R. Scott McClelland

Outcome of Staphylococcus aureus Bacteremia According to Compliance with Recommendations of Infectious Diseases Specialists: Experience with 244 Patients

To determine whether recommendations of infectious diseases specialists affect outcome for patients, we evaluated 244 hospitalized patients with Staphylococcus aureus bacteremia. We offered our management recommendations to each patients physicians and then assessed the clinical outcome for both patients for whom our consultative advice was followed and those for whom our advice was not heeded. All patients were followed up for 12 weeks after their first positive blood culture. Our management advice was followed for 112 patients (45.9%) and partially or completely ignored for 132 patients (54.1%). Patients for whom our recommendations were followed were more likely to be cured of their S. aureus infection and less likely to relapse (P < .01), despite having significantly more metastatic infections (P < .01) at the outset of therapy, than were those for whom our recommendations were not followed. Failure to follow recommendations to remove an infected intravascular device was the most important risk for treatment failure. After controlling for other factors, logistic regression analysis revealed that patients whose intravascular device was not removed were 6.5 times more likely to relapse or die of their infection than were those whose device was removed. Our findings suggest that patient-specific management advice by infectious diseases consultants can improve the clinical outcome for patients with S. aureus bacteremia.

Infection with Trichomonas vaginalis Increases the Risk of HIV-1 Acquisition

We conducted a prospective study among women in Mombasa, Kenya, to determine whether Trichomonas vaginalis infection was associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) infection. At monthly follow-up visits, laboratory screening for HIV-1 and genital tract infections was conducted. Among 1335 HIV-1-seronegative women monitored for a median of 566 days, there were 806 incident T. vaginalis infections (23.6/100 person-years), and 265 women seroconverted to HIV-1 (7.7/100 person-years). Trichomoniasis was associated with a 1.52-fold (95% confidence interval, 1.04-2.24-fold) increased risk of HIV-1 acquisition after adjustment for potential confounding factors. Treatment and prevention of T. vaginalis infection could reduce HIV-1 risk in women.

HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 Loads

We investigated the effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression among 145 Kenyan women followed from the time of HIV-1 acquisition. Compared with those infected with subtype A, women infected with subtype D had higher mortality (hazard ratio, 2.3 [95% confidence interval, 1.0-5.6]) and a faster rate of CD4 cell count decline (P=.003). The mortality risk persisted after adjustment for plasma HIV-1 load. There were no differences in plasma viral load by HIV-1 subtype during follow-up. HIV-1 subtype D infection is associated with a >2-fold higher risk of death than subtype A infection, in spite of similar plasma HIV-1 loads.

The Effect of Treatment of Vaginal Infections on Shedding of Human Immunodeficiency Virus Type 1

To assess the effect of treatment of vaginal infections on vaginal shedding of cell-free human immunodeficiency virus type 1 (HIV-1) and HIV-1-infected cells, HIV-1-seropositive women were examined before and after treatment of Candida vulvovaginitis, Trichomonas vaginitis, and bacterial vaginosis. For Candida (n=98), vaginal HIV-1 RNA decreased from 3.36 to 2.86 log(10) copies/swab (P<.001), as did the prevalence of HIV-1 DNA (36% to 17%; odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.5). For Trichomonas vaginitis (n=55), HIV-1 RNA decreased from 3.67 to 3.05 log(10) copies/swab (P<.001), but the prevalence of HIV-1 DNA remained unchanged (22%-25%; OR, 0.8; 95% CI, 0.3-2.2). For bacterial vaginosis (n=73), neither the shedding of HIV-1 RNA (from 3.11 to 2.90 log(10) copies/swab; P=.14) nor the prevalence of DNA (from 21% to 23%; OR, 0.8; 95% CI, 0.3-2.0) changed. Vaginal HIV-1 decreased 3.2- and 4.2-fold after treating Candida and Trichomonas, respectively. These data suggest that HIV-1 transmission intervention strategies that incorporate diagnosis and treatment of these prevalent infections warrant evaluation.

HIV-1 infection in high risk men who have sex with men in Mombasa, Kenya

Background:The role of homosexuality and anal sex practices in the African HIV -1 epidemic is not well described. We aimed to assess the risk factors for prevalent HIV-1 infection among men who have sex with men (MSM) to guide HIV-1 prevention efforts. Methods:Socio-behavioural characteristics, signs and symptoms of sexually transmitted diseases (STD), and serological evidence of HIV-1 were determined for 285 MSM at enrolment into a vaccine preparedness cohort study. We used multivariate logistic regression to assess risk factors for prevalent HIV-1 infection. Results:HIV-1 prevalence was 43.0% [49/114, 95% confidence interval (CI), 34–52%] for men who reported sex with men exclusively (MSME), and 12.3% (21/171, 95% CI, 7–17%) for men who reported sex with both men and women (MSMW). Eighty-six (75%) MSME and 69 (40%) MSMW reported recent receptive anal sex. Among 174 MSM sexually active in the last week, 44% reported no use of condoms with casual partners. In the previous 3 months, 210 MSM (74%) reported payment for sex, and most clients (93%) were local residents. Prevalent HIV-1 infection was associated with recent receptive anal sex [odds ratio (OR), 6.1; 95% CI, 2.4–16], exclusive sex with men (OR, 6.3; 95% CI, 2.3–17), and increasing age (OR, 1.1 per year; 95% CI, 1.04–1.12). Only four MSM reported injecting drug use. Conclusions:The high prevalence of HIV-1 in Kenyan MSM is probably attributable to unprotected receptive anal sex. There is an urgent need for HIV-1 prevention programmes to deliver targeted risk-reduction interventions and STD services to MSM in Kenya.

