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H Nina Kim,
Jing Wang,
James Hughes,
Robert Coombs,
Jorge Sanchez,
Stewart Reid,
Sinead Delany-Moretlwe,
Frances Cowan,
Jonathan Fuchs,
Susan H Eshleman,
Leila Khaki,
Moira A McMahon,
Robert F Siliciano,
Anna Wald,
Connie Celum
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ABSTRACT: We evaluated whether acyclovir suppression during human immunodeficiency virus type 1 (HIV-1) acquisition reduces HIV-1 set point, increases CD4 cell counts, and selects reverse-transcriptase mutations among 76 HIV-1 seroconverters identified in a placebo-controlled trial of twice-daily acyclovir (400 mg) for the prevention of HIV acquisition in herpes simplex virus type 2 (HSV-2)-seropositive persons (HIV Prevention Trials Network study 039). We found no significant difference in plasma HIV-1 RNA levels (P =.30) or CD4 cell counts (P =.85) between the acyclovir and placebo recipients. V75I and other mutations in HIV-1 reverse transcriptase reported from in vitro acyclovir studies were not observed. In conclusion, acyclovir suppression during HIV-1 seroconversion and the subsequent 6 months does not affect HIV-1 set point.
The Journal of Infectious Diseases 09/2010; 202(5):734-8. · 6.41 Impact Factor
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ABSTRACT: Vaccine recommendations for those with HIV require continual updating as additional research becomes available. Timing of vaccinations among HIV-infected individuals is a key area of uncertainty. This is particularly true for those who may soon initiate highly active antiretroviral therapy (HAART) because immune reconstitution due to HAART often improves responses to vaccines. However, risks of delaying vaccination include that the patient may be exposed to the pathogen or lost to follow-up before vaccination. We review recent studies on the timing of routine vaccination of HIV-infected individuals.
Current HIV/AIDS Reports 06/2009; 6(2):93-9.
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ABSTRACT: Protective response rates to hepatitis B (HB) vaccination have been reported as low as 18-62% in HIV-infected persons. The relative importance of various predictors for this poor response has not been fully characterized. In this retrospective cohort study, we examined the relationship between clinical characteristics and vaccine non-response (HB surface antibody <10 IU/L) among patients attending an urban HIV clinic. Among the 97 patients who met the inclusion criteria, 43 (44%) developed a protective antibody response. In multivariate analyses, age >40 years (odds ratio [OR] 3.03 [95% confidence interval [CI], 1.14-8.06]; P = 0.026) and alcohol abuse (OR 4.92 [95% CI, 1.72-20.89]; P = 0.007) were independent predictors of failure to develop vaccine response. In addition, CD4 nadir <200 (OR 7.24 [95% CI, 1.91-27.41]; P = 0.004), rather than CD4 current to vaccination, remained a strong independent risk factor. Patients with HIV viral suppression on highly active antiretroviral therapy had a significantly lower rate of vaccine failure (OR 0.31 [95% CI, 0.11-0.91]; P = 0.033), after adjusting for these other covariates. Our findings underscore the importance of confirming seroconversion after HB vaccination in HIV-infected patients and initiating vaccination early in the course of HIV infection.
International Journal of STD & AIDS 10/2008; 19(9):600-4. · 1.09 Impact Factor
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ABSTRACT: The benefit of suppressive antiviral therapy for reducing the risk of herpes simplex virus (HSV)-2 transmission to sex partners may be enhanced if persons at high risk for transmission can be identified.
To determine whether frequency of genital herpes recurrences is associated with increased risk of HSV-2 transmission.
Analysis of recurrence frequency and shedding frequency (subset) among participants in a randomized controlled trial of valacyclovir 500 mg qd versus placebo for reducing the risk of HSV-2 transmission.
Overall, 1484 monogamous HSV-2-serodiscordant couples participated and 41 HSV-2 transmissions occurred during the 8-month trial; 40 were able to provide a history of recurrence frequency. The rate of recurrences per year before study entry did not differ between source partners who transmitted and those who did not, 4.8 versus 5.1, respectively. Similarly, the mean frequency of recurrences observed during the study also did not differ among those who transmitted versus those who did not for placebo recipients (4.4 vs. 4.8) or valacyclovir recipients (1.4 vs. 1.3). Among the 40 source partners who transmitted HSV-2, 8 of 27 placebo recipients and 7 of 13 valacyclovir recipients had no recurrences during the study.
Clinical assessment of HSV-2 disease severity as defined by the frequency of genital herpes recurrences does not predict the risk of transmission to sexual partners. Though patients with frequent recurrences are most likely to benefit clinically from suppressive therapy, frequency of recurrences is not helpful in identifying persons who are most likely to transmit HSV-2.
Sex Transm Dis 03/2008; 35(2):124-8. · 2.87 Impact Factor
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ABSTRACT: We describe repeated episodes of hepatitis C (HCV) activation associated with initiation of highly active antiretroviral therapy (HAART) in two HIV/HCV coinfected individuals with undetectable serum HCV RNA. Both patients developed high HCV viremia (>1 million IU/mL) and elevations in aminotransferases >10 times upper limit of normal) within 4 months of starting HAART. This is the first report of clinically significant HCV activation in HCV-seropositive patients with initially undetectable HCV viremia. These observations suggest that flares of hepatitis C in the setting of the immune reconstitution inflammatory syndrome can occur even in those patients who have undetectable serum HCV levels prior to HAART initiation.
