Biomedical subjects

Connie L Celum

Publications and source records attributed to Connie L Celum.

At least 19 recordsLinked to original sources

PubMed2025

HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data.

BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.

HIV Infections↗

PubMed2006

Association of herpes simplex virus type 2 infection and syphilis with human immunodeficiency virus infection among men who have sex with men in Peru.

BACKGROUND: We evaluated associations between human immunodeficiency virus (HIV) infection, herpes simplex virus type 2 (HSV-2) infection, and syphilis among men who have sex with men (MSM) in Peru. METHODS: A surveillance survey of 3280 MSM was conducted; sexual behavior was assessed with a structured computer-assisted self-interview, and serum antibody testing was performed for HIV, HSV-2, and Treponema pallidum. RESULTS: HIV, HSV-2, and syphilis seroprevalences of 13.9%, 46.3%, and 13.4% were detected, respectively. HSV-2 seroprevalence was twice as high in HIV-infected subjects (80.5%) than it was in HIV-uninfected subjects (40.8%) (P < .01), and HSV-2 seropositivity (adjusted odds ratio [AOR], 5.66) was found to be strongly associated with HIV infection. In addition, homosexual self-definition (AOR, 3.12), exchange of sex for money (AOR, 1.61), unprotected sex (no condom) (AOR, 2.81), history of sex work (AOR, 1.89), oral receptive sex (AOR, 1.43), and cocaine use before/during sex (AOR, 2.53) within the preceding 6 months, as well as such sexually transmitted infections (STIs) and STI syndromes as proctitis (AOR, 2.80), genital ulcer disease (GUD) (AOR, 2.06), prior syphilis (AOR, 2.64), genital warts (AOR, 1.70), and self-reported STIs within the preceding 6 months (AOR, 1.61), were also found to be significant predictors of HIV infection. CONCLUSIONS: We found a strong association between HSV-2 seropositivity and HIV infection. Intervention measures against GUD due to HSV-2 infection and syphilis, such as routine testing, early detection, HSV-2 suppressive treatment, and condom distribution, need to be enhanced as part of STI prevention strategies at a national level to effectively reduce HIV infection among MSM in Peru.

Adolescent↗

PubMed2006

Partner-specific sexual behavioral differences between phase 3 HIV vaccine efficacy trial participants and controls: Project VISION.

OBJECTIVE: To assess and compare sexual behaviors using partner-specific data between HIV-negative men who have sex with men (MSM) recruited for an HIV vaccine efficacy trial and a control group. METHODS: HIV-negative MSM from an HIV vaccine trial (n = 525) and controls (n = 732) were recruited by similar strategies and interviewed about behaviors with the 3 most recent partners in the past 6 months, obtained by audio computer-assisted self-interview (A-CASI). RESULTS: Vaccine trial participants were more likely than controls to report an HIV-positive partner (24.7% and 14.1%, respectively) or an HIV-positive primary partner (16.1% and 6.8%, respectively) and were less likely to report occasional or single-time partners of unknown HIV status (51.6% and 63.2%, respectively; P < 0.05 for each comparison). Vaccine trial participants more often reported receptive unprotected anal intercourse (UAI) during their last sexual encounter with an HIV-positive partner (adjusted odds ratio [OR] = 2.7, 95% confidence interval [CI]: 1.0 to 7.9). Most believed their HIV-positive partners were receiving antiretroviral treatment (ART), however, and after adjustment for perceived ART use, the association between vaccine study participation and receptive UAI with an HIV-positive partner was not significant. CONCLUSIONS: High-risk sexual behavior was reported by many VAX004 participants and controls. Differences between vaccine trial and control participants in the highest risk per contact behavior, receptive UAI with HIV-positive partners, was partly accounted for by perceived ART use. Partner level data are useful in refining risk assessment, which is important in the evaluation of HIV vaccine and other prevention trials.

AIDS Vaccines↗

PubMed2005

Antiretroviral therapy for HIV-1 vaccine efficacy trial participants who seroconvert.

