Scientific Evaluation of Peer Education and STD Treatment to Reduce the Spread of HIV in Zimbabwe
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether community-based peer education and condom
      distribution combined with improved treatment of sexually transmitted infections are
      effective in reducing the spread of HIV infection in a sub-Saharan African population
    

Detailed description: 
      Background and Literature Review

      The Spread and Early Demographic Impact of HIV in Zimbabwe

      High levels of HIV prevalence and incidence have been recorded in Zimbabwe since sentinel
      surveillance was introduced in 1990. Prevalence levels in excess of 40% have been recorded
      among women attending antenatal clinics in a number of urban centres [1,2]. In a cohort study
      of male factory workers conducted in Harare between 1993 and 1995, 19% of participants were
      found to have the infection at enrolment and an incidence rate of 2.93% per annum was
      recorded [3]. However, rural areas - where 70% of the country's population are based - are
      experiencing some of the highest rates of incidence at the current time. In Mberengwa,
      Midland Province, HIV prevalence among pregnant women increased from under 8% in 1992 to 25%
      in 1994 [4].

      In a study in two rural areas of Manicaland Province, we also found high levels of HIV
      infection at antenatal clinics in 1993-94 - 24% and 14%, at the growth points in the Honde
      Valley and the Rusitu Valley, respectively. Further data from the Honde Valley in 1996
      indicate that incidence remains high (2-4%). Significant increases in adult and infant
      mortality and in orphanhood were recorded. The cause-specific and age-patterns of increase
      indicate that these are due primarily to HIV infections. Sexual intercourse with casual
      partners is common and condom use is low. In qualitative studies, high proportions of men,
      but relatively few women, reported recent casual partnerships. Mathematical model simulations
      indicate that this pattern of behaviour could explain the greater excess mortality that was
      recorded among males, given a recent - last 4-5 years - escalation of the HIV epidemic in
      rural areas. Other ulcerative and non-ulcerative sexually transmitted diseases (STDs) are
      common, but only 2% of respondents were aware that STDs can facilitate HIV transmission [5
      8].

      Mathematical model projections, based on our understanding of the predominant behaviour
      pattern and fitted to observed trends in HIV prevalence, also indicate that further increases
      in adult and early childhood mortality are to be expected. Results from these simulations and
      empirical findings from Uganda suggest that these increases will result in adverse indirect
      effects, including high proportions of children experiencing orphanhood and distortions in
      the age- and sex-distribution of the population [9,10]. These effects may be compounded by
      fertility change. Birth rates are declining in rural areas of Zimbabwe at present and the HIV
      epidemic may re-enforce this decline through changes in behaviour or underlying fecundity
      [11]. Women with HIV infection are reported as having lower fertility than other women in
      Ugandan studies [12] and results from our research in Manicaland indicate that behaviour
      changes which would tend to re-enforce the existing decline in birth rates may be beginning
      to occur [7].

      HIV Prevention Strategies

      Mathematical model simulations have demonstrated the potential for reducing the incidence of
      new HIV infections through biomedical and behavioural interventions. The benefits of early
      interventions and of targeting interventions at core groups have been emphasized [13,14].
      Targeted interventions are liable to be less effective if introduced after high levels of HIV
      prevalence have been reached. Their success will also depend on the level of heterogeneity in
      sexual activity which exists within a population and the predominant pattern of mixing
      between different risk groups [15]. Combinations of intervention approaches can act
      additively and even synergistically [16].

      In one set of simulations, based on epidemiological data from rural Uganda, it was
      demonstrated that a combined biomedical and behavioural intervention which (a) increased
      condom use in contacts between men and casual sex partners to 50%, (b) reduced the frequency
      of these contacts by 50%, and (c) reduced the average duration of STD episodes by 50%, could
      reduce HIV incidence by 50% in the first year and 80% over ten years. Empirical studies have
      shown that changes of this nature are possible and can lead to large reductions in HIV
      incidence. In Nairobi, health education and condom promotion led to an increase in condom use
      among commercial sex workers from 8% to 66%. Condom use was associated with a 3-fold
      reduction in risk of sero-conversion [17]. In Zimbabwe, large-scale condom promotion
      programmes were associated with 48% and 53% reductions in STD cases over three years, in
      Bulawayo and Mutare, respectively. Most of these reductions were achieved within the first
      year of the intervention [18]. In a study of 752 male factory workers in Mwanza, Tanzania,
      counselling at an STD clinic contributed to significant reductions in reported high-risk
      behaviour - eg: the proportion with more than one sexual partner in the preceding month fell
      from 22% to 12% - and a large (63%) - but non-significant - reduction in HIV incidence
      [19,20]. In a randomized control trial in rural areas around Mwanza, improved diagnosis and
      treatment of STDs was associated with a 42% reduction in the incidence of new HIV infections
      over a two-year period [21,22].

