Impact of acyclovir on genital and plasma HIV-1 RNA, genital herpes simplex virus type 2 DNA, and ulcer healing among HIV-1-infected African women with herpes ulcers: a randomized placebo-controlled trial.

BACKGROUND: Little is known about the impact of episodic treatment of herpes on human immunodeficiency virus type 1 (HIV-1). METHODS: Women from Ghana and the Central African Republic who had genital ulcers were enrolled in a randomized, double-blind, placebo-controlled trial of acyclovir plus antibacterials and were monitored for 28 days. Ulcer etiologies and detection of lesional HIV-1 RNA were determined by polymerase chain reaction (PCR). Cervicovaginal HIV-1 RNA and herpes simplex virus type 2 (HSV-2) DNA and plasma HIV-1 RNA were quantitated by real-time PCR. Primary analyses included 118 HIV-1-infected women with HSV-2 ulcers (54 of whom were given acyclovir and 64 of whom were given placebo). RESULTS: Acyclovir had little impact on (1) detection of cervicovaginal HIV-1 RNA (risk ratio [RR], 0.96; 95% confidence interval [CI], 0.8-1.2) at day 7 of treatment, (2) the mean cervicovaginal HIV-1 RNA load (-0.06 log(10) copies/mL; 95% CI, -0.4 to 0.3 log(10) copies/mL) at day 7 of treatment, or (3) the plasma HIV-1 RNA load (+0.09 log(10) copies/mL; 95% CI, -0.1 to 0.3 log(10) copies/mL) at day 14 of treatment. At day 7, women receiving acyclovir were less likely to have detectable lesional HIV-1 RNA (RR, 0.70; 95% CI, 0.4-1.2) or cervicovaginal HSV-2 DNA (RR, 0.69; 95% CI, 0.4-1.3), had a lower quantity of HSV-2 DNA (-0.99 log(10) copies/mL; 95% CI, -1.8 to -0.2 log(10) copies/mL), and were more likely to have a healed ulcer (RR, 1.26; 95% CI, 0.9-1.9). CONCLUSION: Episodic therapy for herpes reduced the quantity of cervicovaginal HSV-2 DNA and slightly improved ulcer healing, but it did not decrease genital and plasma HIV-1 RNA loads. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00158483 .

Performance of HerpeSelect and Kalon assays in detection of antibodies to herpes simplex virus type 2.

The performances of commercial enzyme-linked immunosorbent assays (ELISAs) in detecting herpes simplex virus type 2 (HSV-2) antibodies have been inconsistent for African and human immunodeficiency virus (HIV)-positive populations. We compared the performances of the HerpeSelect and Kalon glycoprotein G2 ELISAs for patients with genital ulcer disease in Ghana and the Central African Republic. Sera from 434 women were tested with the HerpeSelect assay, and a subsample (n = 199) was tested by the Kalon assay. Ulcer swabs and cervicovaginal lavage samples were tested for HSV-2 DNA by PCR. HSV-2-seronegative women with detectable genital HSV-2 DNA were retested for HSV-2 antibodies 14 and 28 days later by the two ELISAs. A total of 346 (80%) women were positive by HerpeSelect at baseline, and 225 (54%) had detectable genital (lesional or cervicovaginal) HSV-2 DNA. Sixty-six (19%) HerpeSelect-positive samples had low-positive index values (1.1 to 3.5), and 58% of these samples had detectable genital HSV-2 DNA. Global agreement between the two serological assays was 86%. Concordance was high (99%) for sera that were negative by HerpeSelect or had high index values (>3.5). Defining infection detected by HSV-2 DNA PCR and/or Kalon assay as true infection, 71% of sera with low-positive index values were associated with true HSV-2 infection. Twenty-five women were identified as having nonprimary first-episode genital HSV-2 infection. Rates of HSV-2 seroconversion at day 14 were 77% (10/13 patients) by HerpeSelect assay and 23% (3/13 patients) by Kalon assay, with four additional seroconversions detected by Kalon assay at day 28. HIV serostatus did not influence assay performance. Low index values obtained with the HerpeSelect assay may correspond to true HSV-2 infection, in particular to nonprimary first episodes of genital HSV-2 infection, and need to be interpreted in the context of clinical history.

Cervicovaginal HIV-1 and herpes simplex virus type 2 shedding during genital ulcer disease episodes.