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.

AIDS Vaccines↗

PubMed2005

Sexual risk, nitrite inhalant use, and lack of circumcision associated with HIV seroconversion in men who have sex with men in the United States.

Men who have sex with men (MSM) continue to account for the largest number of new HIV infections in the United States, but limited data exist on independent risk factors for infection beyond the early 1990s. The HIV Network for Prevention Trials Vaccine Preparedness Study enrolled 3257 MSM in 6 US cities from 1995 to 1997. HIV seroincidence was 1.55 per 100 person-years (95% confidence interval: 1.23-1.95) over 18 months of follow-up. On multi-variable analysis using time-dependent covariates, independent risk factors for HIV seroconversion were increased number of reported HIV-negative male sex partners (adjusted odds ratio (AOR) = 1.14 per partner, population attributable risk (PAR) = 28%), nitrite inhalant use (AOR = 2.2, PAR = 28%), unprotected receptive anal sex with an HIV unknown serostatus partner (AOR = 2.7, PAR = 15%) or HIV-positive partner (AOR = 3.4, PAR = 12%), protected receptive anal sex with an HIV-positive partner (AOR = 2.2, PAR = 11%), lack of circumcision (AOR = 2.0, PAR = 10%), and receptive oral sex to ejaculation with an HIV-positive partner (AOR = 3.8, PAR = 7%). Having a large number of male sex partners, nitrite inhalant use, and engaging in receptive anal sex explained the majority of infections in this cohort and should be targeted in prevention strategies for MSM.

Administration, Inhalation↗

PubMed2005

Potential effect of HIV type 1 antiretroviral and herpes simplex virus type 2 antiviral therapy on transmission and acquisition of HIV type 1 infection.

Biological strategies for interrupting transmission of human immunodeficiency virus (HIV) type 1 should be directed at reducing infectiousness of and susceptibility to HIV-1. Potential antiretroviral interventions include reducing the likelihood of transmission of HIV-1 by reducing HIV-1 load in the blood and genital tract of HIV-1--infected person, prophylaxis after high-risk exposure, and pre-exposure prophylaxis for very high risk populations. Antiviral treatment of herpes simplex virus (HSV) type 2, the most common cause of genital ulcers, should be evaluated as a strategy for HIV-1 infection prevention by reducing infectiousness of and susceptibility to HIV-1, on the basis of biological and epidemiological data indicating that HSV-2 facilitates transmission and acquisition of HIV-1. The rationale for antiretroviral and HSV-2-specific interventions and studies to test these strategies are described.

Anti-HIV Agents↗

PubMed2004

Breakthrough infections during phase 1 and 2 prime-boost HIV-1 vaccine trials with canarypox vectors (ALVAC) and booster dose of recombinant gp120 or gp160.

Candidate human immunodeficiency virus (HIV)-1 vaccines that elicit cytotoxic T lymphocytes may modulate HIV infection, requiring a prototype evaluation to assess participants who become infected with HIV. Of 1497 participants in canarypox HIV-1 vaccine prime-boost trials, 28 (1.9%) acquired HIV-1 infection after vaccination. Median plasma HIV-1 RNA levels (vaccinees, 4.78 log10 copies/mL; placebo recipients, 4.27 log10 copies/mL) and CD4 cell counts (vaccinees, 552 cells/mm3; placebo recipients, 657 cells/mm3) before administration of antiretroviral therapy (ART) and time to a composite end point (plasma HIV-1 RNA level >55,000 copies/mL, CD4 cell count <350 cells/mm3, or initiation of ART) did not differ significantly between vaccinees and placebo recipients (P =.4, P =.1, and P =.7, respectively). Persons who acquire HIV-1 infection while enrolled in HIV-1 vaccine trials can be successfully followed after infection, to determine whether vaccines alter the course of HIV-1 infection.

AIDS Vaccines↗

PubMed2004

Higher concentration of HIV RNA in rectal mucosa secretions than in blood and seminal plasma, among men who have sex with men, independent of antiretroviral therapy.

