cloned viruses, and we quantified each virus using an in-house quantitative-competitive reverse transcriptase PCR (QC-RT-PCR) method and gag(p24) antigen capture. The Gen-Probe HIV-1 viral load assay and a version of the Roche AMPLICOR HIV-1 MONITOR test (version 1.5) that was designed to detect a broader range of subtypes were both sensitive for the quantification of Kenyan primary isolates, which represented subtype A, C, and D viruses. The Gen-Probe HIV-1 viral load assay was more sensitive for the majority of viruses than the Roche AMPLICOR HIV-1 MONITOR test version 1.0, the Bayer Quantiplex HIV RNA 3.0 assay, or a QC-RT-PCR method in use in our laboratory, suggesting that it provides a useful method for quantifying HIV-1 RNAs from diverse parts of the world, including Africa.