Association between Human Immunodeficiency Virus and Herpes Simplex Virus
Type 2 Seropositivity among Male Factory Workers in Zimbabwe
Lovemore Gwanzura, William McFarland,
D’Anna Alexander, Rae Lyn Burke,
and David Katzenstein
Department of Medical Laboratory Technology, University of
Zimbabwe, Harare; Center for AIDS Prevention Studies, University of
California, San Francisco, Chiron Corporation, Emeryville, and
Department of Infectious Diseases and Geographic Medicine, Stanford
University, Stanford, California
To determine the seroprevalence of herpes simplex virus type 2 (HSV-2), to identify correlates of
infection, and to describe the correlation with human immunodeficiency virus (HIV) seropositivity,
224 HIV-negative and 191 HIV-positive male factory workers in Zimbabwe were screened for HSV-
2–specific antibodies. HSV-2 seroprevalence was 35.7% among HIV-negative subjects and 82.7%
among HIV-positive subjects. The weighted estimate of HSV-2 seroprevalence in this population is
44.6%. The correlation between HIV and HSV-2 remained significant after controlling for multiple
sex partners, paying for sex, and history of sexually transmitted disease (adjusted odds ratio, 8.0;
95% confidence interval, 4.8–13.1). If the association between HSV-2 and HIV is causal, then the
high seroprevalence of HIV and HSV-2 suggests that suppressive HSV-2 treatment should be
considered as a strategy to reduce HIV transmission in this population. HSV-2 seroconversion may
be a suitable surrogate end point to evaluate HIV prevention interventions.
Epidemiologic and biologic evidence increasingly impli-
cate sexually transmitted diseases (STDs) as causal factors
in human immunodeficiency virus (HIV) transmission .
The relatively high prevalence of untreated STDs in sub-
Saharan Africa has been proposed as a contributing factor in
the higher prevalence of heterosexually transmitted HIV in
that region compared with the industrialized world . The
hypothesis is supported by the success of an HIV prevention
intervention based on community-wide enhanced STD treat-
ment in Mwanza, Tanzania .
STDs that cause genital ulceration, such as syphilis, chan-
croid, and herpes simplex virus type 2 (HSV-2) infection, are
particularly implicated in facilitating HIV transmission [1, 4].
Genital ulcer disease (GUD) is believed to increase the risk of
HIV acquisition per sexual exposure by increasing the amount
of HIV shedding through genital lesions and by providing an
easy portal of entry of the virus into the host .
Although GUD is a common complaint at STD clinics in
Africa, screening for HSV-2 is rarely done. Nonetheless, recent
studies confirm that HSV-2 is common in adult populations on
the continent. Laboratory evidence of HSV-2 was present
among 36% of GUD patients in Kampala . In one study that
screened stored sera from Dakar, HSV-2 seroprevalence ranged
from 20% of surgical patients to as high as 96% among prosti-
tutes . Considering the high prevalence of HSV-2, the in-
creased shedding of HIV through genital herpes lesions, and
the fact that persons with HSV-2 remain potentially infectious
for life, HSV-2 may account for a large proportion of HIV
infection in Africa.
To determine the prevalence of HSV in a population of
male factory workers in Harare, Zimbabwe, we screened stored
serum specimens from subjects participating in an HIV preven-
tion intervention for HSV-1– and HSV-2–specific antibodies.
The availability of HIV serostatus at enrollment in the interven-
tion as well as demographic and sexual risk–related data per-
mitted examination of the correlation between HIV and HSV-
2 seropositivity in case-control analysis.
Received 15 May 1997; revised 2 September 1997.
Presented in part: International Union of Immunologic Sciences Meeting,
Capetown, South Africa, 9–14 March 1997.
The study was carried out as part of HIVNET 011, for which written in-
formed consent was obtained from all participants. Human experimentation
guidelines of the US Department of Health and Human Services, the National
Commission for the Protection of Human Subjects of Biomedical and Behav-
ioral Research,Stanford University MedicalCenter InstitutionalReview Board,
and the Medical Research Council of Zimbabwe were followed.
D.A.A. and R.L.B. are employees of Chiron Corporation.
Financial support: NIH (AI-33868); Preparation for AIDS Vaccine Evalua-
tion (PAVE); and HIVNET 011. HSV1/2 assays were provided by Chiron.
Reprints or correspondence: Dr. William McFarland, Seroepidemiology
Unit, AIDS Office, San Francisco Dept. of Public Health, 25 Van Ness Ave.,
Suite 500, San Francisco, CA 94102-6033 (Willi_McFarland@dph.sf.ca.us).
HSV-1–specific antibodies originated from subjects enrolled in the
Zimbabwe AIDS Prevention Project, a longitudinal cohort study
established to determine the prevalence, incidence, and correlates
of HIV infection and to evaluate a peer education intervention.
Recruitment and follow-up methods and observational findings of
the cohort have been described in detail elsewhere [8, 9]. Briefly,
subjects are male factory workers recruited and followed at 40
work sites in greater Harare, Zimbabwe. At enrollment and at
6-month intervals, subjects are interviewed on HIV risk–related
behaviors, and blood is drawn for serologic testing for HIV, syphi-
Serum specimens screened for HSV-2– and
The Journal of Infectious Diseases
? 1998 by The University of Chicago. All rights reserved.
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