High levels of human immunodeficiency virus (HIV) in rectal secretions and semen likely increase the risk of HIV transmission. HIV-infected men who have sex with men made 2-3 study visits, over 4 weeks, to assess rectal, seminal, and plasma levels of HIV RNA. Mixed-effects models estimated the effect of factors on HIV shedding. Twenty-seven (42%) of 64 men were receiving antiretroviral therapy (ART); regardless of ART use, median HIV RNA levels were higher in rectal secretions (4.96 log(10) copies/mL) than in blood plasma (4.24 log(10) copies/mL) or seminal plasma (3.55 log(10) copies/mL; P<.05, each comparison). ART was associated with a 1.3-log(10) reduction in rectal HIV RNA in a model without plasma HIV RNA; with and without plasma RNA in models, ART accounted for a >1-log(10) decrease in seminal HIV RNA levels. Thus, controlling for plasma HIV RNA, ART had an independent effect on seminal, but not rectal, HIV levels.

Adult↗

PubMed2004

The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics.

Increasing evidence demonstrates a substantial link between the epidemics of sexually transmitted HIV-1 and herpes simplex virus (HSV)-2 infection. More than 30 epidemiologic studies have demonstrated that prevalent HSV-2 is associated with a 2- to 4-fold increased risk of HIV-1 acquisition. Per-sexual contact transmission rates among couples from Rakai, Uganda indicate that at all levels of plasma HIV-1 RNA in the source partner, HSV-2-seropositive HIV-1-susceptible persons have a 5-fold greater risk of acquiring HIV-1 compared with HSV-2-negative persons. In vitro and in vivo studies suggest that mucosal HIV-1 shedding is more frequent and in greater amounts during mucocutaneous HSV-2 replication, including subclinical mucosal reactivations. Most HIV-1-infected persons are coinfected with HSV-2, and most experience frequent subclinical and clinical reactivations of HSV-2. Subclinical HSV reactivation elevates serum HIV-1 RNA levels, and daily therapy with acyclovir appears to reduce plasma HIV-1 RNA. These data show that greater attention to the diagnosis and treatment of HSV-2 among HIV-1-infected persons is warranted, especially those who continue to be sexually active, those not on antiretroviral therapy, or those whose disease is not well suppressed by antiretrovirals.

Acyclovir↗

PubMed2004

The interaction between herpes simplex virus and human immunodeficiency virus.

Many studies indicate that herpes simplex virus (HSV) seropositivity increases the risk of acquiring HIV, with fewer studies also indicating that HSV-2 infection increases the risk of transmitting HIV. In a recent meta-analysis, HSV-2 infection increased the risk of HIV-acquisition two-fold. This increased risk may occur by HSV-2 reactivation disrupting the epithelial barrier and recruiting activated CD4 cells, which are target cells for HIV infection, into the lesion. In vivo and in vitro studies assessing the effect of HSV-2 on HIV transmission demonstrate that HIV-infected CD4 cells are recruited to HSV-infected lesions and that HSV regulatory proteins (ICP0, ICP4, VP16) may upregulate HIV replication, thus increasing the frequency and titre of mucosal HIV shedding. This may occur during both clinical and asymptomatic HSV reactivation. Plausibly, antiherpetic therapy could reduce HIV transmission by decreasing HIV plasma load and/or mucosal HIV shedding, but a proof-of-concept trial is needed to demonstrate this. It also appears that individuals co-infected with HIV and HSV-2 have more frequent HSV recurrences than individuals infected with HSV-2 alone. There is a strong correlation between decreasing CD4 count and increasing rates of HSV reactivation, suggesting that reactivation is linked to immunosuppression. The IHMF recommends that individuals with HIV should be serologically tested for HSV-2. HSV-2 infection should be targeted as a modifiable risk factor for HIV acquisition by testing, counselling and preventing acquisition through behavioural interventions, treatment and antiviral suppression.