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

ObjectiveTo determine whether cervical mucosal shedding of HIV-1 RNA and HIV-1 infected cells decreases following successful treatment of cervicitis. DesignProspective interventional study. SettingSexually Transmitted Infections Clinic, Coast Provincial General Hospital, Mombasa, Kenya. ParticipantsThirty-six HIV-1 seropositive women with cervicitis: 16 with Neisseria gonorrhoeae, seven with Chlamydia trachomatis, and 13 with non-specific cervicitis. InterventionsTreatment of cervicitis. Main outcome measuresLevels of total (cell-free and cell-associated) HIV-1 RNA and presence of HIV-1 DNA (a marker for infected cells) in cervical secretions before and after resolution of cervicitis. ResultsAfter treatment of cervicitis, the median HIV-1 RNA concentration in cervical secretions was reduced from 4.05 to 3.24 log10 copies/swab (P = 0.001). Significant decreases in cervical HIV-1 RNA occurred in the subgroups with N. gonorrhoeae (3.94 to 3.28 log10 copies/swab;P = 0.02) and C. trachomatis (4.21 to 3.19 log10 copies/swab;P = 0.02). Overall, the prevalence of HIV-1 infected cells in cervical secretions also decreased after treatment, from 67% to 42% (odds ratio, 2.8; 95% confidence interval, 1.3–6.0;P = 0.009). Detection of infected cells was associated with higher mean HIV-1 RNA levels (4.04 versus 2.99 log10copies/swab;P < 0.0001). ConclusionsEffective treatment of cervicitis resulted in significant decreases in shedding of HIV-1 virus and infected cells in cervical secretions. Treatment of sexually transmitted diseases may be an important means of decreasing the infectivity of HIV-1 seropositive women by reducing exposure to HIV-1 in genital secretions.

Infective Endocarditis Due to Staphylococcus aureus: 59 Prospectively Identified Cases with Follow-up

Fifty-nine consecutive patients with definite Staphylococcus aureus infective endocarditis (IE) by the Duke criteria were prospectively identified at our hospital over a 3-year period. Twenty-seven (45.8%) of the 59 patients had hospital-acquired S. aureus bacteremia. The presumed source of infection was an intravascular device in 50.8% of patients. Transthoracic echocardiography (TTE) revealed evidence of IE in 20 patients (33.9%), whereas transesophageal echocardiography (TEE) revealed evidence of IE in 48 patients (81.4%). The outcome for patients was strongly associated with echocardiographic findings: 13 (68.4%) of 19 patients with vegetations visualized by TTE had an embolic event or died of their infection vs. five (16.7%) of 30 patients whose vegetations were visualized only by TEE (P < .01). Most patients with S. aureus IE developed their infection as a consequence of a nosocomial or intravascular device-related infection. TEE established the diagnosis of S. aureus IE in many instances when TTE was nondiagnostic. Visualization of vegetations by TTE may provide prognostic information for patients with S. aureus IE.

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis:

In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.

Hormonal Contraceptive Use, Herpes Simplex Virus Infection, and Risk of HIV-1 Acquisition Among Kenyan Women

Background:Studies of the effect of hormonal contraceptive use on the risk of HIV-1 acquisition have generated conflicting results. A recent study from Uganda and Zimbabwe found that women using hormonal contraception were at increased risk for HIV-1 if they were seronegative for herpes simplex virus type 2 (HSV-2), but not if they were HSV-2 seropositive. Objective:To explore the effect of HSV-2 infection on the relationship between hormonal contraception and HIV-1 in a high-risk population. Hormonal contraception has previously been associated with increased HIV-1 risk in this population. Methods:Data were from a prospective cohort study of 1206 HIV-1 seronegative sex workers from Mombasa, Kenya who were followed monthly. Multivariate Cox proportional hazards analyses were used to adjust for demographic and behavioral measures and incident sexually transmitted diseases. Results:Two hundred and thirty-three women acquired HIV-1 (8.7/100 person-years). HSV-2 prevalence (81%) and incidence (25.4/100 person-years) were high. In multivariate analysis, including adjustment for HSV-2, HIV-1 acquisition was associated with use of oral contraceptive pills [adjusted hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.00–2.13] and depot medroxyprogesterone acetate (adjusted HR, 1.73; 95% CI, 1.28–2.34). The effect of contraception on HIV-1 susceptibility did not differ significantly between HSV-2 seronegative versus seropositive women. HSV-2 infection was associated with elevated HIV-1 risk (adjusted HR, 3.58; 95% CI, 1.64–7.82). Conclusions:In this group of high-risk African women, hormonal contraception and HSV-2 infection were both associated with increased risk for HIV-1 acquisition. HIV-1 risk associated with hormonal contraceptive use was not related to HSV-2 serostatus.

Breadth of Neutralizing Antibody Response to Human Immunodeficiency Virus Type 1 Is Affected by Factors Early in Infection but Does Not Influence Disease Progression

ABSTRACT The determinants of a broad neutralizing antibody (NAb) response and its effect on human immunodeficiency virus type 1 (HIV-1) disease progression are not well defined, partly because most prior studies of a broad NAb response were cross-sectional. We examined correlates of NAb response breadth among 70 HIV-infected, antiretroviral-naïve Kenyan women from a longitudinal seroincident cohort. NAb response breadth was measured 5 years after infection against five subtype A viruses and one subtype B virus. Greater NAb response breadth was associated with a higher viral load set point and greater HIV-1 env diversity early in infection. However, greater NAb response breadth was not associated with a delayed time to a CD4+ T-cell count of <200, antiretroviral therapy, or death. Thus, a broad NAb response results from a high level of antigenic stimulation early in infection, which likely accounts for prior observations that greater NAb response breadth is associated with a higher viral load later in infection.