OBJECTIVE: To investigate correlates of herpes simplex virus type 2 (HSV-2) DNA and HIV-1 RNA among women with genital ulcer disease (GUD). DESIGN: Baseline data from a randomized placebo-controlled trial of episodic herpes treatment in Ghana and the Central African Republic. METHODS: GUD aetiology was determined by polymerase chain reaction (PCR) from a lesional swab. Real-time PCR was used to quantify HIV-1 RNA, and HSV-2 DNA in cervicovaginal lavages (CVL) and HIV-1 RNA in plasma. Genital infection was defined as the presence of virus in the lesion or CVL. RESULTS: Of 441 women enrolled, 79.0% were HSV-2 seropositive, 46.6% were HIV-1 seropositive, and 50.0% had an HSV-2 ulcer. Among 180 HSV-2/HIV-1 co-infected women, cervicovaginal HIV-1 RNA was detected more frequently in women with HSV-2 ulcers (67.9%) or cervicovaginal HSV-2 DNA only (72.3%) compared with women without genital HSV-2 infection (42.4%) (P = 0.004). Women with genital HSV-2 infection had higher median cervicovaginal HIV-1-RNA loads (3.14 log10 copies/mL versus 2.10 log10 copies/mL; P = 0.003), higher plasma HIV-1-RNA loads (median 5.10 versus 4.65 log10 copies/mL; P = 0.07), and lower median CD4 cell counts) (198 versus 409 cells/mm, P = 0.03). Cervicovaginal HIV-1 RNA and HSV-2 DNA were significantly correlated after adjusting for plasma HIV-1 RNA and CD4 cell counts (P < 0.001) and a 10-fold increase in cervicovaginal HSV-2 DNA was associated with a 1.7-fold increase in plasma HIV-1 RNA (P = 0.003). CONCLUSION: Genital HSV-2 infection is associated with increased cervicovaginal and plasma HIV-1 RNA among co-infected women with genital ulcers, independently of the level of immunodeficiency, highlighting the close interaction between these two viruses and the role of HSV-2 as a co-factor for the sexual transmission of HIV-1.

Influence of storage temperature on the stability of HIV-1 RNA and HSV-2 DNA in cervicovaginal secretions collected by vaginal washing.

Variability in the handling of samples of genital secretions prior to quantitation of HIV-1 RNA and HSV DNA may profoundly affect both the detection and quantitation of these nucleic acids. Over 144 h, we evaluated, the influence of storage temperature (4 degrees C, 20 degrees C, 30 degrees C) on the quantity of HIV-1 RNA and HSV-2 DNA in HIV and HSV negative cervicovaginal lavage pools spiked with known amounts of HIV-1 and HSV-2 and in HIV-1 and HSV-2 co-infected cervicovaginal lavage pools. The level of viral nucleic acids remained stable at 4 degrees C for 24h but decreased significantly when cervicovaginal lavages were stored at 20 degrees C and 30 degrees C, demonstrating that, cervicovaginal lavages to be quantified for viral RNA or DNA require, at minimum, immediate storage at 4 degrees C.

Transactional sex is the driving force in the dynamics of HIV in Accra, Ghana.

OBJECTIVE: To delineate the population attributable fraction (PAF) of transactional sex in prevalent cases of HIV infection in the male adult population of Accra, Ghana. DESIGN AND METHODS: Cross-sectional study of clients who visited a sex worker (SW), of boyfriends of SW and of male personnel in prostitution venues. A questionnaire was administered and urine obtained for detection of anti-HIV antibodies. The PAF of prevalent HIV acquired from SW was calculated using a combination of data from this survey of clients, from on-going SW surveys, the national HIV surveillance system and the national census. RESULTS: HIV prevalence was 4.9% (8/162) among clients of mobile SW, 15.8% (53/335) among clients of home-based SW, 17.5% (10/57) among personnel and 32.1% (9/28) among boyfriends. A condom was used in 90% of intercourses, according to clients. Non-use of a condom was clustered in selected locations and independently associated with older age of client, frequency of intercourse with SW in the last year and current urethritis. Among the male population of Accra aged 15-59 years, 84% of prevalent cases of HIV were attributable to transactional sex. A sensitivity analysis showed that under various assumptions PAF varied between 47% and 100%. CONCLUSIONS: In Accra, approximately four-fifths of prevalent cases of HIV in adult males were acquired from SW. Comprehensive interventions providing education, condoms and treatment for sexually transmitted diseases for SW and their clients should be approached as other public health priorities and provided in all cities, large and small, of West Africa.