HIV↗

PubMed2003

Factors associated with oropharyngeal human immunodeficiency virus shedding.

Orogenital transmission of human immunodeficiency virus (HIV) is considered to be inefficient, and infectious HIV is rarely detected in saliva. To evaluate the posterior oropharynx as a source of HIV shedding, we studied 64 HIV-infected men who have sex with men in Seattle, Washington, and Lima, Peru. In multivariate analysis, receipt of antiretroviral therapy, higher CD4 cell count, and history of tonsillectomy were predictors of lower pharyngeal HIV RNA levels.

Adult↗

PubMed2003

Safety and acceptability of the Reality condom for anal sex among men who have sex with men.

OBJECTIVES: To assess safety and acceptability of Reality condoms for anal sex among men who have sex with men. METHODS: Crossover study among HIV-seroconcordant (33 HIV-negative and 5 HIV-positive) monogamous male couples, randomized to latex male and Reality condom use with anal sex. RESULTS: Slippage with removal was reported more frequently with Reality than male latex condoms [odds ratio (OR), 2.7; 95% confidence interval (CI), 1.2-5.8 for receptive partners and OR, 34.1; 95% CI, 13.8-84.1 for insertive partners]. Receptive partners more frequently reported pain or discomfort (OR, 5.0; 95% CI, 2.6-9.4) and rectal bleeding (OR, 1.9; 95% CI, 0.9-4.1) with Reality condoms than male condoms. Over 20% reported willingness to use the Reality condom in the future with a partner of unknown HIV status; willingness was associated with past problems with male condoms and no problems with Reality condoms among receptive partners, and with past use of Reality condoms and HIV seropositivity among insertive partners. CONCLUSIONS: Men reported more frequent problems with Reality condoms than male latex condoms used for anal intercourse, particularly slippage, discomfort, and rectal bleeding. Design modifications, training, and research on the clinical significance of safety outcomes are needed for use of Reality condoms with anal sex.

Adult↗

PubMed2003

Overcoming barriers to HIV testing: preferences for new strategies among clients of a needle exchange, a sexually transmitted disease clinic, and sex venues for men who have sex with men.

OBJECTIVE: To determine strategies to overcome barriers to HIV testing among persons at risk. METHODS: We developed a survey that elicited testing motivators, barriers, and preferences for new strategies among 460 participants at a needle exchange, three sex venues for men who have sex with men, and a sexually transmitted disease clinic. RESULTS: Barriers to testing included factors influenced by individual concern (fear and discrimination); by programs, policies, and laws (named reporting and inability to afford treatment); and by counseling and testing strategies (dislike of counseling, anxiety waiting for results, and venipuncture). The largest proportions of participants preferred rapid testing strategies, including clinic-based testing (27%) and home self-testing (20%); roughly equal proportions preferred oral fluid testing (18%), urine testing (17%), and standard blood testing (17%). One percent preferred home specimen collection. Participants who had never tested before were significantly more likely to prefer home self-testing compared with other strategies. Blacks were significantly more likely to prefer urine testing. CONCLUSIONS: Strategies for improving acceptance of HIV counseling and testing include information about access to anonymous testing and early treatment. Expanding options for rapid testing, urine testing, and home self-testing; providing alternatives to venipuncture; making pretest counseling optional; and allowing telephone results disclosure may encourage more persons to learn their HIV status.

Adult↗

PubMed2003

Herpes simplex virus type 2 infection as a risk factor for human immunodeficiency virus acquisition in men who have sex with men.