      While these examples demonstrate the effectiveness of individual interventions, there remain
      shortages of scientific evaluations of combined approaches and of programmes which are
      sustainable within rural communities, where the majority of sub-Saharan African populations
      are based and where HIV is now spreading rapidly [23]. Studies of this kind are essential to
      establish the effectiveness of different intervention strategies and to provide demonstration
      models which can be used to promote the implementation of interventions which are appropriate
      and cost-effective.

      Care and Support Interventions

      As HIV epidemics begin to cause higher morbidity, mortality, orphanhood and socio-economic
      hardship, affected communities require interventions which provide support in coping with
      these problems, particularly so, as institution-based solutions become less viable. This need
      is often upper-most in people's minds, so that prevention programmes which are linked to care
      initiatives - especially where infected community members are supported and involved in
      prevention - are considered likely to be most effective [24]. Few systematic evaluations have
      been conducted to assess the effectiveness of existing care and support models. However, it
      is clear that programmes which include a high level of external biomedical input are unlikely
      to be financially sustainable [25]. On the other hand, early evaluations indicate that
      initiatives which encourage local community ownership and participation, whilst more limited
      in scope, can be extremely cost-effective [26].

      Community-Based, HIV Prevention, Care and Support Intervention Strategy for Rural Zimbabwe

      In the light of the above, it is proposed to initiate a community-based, combined HIV
      prevention, care and support intervention in the Honde Valley and neighbouring areas of the
      Mutasa District of rural Manicaland. The proposed intervention will ultimately cover an area
      of approximately 2,750 square kilometres, comprising a population of around 170,000 people.
      The project will be a collaborative programme promoted by Family AIDS Caring Trust (FACT) and
      the Biomedical Research and Training Institute (BRTI) and involving local community and
      church groups and local Ministry of Health personnel. FACT is a Zimbabwean NGO based in
      Mutare, the provincial capital of Manicaland, and has a well-deserved reputation as an
      organization which has pioneered innovative community-based HIV control activities in
      Zimbabwe. Its' established projects include prevention and support programmes in both urban
      and rural areas of the province. FACT will be responsible for behavioural (including condom
      promotion and distribution activities and community-based promotion of STD services), support
      and care aspects of the programme. BRTI is a relatively recently-formed organization based in
      Harare with strong links with the University of Zimbabwe Medical School, the Blair Research
      Institute and other parts of the Ministry of Health and Child Welfare. BRTI has considerable
      expertise in STD diagnostic methods and treatment regimes and would be responsible for this
      aspect of the intervention and evaluation, in close co-operation with the Ministry of Health
      in Manicaland. It serves a similar function in established HIV control programmes elsewhere
      in Zimbabwe. BRTI would also act as employer for staff engaged to carry out the fieldwork for
      the intervention evaluation.

      PLAN International have recently extended their area of operation in Zimbabwe to include the
      Honde Valley and have agreed to provide funding for the HIV intervention programme for a
      minimum period of four years. PLAN maintain routine records on a number of key impact
      indicators so that the projects they sponsor can be assessed. It may be possible to develop
      these systems so that they provide information on indicators of the impact of the HIV
      epidemic and the effectiveness of AIDS control activities - eg: programme coverage and
      success in targeting - which could be used in this study and for long-term monitoring
      purposes.

      The proposed intervention strategy appears to have good potential for sustainability and
      replication. Factors which support this view include the emphasis on local community
      involvement, the low cost of external inputs, the well-established local NGO partner,
      Ministry of Health support, and the presence of a rural-based, community-orientated funding
      organization with a substantial international funding base and a long-term commitment to
      extending the scope of its activities in Zimbabwe. Descriptions of the principal intervention
      elements are contained in separate documents attached to this proposal.

