PROCAARE: STD control to prevent HIV

[procaare@usa.healthnet.org]

At the 6th Conference on Retroviruses and Opportunistic Infections, Dr.
Marie Laga from the Institute of Tropical Medicine, Antwerp, Belgium,
presented a lecture entitled: "STD control to prevent HIV: Controversies
surrounding the two recent clinical trials: Mwanza vs. Rakai".

This lecture summarized results from two recent trials evaluating distinct
STD interventions for effects on the incidence of HIV infection.  The
first, by Grosskurth et al. (Lancet, 1995) was a community level
intervention trial including 6 matched pairs of rural districts in
Tanzania.  These were divided into control districts and those receiving
the intervention.  This intervention consisted of:

STD reference center in Mwanza town
Training of health care workers in a syndromic approach to STD care,
health education, and condom promotion.
Regular supply of effective STD drugs ensured via a separate distribution
system.
Regular supervisory visits to health centers.
Periodic visits to villages by health educators to promote prompt
attendance to health centers for symptomatic STD.

After two years of follow-up, HIV incidence decreased in all 6
intervention communities relative to their matched control districts.  HIV
infection overall in the intervention districts decreased by 42%.

The second study took place in Rakai, Uganda.  Again, there were paired
intervention and control clusters (5 pairs).  This was a trial of mass
treatment every 9 months to all consenting permanent residents of the
districts between the ages of 15-59.  

The intervention clusters (7871 individuals) received: Azithromycin 1000
mg, Ciprofloxacin 250 mg, Metronidazole 2 gm.

Control clusters (7256 individuals) received: Mebendazole 100 mg,
Iron/Folate, Low-dose multivitamin.

Free care for symptomatic STD was available through a Project Mobile
Clinic, during mass treatments.  Persons symptomatic at other times were
encouraged to employ regular services.

After 3 rounds of mass treatment extending over 20 months, the incidence
of HIV infection was similar in both intervention and control clusters
(about 1.5 per 100 person years).  The proportion of HIV infections
prevented in the Mwanza study was 38% (95% CI 15-55%) vs. 3% in the Rakai
study (-19 to 16%).

Several reasons may exist for the differences in outcome in these two
trials.

STD interventions were of course, very different, with continuous access
to improved STD services in Mwanza, versus intermittent mass treatment of
the general population in Rakai (reinfection depends on coverage,
mobility, migration) with little effective treatment between rounds.  In
the Rakai trial of mass treatment, only Trichomonas and syphilis showed a
significant decrease in incidence in the intervention group (syphilis and
urethritis were significantly decreased in the Mwanza trial).  Improved
case management and health care-seeking behavior were the cornerstones of
the Mwanza trial, and as a result, correct therapy was prescribed and
obtained in 74% in the intervention group vs. 20% control.

Another possible difference between the trials would consider whether
asymptomatic STDs could be relative less important co-factors for HIV
transmission (e.g. inflammation may enhance HIV replication and
transmissibility).  In this context, differences in STD profiles may have
influenced the results; the incidence of Herpes Simplex genital ulcers was
10-20% in the Mwanza trial, vs. 45% in Rakai.

In addition, the two areas were at different stages of the HIV epidemic,
with a baseline prevalence of 16% in Rakai and 4% in Mwanza.  Potentially,
the proportion of new HIV infections attributable to the cofactor effect
of STD may decrease as the epidemic matures and more of the general
population becomes infected.

Certainly, the Rakai trial indicates that mass treatment of STD for the
general population is not effective.  Moreover, mass treatment is
associated with major logistical difficulties and high cost, and may also
promote drug resistance.  It also bypasses health services and takes away
responsibility for health behavior.

The results of the Mwanza trial support the contention that improving the
quality of STD case management at the primary care level should be the
priority.  Certainly, the scope for improvement is enormous in most
countries, and the expertise is available.  

Future questions remain, such as aspects of operational feasibility and
sustainability of interventions.  The role of asymptomatic STDs remains to
be definitively defined.  Measures should be designed for strengthening
STD management at the first encounter, and strategies for targeted
interventions among vulnerable groups (e.g. commercial sex workers) need
to be developed.  However, as stated by Dr. Laga, the question of
improvements in STD case management is "not whether it should be done, but
how it should be done."

Keywords: clinical science, epidemiology, sexually transmitted disease,
STD, HIV, prevention, intervention, mass treatment, Mwanza, Rakai,
Tanzania, Uganda

Summarized by: Albert Shaw <ashaw@usa.healthnet.org>

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