AIDS PATIENT CARE and STDs 11/2007; 21(10):718-23. · 2.41 Impact Factor
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Sex Transm Dis 04/2007; 34(3):139-40. · 2.87 Impact Factor
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ABSTRACT: Combination antiretroviral therapy (ART) has transformed the care of individuals who have HIV infection. Effective ART has resulted in dramatic reductions in mortality, hospitalization rates, and the development of AIDS-defining illnesses. This article discusses the variety of agents that can comprise an effective ART regimen, focusing on the basic principles of ART, the indications for initiating ART in treatment-naive individuals who have established HIV infection, and the challenges associated with the use of antiretroviral medications.
Dermatologic Clinics 11/2006; 24(4):537-47, vii. · 2.16 Impact Factor
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ABSTRACT: Previous studies using viral cultures rarely reported herpes simplex virus type 2 (HSV-2) isolation from the mouth. We sought to characterize oral HSV-2 shedding as detected by HSV DNA polymerase chain reaction among HSV-2-seropositive men.
Participants collected daily swabs from oral and anogenital areas for HSV detection with a quantitative polymerase chain reaction assay.
A total of 109 HSV-2-seropositive men (59 of whom were human immunodeficiency virus [HIV] negative, and 50 of whom were HIV positive) were sampled for a median of 64 consecutive days. Forty-four (40.4%) had HSV-2 detected from oral swabs on at least 1 day. Oral HSV-2 was detected on 148 (2.3%) of 6,422 days, genital HSV-2 was detected on 1,110 (17%) of 6,505 days, oral HSV-1 was detected on 220 (5.5%) of 4,018 days, and genital HSV-1 was detected on 88 (2.2%) of 4,073 days. Oral HSV-2 shedding was never associated with an oral lesion, but it was often concurrent with genital HSV-2 shedding. Both oral and genital HSV-2 were detected on 90 (61%) of 148 days with oral HSV-2 shedding. Oral HSV-2 shedding occurred on 90 (8.2%) of 1,110 days with genital HSV-2 shedding, versus 58 (1.1%) of 5,316 days without genital HSV-2 shedding (P<.001). The HIV-positive men shed HSV-2 orally more frequently than did the HIV-negative men (odds ratio, 2.7 [95% confidence interval, 1.1-7.1]).
Oral HSV-2 reactivation was common (especially among HIV-positive men), was always asymptomatic, and often occurred on days of genital HSV-2 reactivation.
The Journal of Infectious Diseases 08/2006; 194(4):420-7. · 6.41 Impact Factor
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ABSTRACT: Potential strategies to prevent neonatal herpes include herpes simplex virus (HSV) serologic testing and counseling of pregnant women and rapid HSV polymerase chain reaction (PCR) testing of maternal genital secretions at delivery. The cost-effectiveness of these interventions would be improved if high-risk pregnancies could be easily identified for targeted testing.
Washington State birth certificate data for all singleton live births from 1987 through 2002 were linked with infant death and hospital discharge data for birth and subsequent hospitalizations in a population-based case-control study of risk factors for neonatal herpes. A case was defined as an infant with a discharge diagnosis of HSV infection (International Classification of Diseases 9th edition [ICD-9] code 054.X) from birth admission or readmission within 30 days of life. Five controls per case were frequency matched to cases by year of birth.
Ninety-one neonatal HSV cases were identified (8.4/100,000 live births). Risk factors for infection included maternal age younger than 25 years (adjusted odds ratio [aOR] = 1.9, 95% CI 1.1-3.3) and paternal age younger than 20 years or unknown (aOR = 1.7, 95% CI 0.7-3.7). Testing couples with either risk factor would require testing 36% of couples and could potentially prevent up to 60% of cases. Maternal history of genital herpes, fever during labor, and premature rupture of membranes were also associated with neonatal disease; using all risk factors identifiable at delivery would require screening 60% of pregnancies and identifying 84% of cases.
Targeted HSV testing would miss a substantial proportion of neonatal herpes.
American journal of obstetrics and gynecology 03/2006; 194(2):408-14. · 3.28 Impact Factor
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ABSTRACT: Instead of preventing infection, most HIV-1 vaccines in clinical trials are directed at inducing cytotoxic HIV-1-specific T cell (CTL) responses which may control viral replication and subsequently modify the clinical course of HIV-1 infection. Thus, vaccine efficacy trial designs must follow participants who become HIV-infected and monitor the course of HIV-1 infection, in order to assess the effect of vaccination on HIV-1 disease progression. This post-infection evaluation will assess time to reach specific CD4 and viral load thresholds as well as time to initiation of antiretroviral therapy. This paper discusses current literature and guidelines on the initiation of highly active antiretroviral therapy (HAART) for persons who become HIV-infected during HIV-1 vaccine trials, focusing both on acute and early HIV-1 infection, since participants in HIV-1 vaccine and other prevention trials will typically be identified within 3-6 months after HIV-1 acquisition. A standardized HAART protocol for HIV-1 vaccine efficacy trial participants who become HIV-infected is essential to the evaluation of CTL-based HIV-1 vaccines on the natural history of HIV-1 infection.
Vaccine 02/2006; 24(4):532-9. · 3.77 Impact Factor