      Objectives of the Study

      The principal objectives of the study are as follows:

        1. To scientifically evaluate the impact and cost-effectiveness of a combined behavioural
           and STD-control intervention strategy to slow the spread of HIV infections in rural
           Zimbabwe; and

        2. To extend recent monitoring of the demographic impact of the HIV epidemic in a rural
           area of Zimbabwe.

      Subsidiary aims include validation of innovative methods for data collection on HIV, other
      STDs - ie: using saliva samples [35] - and sexual behaviour in rural settings (all subject to
      final pre-test in the pilot study) and for estimating HIV incidence from cross-sectional
      prevalence data [27]; evaluation of antenatal clinic data as a source of information on HIV
      levels within the general population; and development of methods for routine evaluation of
      community-owned support programmes for individuals and families affected by heightened
      experience of chronic morbidity and mortality.

      Methodology

      Experimental Design for the Intervention Trial

      Six pairs of sub-communities (clusters), matched for similar levels of key factors affecting
      the spread of HIV, will be identified in the vicinity of the Honde Valley. Four of these
      pairs are likely to be within commercial estates - tea, coffee, forestry and orchards - and
      two in communal farming areas. Each sub-community will be chosen so that it includes a health
      clinic where improved STD services can be made available. The behaviour and STD-control
      intervention will be introduced in one cluster within each pair on a phased basis over a
      period of twelve months - ie: one new cluster every two months. In each case, a baseline
      survey for the evaluation will be conducted in the intervention and comparison clusters in
      the two-month period immediately prior to the introduction of the programme. For the
      evaluation, 1,000 respondents will be enrolled within a sector of each sub-community
      following an initial household census - half of those enrolled will be men aged 17-49 years
      and half will be women aged 15-39 years. Individuals who usually reside in the household will
      be eligible for full participation in the study - i.e.: recruitment will be on a de jure
      basis - in order to increase follow-up and reduce within-group heterogeneity. Within a
      household, the random selection process used will avoid instances where a husband and wife or
      more than one wife are enrolled and thereby reduce correlation of outcomes within individual
      clusters. Respondents in each pair of clusters will be surveyed again two years months after
      the baseline visit. Records will be kept on an anonymous basis but a mechanism will be put in
      place to enable the data to be linked within and between survey rounds.

      Outcome indicators will include knowledge about HIV and AIDS, sexual behaviour indicators -
      partner acquisition and partnership duration, mixing patterns and condom use - incidence of
      HIV and selected STD infections, and health-seeking behaviour indicators. Sample sizes were
      calculated to give an 80% power at the 95% significance level, comparing the matched
      intervention and comparison clusters, for a range of different outcome variables. The
      formulae used in these calculations take account of possible between-cluster and - in the
      case of prevalence - within-cluster variability [22,28]. Given the level of spatial mobility
      which exists within the Honde Valley area, some diffusion effect is likely to be present.
      This has been reflected in the sample size computations through the use of conservative
      anticipated excess reductions in the intervention clusters. We estimate that a sample size of
      1,000 individuals per cluster will yield a minimum of 700 observations, after accounting for
      loss to follow-up. In the case of the HIV incidence calculations, these observations will
      provide 1,120 susceptible person-years of observation, after allowing for a baseline
      prevalence in the general adult population of 20%. Under these conditions, an initial sample
      size of 1,000 per cluster should be sufficient to permit detection of a 40% excess reduction
      in HIV incidence, given a baseline annual incidence of 2% or higher. This sample size should
      also enable us to detect, inter alia, a 40% lower incidence of new HSV2 and trichomoniasis
      cases among individuals not infected at baseline and a 40% reduction in reported casual
      relationships without the use of condoms, given a baseline prevalence of 10% or over.
      Evidence from model simulations and empirical studies suggests that the excess reduction in
      HIV incidence required is plausible given a combined intervention strategy [19,29].
      Furthermore, the required excess reductions in STDs and high-risk behaviour should be
      attainable. Reductions in these factors, of the order indicated, would, if demonstrated,
      represent strong indirect evidence that the intervention strategy is slowing the spread of
      HIV infections. Reduction in other STDs would be a significant benefit, in itself, given the
      morbidity and adverse fertility consequences they frequently cause.

