Elsevier

The Lancet

Volume 349, Issue 9069, 28 June 1997, Pages 1868-1873
The Lancet

Articles
Reduction of concentration of HIV-1 in semen after treatment of urethritis: implications for prevention of sexual transmission of HIV-1

https://doi.org/10.1016/S0140-6736(97)02190-9Get rights and content

Summary

Background

Transmission of HIV-1 is predominantly by heterosexual contact in sub-Saharan Africa, where sexually transmitted diseases (STDs) are also common. Epidemiological studies suggest that STDs facilitate transmission of HIV-1, but the biological mechanism remains unclear. We investigated the hypothesis that STDs increase the likelihood of transmission of HIV-1 through increased concentration of the virus in semen.

Methods

HIV-1 RNA concentrations were measured in seminal and blood plasma from 135 HIV-1-seropositive men in Malawi; 86 had urethritis and 49 controls did not have urethritis. Men with urethritis received antibiotic treatment according to the guidelines of the Malawian STD Advisory Committee. Samples were analysed at baseline and at week 1 and week 2 after antibiotic therapy in urethritis patients, and at baseline and week 2 in the control group.

Findings

HIV-1-seropositive men with urethritis had HIV-1 RNA concentrations in seminal plasma eight times higher than those in seropositive men without urethritis (12·4 vs 1·51×104 copies/mL, p=0·035), despite similar CD4 counts and concentrations of blood plasma viral RNA. Gonorrhoea was associated with the greatest concentration of HIV-1 in semen (15·8×104 copies/mL). After the urethritis patients received antimicrobial therapy directed against STDs, the concentration of HIV-1 RNA in semen decreased significantly (from 12·4×104 copies/mL to 8·91×104 copies/mL at 1 week [p=0·03] and 4·12×104 copies/mL at 2 weeks [p=0·0001]). Blood plasma viral RNA concentrations did not change. There was no significant change in seminal plasma HIV-1 RNA concentrations during the 2-week period in the control group (p=0·421).

Interpretation

These results suggest that urethritis increases the infectiousness of men with HIV-1 infection. HIV-1-control programmes, which include detection and treatment of STDs in patients already infected with HIV-1, may help to curb the epidemic. Targeting of gonococcal urethritis may be a particularly effective strategy.

Introduction

In areas most severely affected by the HIV-1 pandemic, viral transmission occurs almost exclusively through heterosexual contact.1 Regional heterogeneity in HIV-1 transmission rates is associated with rapid expansion of epidemics in parts of the developing world and may be explained by behavioural and host-related or virus-related biological factors.1, 2 The development of practical and affordable strategies to prevent heterosexual HIV-1 transmission requires a more detailed understanding of reversible biological factors that influence viral transmission.3

Epidemiological studies provide strong evidence that ulcerative and non-ulcerative sexually transmitted diseases (STDs) significantly increase the risk of acquiring HIV-1.4, 5 Consistent with this evidence, improved treatment of STDs in Tanzania was associated with a 42% reduction in the incidence of HIV-1 infections.6 Although the biological mechanism remains unclear, inflammation associated with STDs enriches mucosal tissues with activated cells that are receptive to HIV-1 infection, and could increase physical access to such cells.7 Equally important, STDs and reproductive-tract inflammation may increase levels of HIV-1 shedding in genital secretions and lead to increased infectiousness and a greater possibility of HIV-1 transmission.8, 9, 10, 11

We measured concentrations of HIV-1 RNA in cell-free seminal plasma from HIV-1-seropositive men with urethritis before and after antibiotic therapy. The results were compared with those seen in HIV-1-seropositive men who had no clinical evidence of urethritis.

Section snippets

Methods

We did this study at the Kamuzu Central Hospital in Lilongwe, Malawi, between January and March, 1996. The protocol was approved by the University of North Carolina Committee on the Protection of Human Rights and the Malawi Health Sciences Research Committee. All study participants gave informed consent and were offered a small payment for their participation. The study design was a prospective, sequential comparison of two cohorts: HIV-1-infected men with urethritis, selected from the STD

Results

206 men with urethritis (the STD group) and 127 controls were enrolled (table). 113 (55%) men from the STD-clinic group and 60 (48%) controls from the dermatology clinics were HIV-1 seropositive, which is consistent with our previous findings in Malawi.12, 13 86 HIV-1-seropositive men in the STD group and 49 seropositive controls with no urethritis provided baseline semen samples. Of these, 81 and 74 STD-group patients, respectively, provided semen 1 week (median 7 days [range 5–8]) and 2 weeks

Discussion

The efficiency of transmission of HIV-1 most likely reflects the phenotype of the virus,16 the size of the inoculum,17, 18, 19 and host genetic and immune factors.20, 21, 22 The concentration of HIV-1 RNA in blood plasma correlates with the likelihood of transmission by blood transfusion, as well as by vertical and heterosexual routes.17, 18, 19 Sexual transmission of HIV has even greater variability in efficiency than other routes,23 and this variability has been ascribed to cofactors that

References (34)

  • MC Dickerson et al.

    The causal role for genital ulcer disease as a risk factor for transmission of human immunodeficiency virus: an application of the Bradford Hill Criteria

    Sex Transm Dis

    (1996)
  • GB Moss et al.

    Human immunodeficiency virus DNA in urethral secretions in men: association with gonococcal urethritis and CD4 cell depletion

    J Infect Dis

    (1995)
  • MC Atkins et al.

    Fluctuations of HIV load in semen of HIV positive patients with newly acquired sexually transmitted diseases

    BMJ

    (1996)
  • JJ Eron et al.

    HIV-1 shedding and chlamydial urethritis

    JAMA

    (1996)
  • J Kreiss et al.

    Association between cervical inflammation and cervical shedding of HIV DNA

    J Infect Dis

    (1994)
  • G Lule et al.

    STD/HIV control in Malawi and the search for affordable and effective urethritis therapy: a first field evaluation

    Genitourin Med

    (1994)
  • FM-T Behets et al.

    Sexually transmitted diseases and human immunodeficiency virus control in Malawi: a field study of genital ulcer disease

    J Infect Dis

    (1995)
  • Cited by (741)

    View all citing articles on Scopus

    Members listed at end of paper

    View full text