RESUMO
BACKGROUND: Antiretroviral therapy (ART) may decrease HIV-1 infectivity in women by reducing genital HIV-1 shedding. OBJECTIVES: To evaluate the time course and magnitude of decay in cervical and vaginal HIV-1 shedding as women initiate ART. METHODS: This prospective, observational study of 20 antiretroviral-naive women initiating ART with stavudine, lamivudine, and nevirapine measured HIV-1 RNA in plasma, cervical secretions, and vaginal secretions. Qualitative polymerase chain reaction estimated HIV-1 DNA in cervical and vaginal samples. Perelson's two-phase viral decay model and non-linear random effects were used to compare RNA decay rates. Decreases in proviral DNA were evaluated using logistic regression and generalized estimating equations. RESULTS: Significant decreases in the quantity of HIV-1 RNA were observed by day 2 in plasma (P < 0.001), day 2 in cervical secretions (P = 0.001), and day 4 in vaginal secretions (P < 0.001). Modeled initial and subsequent RNA decay rates in plasma, cervical secretions, and vaginal secretions were 0.6, 0.8, and 1.2 log10 virions/day, and 0.04, 0.05, and 0.06 log10 virions/day, respectively. The initial decay rate for vaginal HIV-1 RNA was more rapid than for plasma RNA (P = 0.02). Detection of HIV-1 DNA decreased significantly in vaginal secretions during the first week (P < 0.001). At day 28, 10 women had detectable HIV-1 RNA or proviral DNA in genital secretions. CONCLUSIONS: Genital HIV-1 shedding decreased rapidly after ART initiation, consistent with a rapid decrease in infectivity. However, incomplete viral suppression in half of these women may indicate an ongoing risk of transmission.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Colo do Útero/virologia , Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Vagina/virologia , Adulto , Terapia Antirretroviral de Alta Atividade , DNA Viral/análise , Feminino , Seguimentos , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Estudos Prospectivos , Provírus/isolamento & purificação , RNA Viral/análise , RNA Viral/sangue , Trabalho Sexual , Resultado do TratamentoRESUMO
Few data are available on genital tract viral replication early after HIV-1 acquisition, when infectivity is high. We compared cervical HIV-1 RNA from 60 women with paired samples from within 90 days after HIV-1 acquisition and at viral setpoint (4-24 months). Cervical HIV-1 was higher in early compared with setpoint samples (mean 3.43 versus 2.85 log10 copies/swab, P < 0.001). After adjusting for HIV-1-plasma RNA, cervical HIV-1 RNA from 30 days or less after infection was increased by 0.45 log10 copies/swab (P = 0.006).
Assuntos
Colo do Útero/virologia , Infecções por HIV/virologia , HIV-1/fisiologia , RNA Viral/análise , Feminino , Humanos , Estudos Prospectivos , RNA Viral/sangue , Carga Viral , Replicação Viral/fisiologiaRESUMO
The prevalence of human immunodeficiency virus (HIV)-1-infected cells and HIV-1 RNA levels in genital secretions and breast milk and the risk of mother-to-child transmission of HIV-1 were compared among subtypes A, C, and D in a Kenyan cohort. Pregnant women infected with subtype C were significantly more likely to shed HIV-1-infected vaginal cells than were those infected with subtype A or D (odds ratio [OR], 3.6 [95% confidence interval {CI}, 1.4-8.8]; P = .006). This relationship held after adjusting for age, CD4 cell count, and plasma HIV-1 RNA load (OR, 3.1 [95% CI, 1.1-8.6]; P = .03). These observations suggest that HIV-1 subtype influences mucosal shedding of HIV-1.
Assuntos
Colostro/virologia , Soropositividade para HIV/transmissão , HIV-1/isolamento & purificação , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez/virologia , Vagina/virologia , Eliminação de Partículas Virais , Feminino , HIV-1/classificação , Humanos , Recém-Nascido , Filogenia , Gravidez , RNA Viral/sangue , Carga ViralRESUMO
We examined the association between host factors present near the time of human immunodeficiency virus type 1 (HIV-1) acquisition and subsequent virus loads, in a prospective cohort study of women in Mombasa, Kenya. Women were prospectively followed monthly before HIV-1 infection. One hundred sixty-one commercial sex workers who became infected with HIV-1 were followed for a median of 34 months, and 991 plasma samples collected > or =4 months after infection were tested for HIV-1 RNA. The median virus set point at 4 months after infection was 4.46 log10 copies/mL, and the average virus load increase during subsequent follow-up was 0.0094 log10 copies/mL/month. In a multivariate analysis that controlled for sexual behavior, the use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) at the time of HIV-1 infection was associated with a higher virus set point, and the presence of genital ulcer disease (GUD) during the early phase of HIV-1 infection was associated with greater change in virus load during follow-up. These findings suggest that, in women, the use of DMPA and the presence of GUD during the early phase of HIV-1 infection may influence the natural course of infection.
Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Anticoncepcionais Femininos/administração & dosagem , Doenças dos Genitais Femininos/virologia , HIV-1/isolamento & purificação , Acetato de Medroxiprogesterona/administração & dosagem , Úlcera/virologia , Adulto , Estudos de Coortes , Feminino , Humanos , Injeções , Análise Multivariada , Estudos Prospectivos , RNA Viral/sangue , Comportamento Sexual , Carga ViralRESUMO
Steady-state levels of human immunodeficiency virus type 1 (HIV-1) RNA in plasma reached at approximately 4 months postinfection are highly predictive of disease progression. Several studies have investigated viral levels in adults or infants during primary and early infection. However, no studies have directly compared these groups. We compared differences in peak and set point plasma HIV-1 RNA viral loads among antiretrovirus-naive Kenyan infants and adults for whom the timing of infection was well defined. Peak and set point viral loads were significantly higher in infants than in adults. We did not observe any gender-specific differences in viral set point in either adults or infants. However, infants who acquired HIV-1 in the first 2 months of life, either in utero, intrapartum, or through early breast milk transmission, had significantly higher set point HIV-1 RNA levels than infants who were infected after 2 months of age through late breast milk transmission or adults who were infected through heterosexual transmission.
Assuntos
Infecções por HIV/virologia , HIV-1/fisiologia , Carga Viral , Doença Aguda , Adulto , Aleitamento Materno , Estudos de Coortes , Progressão da Doença , Transmissão de Doença Infecciosa , Feminino , Infecções por HIV/fisiopatologia , Infecções por HIV/transmissão , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Quênia , Masculino , RNA Viral/sangue , Fatores de Tempo , Replicação ViralRESUMO
We evaluated the association between the severity of primary human immunodeficiency virus type 1 (HIV-1) illness and HIV-1 plasma virus load before seroconversion using stored plasma samples obtained from 74 prostitutes in Mombasa, Kenya. Fever, vomiting, headache, fatigue, arthralgia, myalgia, sore throat, skin rash, or being too sick to work were each associated with significantly higher virus loads before HIV-1 seroconversion, and each additional symptom or sign was associated with an increase in virus load of 0.4 log(10) copies/mL.