      Data Collection: Quantitative and Qualitative Methods

      Quantitative data will be collected on the intervention trial outcome measures summarized
      above, principally through the two-round survey. A cohort of participants for this survey
      will be recruited in a household census within each of the twelve study areas. The second
      round of the study will be conducted two years after the first visit in each area and will
      involve a repeat household census and further detailed interviews with the original
      participants. The population-based survey will also provide data on process indicators,
      including measures of contact with the intervention programme - eg: numbers of meetings
      attended and visits received from programme personnel - and utilization of programme services
      - eg: free condoms, revolving loans, care support, STD diagnosis and treatment - and other
      potential determinants of key outcomes, including socio-economic and demographic factors, and
      personal experience of HIV-related morbidity and mortality. Data will be collected on
      demographic indicators - eg: age- and gender-specific mortality, recent fertility, orphanhood
      and household composition - in the household and individual interviews, using standard
      demographic methods [30,31]. Quantitative data will also be collected on HIV prevalence at
      antenatal clinics, so that the representativeness of data from this source can be evaluated.
      Qualitative data on sexual and health-seeking behaviour and obstacles to behaviour change
      will be collected in focus-group discussions, pocket-chart voting sessions and key-informant
      interviews [32,33] and employed to aid questionnaire design and validation and in
      interpretation of statistical results. These methods were used successfully in our previous
      study [7]. However, to strengthen this aspect of the current proposal, additional input on
      the design and implementation of appropriate ethnographic methods will be received from a
      collaborator from the LSE (Dr. Campbell).

      Steps will be taken to develop the good working relationship already formed with the Honde
      Valley community, to mobilize community support for the research and provide reassurance that
      information given will be treated as strictly confidential. Thus, we hope to achieve high
      participation and follow-up rates and more reliable information. Preliminary meetings will be
      held with community leaders to explain the purpose of the study and the research procedures.
      Similar information will be given to each prospective participant prior to their decision on
      enrolment. Data collection methods such as self-completion questionnaires - 96% and 45% of
      women aged under 50 years, living in the Honde Valley, have received primary and secondary
      education, respectively, and literacy levels among men are higher than those for women [7] -
      and secret balloting, which avoid the need for participants to reveal personal information to
      enumerators directly and thus reduce under-reporting of sensitive information [34], have been
      field-tested and will be pre-tested further in the pilot study and used where feasible.
      Similarly, the possibility of using less invasive media such as saliva, urine or blood spot
      samples for HIV and STD testing is being investigated with the Public Health Laboratory in
      Harare [35]. The reliability and acceptability of these methods as applied in rural settings
      will also be field-tested in the pilot study.

      Questionnaires will be translated into the local Manyika dialect of Shona, back-translated
      and pre-tested in the pilot study. Data entry and validation will be undertaken using
      SPSS-PC+. Appropriate data entry forms will be designed for each section of the survey
      questionnaires and skip-rules, range checks etc will be employed to reduce data entry errors.
      BRTI/Blair staff have considerable experience of using SPSS-PC+ for data entry.

      Data Analysis: Scope and Methods

      Reliability and validity checks will be conducted to assess the quality of the quantitative
      data [36]. Data analysis will be conducted using statistical software - eg: STATA and SAS -
      and mathematical models of HIV incidence, which are based on underlying biomedical,
      behavioural and demographic determinants of HIV infections [37,38]. Statistical analyses will
      include tests for the significance of differences arising between paired intervention and
      control clusters [39,40] and tests for impact of contacts with the intervention programme and
      other possible determinants on changes in reported behaviour. The impact of the HIV epidemic
      on mortality will be monitored using longitudinal survey data and official vital registration
      records. Impact on fertility will be assessed by comparing birth rates among infected and
      uninfected individuals, controlling for other key determinants including age, education,
      religion and history of STDs. Crude birth rates, crude death rates and levels of natural
      population increase will be estimated from the survey data and the trends evaluated [12].
      Coverage and impact of care/support interventions will be investigated. HIV prevalence
      estimated from the population-based survey will be compared with estimates from women
      attending antenatal clinics to assess the representativeness of the latter. Adjustments will
      be made in data analysis for the matched-pair design of the study. Data from the study will
      be used to evaluate new methods for estimating incidence from cross-sectional HIV prevalence
      surveys [27].

      Ethical Considerations

      Informed consent will be sought as a condition for enrolment in the study. This will be in
      written form wherever literacy levels allow - which is expected to be in the great majority
      of cases. A written statement in the local dialect of shona will be provided explaining the
      purpose of the study and all aspects, benefits and risks of participation. The statement will
      make it clear that participants have the right to withdraw from the study at any time. Time
      will be allowed for prospective participants to read the statement, to ask questions and
      consider their decision. The statement will be read aloud to prospective participants who are
      unable to read themselves. Enumerators will be trained to do this in a balanced manner so as
      to avoid possible coercion.

