Article

Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand.

National Center for HIV, Viral Hepatitis and STD Prevention, Centers for Disease Control and Prevention, Atlanta, GA, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 10/2008; 49(1):77-83. DOI: 10.1097/QAI.0b013e3181831832
Source: PubMed

ABSTRACT Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. We evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding.
HIV-1- and herpes simplex virus type 2-coinfected women aged 18-49 years with CD4 counts >200 cells/microL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared.
Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/microL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001).
Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effect of suppressive therapy on HIV transmission.

0 Followers
 · 
175 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The HIV RNA viral load (VL) in vaginal secretions and semen is an independent predictor of HIV transmission. Blood VL is associated with semen VL, and local mucosal factors such as semen CMV reactivation may play an important role. Twenty-one HIV-CMV co-infected, antiretroviral-naïve men received 900mg of oral valganciclovir once daily for two weeks in an open-label study. Blood and semen were collected at baseline, after two weeks of valganciclovir, and two months after therapy completion. The primary endpoint was change in semen HIV levels at 2 weeks; secondary endpoints were change in semen HIV VL at 2 months and change in semen CMV levels. The HIV VL fell significantly at 2 weeks in semen (median 3.44 to 3.02 log10 copies/ml; p=0.02) and blood (median 3.61 to 3.10 log10 copies/ml; p<0.01), and returned to baseline after therapy completion (median 3.24 and 3.71 log10 copies/ml in semen and blood, respectively). Semen CMV levels also fell on treatment (median log10, 2.13 to 1.62; p<0.01), and continued to fall after therapy completion (median 0.91 log10 copies/ml at week 8; p<0.001 vs. baseline). The reduced semen CMV VL was associated with decreased semen T cell activation and enhanced CMV-specific T cell responses in blood; changes in the semen HIV VL were not associated with immune parameters. While valganciclovir therapy was associated with reduced HIV and semen CMV levels, these results suggest that the reduced HIV VL was a direct drug effect, rather than via a CMV antiviral effect or CMV-associated immune alterations.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 10/2013; 65(3). DOI:10.1097/01.qai.0000435256.34306.c1 · 4.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: : Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother-to-child transmission. In recent years, antiretroviral drugs to reduce the risk of transmission (when the infected person takes the medicines; treatment as prevention) or reduce the risk of acquisition (when the seronegative person takes them; preexposure prophylaxis) have proven to be efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (ie, screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV-prevention strategies such as family planning for HIV-infected women who do not want more children and prevention of mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 06/2013; 63 Suppl 1:S12-25. DOI:10.1097/QAI.0b013e31829202a2 · 4.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the long-term effects of population-level HSV-2 infection on HIV incidence. Data from a population-based cohort in south-western Uganda were used to estimate HIV incidence from 1990 to 2007. Stored blood samples were tested for HSV-2, and the impact of HSV-2 prevalence and incidence on HIV incidence was estimated by calculating population attributable fractions (PAFs). The association between population-level annual HIV incidence and annual HSV-2 incidence/prevalence was analysed using linear regression. HIV incidence declined over time among men, from 8.72/1000 person-years (pyr) in 1990 to 4.85/1000 pyr in 2007 (P-trend <0.001). In contrast, there was no decline in HIV incidence among women (4.86/1000 pyr in 1990 to 6.74/1000 pyr in 2007, P-trend = 0.18). PAFs of incident HIV attributable to HSV-2 were high (60% in males; 70% in females). There was no evidence of an association between long-term trends in HIV incidence and HSV-2 prevalence or incidence. Assuming a causal relationship, a substantial proportion of new HIV infections in this population are attributable to HSV-2. The study did not find an effect of HSV-2 prevalence/incidence on trends in HIV incidence. HIV incidence did not vary much during the study period. This may partly explain the lack of association.
    Tropical Medicine & International Health 10/2013; 18(10):1257-66. DOI:10.1111/tmi.12176 · 2.30 Impact Factor