The association of human immunodeficiency virus (HIV) acquisition with herpes simplex virus type 2 (HSV-2) was assessed among men who have sex with men (MSM) in a nested case-control study of 116 case subjects who seroconverted to HIV during follow-up and 342 control subjects who remained HIV seronegative, frequency-matched by follow-up duration and report of HIV-infected sex partner and unprotected anal sex. The baseline HSV-2 seroprevalence was higher among case (46%) than control (34%) subjects (P=.03); the HSV-2 seroincidence was 7% versus 4% (P=.3). Only 15% of HSV-2-infected MSM reported herpes outbreaks in the past year. HIV acquisition was associated with prior HSV-2 infection (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.9), reporting >12 sex partners (OR, 2.9; 95% CI, 1.4-6.3), and reporting fewer herpes outbreaks in the past year (OR, 0.3; 95% CI, 0.1-0.8). HSV-2 increases the risk of HIV acquisition, independent of recognized herpes lesions and behaviors reflecting potential HIV exposure. HSV-2 suppression with antiviral therapy should be evaluated as an HIV prevention strategy among MSM.

Case-Control Studies↗

PubMed2003

Pilot study of COBAS PCR and ligase chain reaction for detection of rectal infections due to Chlamydia trachomatis.

We tested rectal specimens from men who have sex with men for Chlamydia trachomatis by using COBAS PCR (Roche Diagnostics) and ligase chain reaction LCR (Abbott laboratories) and compared three PCR specimen-processing procedures. Chlamydiae were detected by one or more procedures in 22 of 186 specimens. All three PCR tests were positive for 17 specimens, all of which also tested positive by LCR.

Chlamydia Infections↗

PubMed2003

High-risk behaviors among men who have sex with men in 6 US cities: baseline data from the EXPLORE Study.

OBJECTIVES: We describe the prevalence of risk behaviors at baseline among men who have sex with men (MSM) who were enrolled in a randomized behavioral intervention trial conducted in 6 US cities. METHODS: Data analyses involved MSM who were negative for HIV antibodies and who reported having engaged in anal sex with 1 or more partners in the previous year. RESULTS: Among 4295 men, 48.0% and 54.9%, respectively, reported unprotected receptive and insertive anal sex in the previous 6 months. Unprotected sex was significantly more likely with 1 primary partner or multiple partners than with 1 nonprimary partner. Drug and alcohol use were significantly associated with unprotected anal sex. CONCLUSIONS: Our findings support the continued need for effective intervention strategies for MSM that address relationship status, serostatus of partners, and drug and alcohol use.

Adolescent↗

PubMed2003

An individually tailored intervention for HIV prevention: baseline data from the EXPLORE Study.

OBJECTIVES: We describe the intervention tested in EXPLORE, an HIV prevention trial aimed at men who have sex with men (MSM), and test the empirical basis of the individually tailored intervention. METHODS: Data on participants' self-efficacy, communication skills, social norms, and enjoyment of unprotected anal intercourse were examined in relation to sexual risk. Combinations of these factors, together with alcohol use and noninjection drug use, were also examined. RESULTS: The individual factors examined were associated with sexual risk behavior. The cohort was shown to be heterogeneous in regard to the presence of combinations of these risk-related factors. CONCLUSIONS: Baseline data from the EXPLORE study support the efficacy of the individually tailored intervention used.

Adolescent↗

PubMed2002

Sexually transmitted diseases and human immunodeficiency virus-discordant partnerships among men who have sex with men.

Sexually active men who have sex with men (MSM) at 5 Seattle clinics were assessed for bacterial sexually transmitted diseases (STDs), human immunodeficiency virus (HIV)-discordant partnerships, sexual behavior, and drug use. Of the HIV-positive men, 45% reported having HIV-negative sex partners and 42% reported having sex partners with unknown serostatus during the past 2 months, whereas 14% and 57% of HIV-negative men reported having HIV-positive and unknown-serostatus sex partners, respectively. Correlates of sex partners with unknown serostatus were recruiting sex partners at bathhouses or parks. Gonorrhea, chlamydia, or syphilis was diagnosed in 12% of HIV-positive and 13% of HIV-negative MSM, and the rates did not differ between men with HIV-concordant and HIV-discordant partnerships. High prevalences of bacterial STDs and HIV-discordant partnerships emphasize the need for interventions to foster serostatus discussion, condom use, fewer anonymous partners, and STD screening.

Adult↗