      Participants will be given the opportunity to receive HIV-1 test results. Preliminary
      counselling will be offered during study interviews. Where participants indicate that they
      would like to be advised as to their own HIV-1 serostatus, appointments will be arranged for
      them to visit a local clinic where a free counselling and testing service will be made
      available. Standard Ministry of Health and Child Welfare and WHO procedures will be followed
      throughout, with further serological tests being undertaken as required.

      Participants who test positive for other sexually transmitted diseases will be advised of
      their results and a free treatment service will be offered wherever possible (eg: for
      trichomoniasis). Less invasive media such as urine and saliva will be used for the collection
      of samples for HIV-1 and STD testing. Where blood samples are sought, blood spots rather than
      venipuncture will be used. Appropriately qualified and trained personnel will be employed to
      collect the samples.

      Rigorous procedures will be maintained throughout the study to ensure full confidentiality of
      information obtained from participants. Data protection and anonymization procedures will be
      implemented and computerized matching methods will be used to ensure that access to linked
      data will be strictly limited to the principal investigators only, with the single exception
      that appropriate medical staff will be given access to results of HIV-1 or STD tests where
      participants wish to be informed of their results or to be offered treatment. The procedures
      will be such that staff, study participants and other individuals are not able to deduce
      individual HIV-1, STD and sexual behaviour details by applying exclusion and inclusion
      criteria. Confidential voting methods will be employed in the collection of sexual behaviour
      information so as to avoid the need for participants to impart personal information to
      enumerators.

      Benefits to participants will include participation in prevention, care and support
      activities in the intervention areas (see separate description of intervention activities).
      Subject to confirmation that these activities are effective, the researchers and programme
      managers are committed to ensuring that similar programmes will be introduced within each
      control area two years after the study is initiated in that area. In all areas, participants
      will be offered free treatment of STDs identified in the survey. Free information sheets on
      HIV-1 infection and AIDS which address gaps in information identified in the earlier study in
      Honde Valley will be made available to study participants in all areas during the baseline
      survey. Risks of participation in the research team or as a community member are believed to
      be low. Rigorous procedures are to be followed to avoid needle-stick injuries and to ensure
      confidentiality of information obtained, standard treatments will be offered for STDs
      diagnosed and established tests and associated procedures, which have proved to be very
      reliable in Zimbabwean settings, will be used for HIV-1 diagnosis, in particular, where
      results are to be made available to participants.

      Dissemination of study results will be done through the Biomedical Research and Training
      Institute (BRTI) and Blair Research Institute with approval from the Ministry of Health and
      Child Welfare. An original copy of the data set from the study will remain in Zimbabwe at
      BRTI and/or Blair. Approval for the study will also be obtained from the Central Oxford
      Research Ethics Committee in the United Kingdom prior to implementation.

      Personnel, Workplan and Location of Project Activities

      Dr. Gregson will manage and co-ordinate the proposed research project with expert
      epidemiological and statistical support from the Blair Research Institute in Harare and the
      Wellcome Trust Centre for the Epidemiology of Infectious Disease, at Oxford University (Dr.
      Chandiwana, Professor Anderson, Dr. Garnett and Dr. Donnelly), social psychology and
      ethnographic support from BRTI, the London School of Economics and the University of Natal
      (Mr. Tom Zhuwau, Dr. Cathy Campbell, Professor Eleanor Preston-Whyte and Professor Linda
      Richter), and biomedical support from BRTI (Professor Mason and Mr. Ocean Tobaiwa). Within
      the team we have considerable management and administrative as well as research experience
      and in a previous project we demonstrated the ability to develop and conduct a successful
      fieldwork-based scientific research project, given the level of technical and logistical
      support envisaged in this proposal. Zimbabwe has a good supply of well-qualified personnel in
      most disciplines and staff with appropriate sociological, demographic and/or medical
      expertise will be recruited. All staff will be given in-depth training in the specific
      requirements of the study. A summary schedule of project activities over time is attached.

      Intended Use of Results

      The results will be disseminated through seminars, workshops and publications in local and
      international journals. In these ways, we will seek to promote greater awareness of the level
      of effectiveness of the intervention strategy evaluated in the given context.
    

Intervention name(s): Peer education among commercial sex workers and clients; Condom distribution and promotion; Syndromic treatment of sexually transmitted infections; Systemic counselling for STI patients
Intervention type(s): Behavioral; Behavioral; Procedure; Procedure
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: HIV prevention; Zimbabwe; Core groups; Peer education; Syndromic management; Commercial sex workers; Condom distribution; HIV Seronegativity