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EPIDEMIOLOGY AND SOCIAL SCIENCE

Can Highly Active Antiretroviral Therapy Reduce the Spread

of HIV?A Study in a Township of South Africa

Bertran Auvert, MD, PhD,* Sylvia Males, Adrian Puren, MD, PhD, Dirk Taljaard, Michel Carael, PhD,# and Brian Williams, PhD**

Background: Calls have been made for the large-scale delivery of highly active antiretroviral therapy (HAART) to people infected withHIV in developing countries. If this is to be done, estimates of the

number of people who currently require HAART in high HIV preva-lence areas of sub-Saharan Africa are needed, and the impact of thewidespread use of HAART on the transmission and, hence, spread of HIV must be assessed.

Objectives: To estimate the proportion of people eligible for com-bination antiretroviral therapy and to evaluate the potential impact of providing HAART on the spread of HIV-1 under World Health Or-ganization (WHO) guidelines in a South African township with a highprevalence of HIV-1.

Design: A community-based cross-sectional study in a townshipnear Johannesburg, South Africa, of a random sample of approxi-mately 1000 men and women aged 15 to 49 years.

Methods: Background characteristics and sexual behavior were re-corded by questionnaire. Participants were tested for HIV-1, and their CD4 + cell counts and plasma HIV-1 RNA loads were measured. Theproportion of people whose CD4 + cell count was less than 200cells/mm 3 and who would be eligible to receive HAART under WHOguidelines was estimated. The potential impact of antiretroviral drugson the spread of HIV-1 in this setting was determined by estimatingamongthe partnerships engaged in by HIV-1positive individuals the

proportion of spousal and nonspousal partnerships eligible to receiveHAART and then by calculating the potential impact of HAART onthe annual risk of HIV-1 transmission due to sexual contacts withHIV-1infected persons. The results were compared with those ob-

tainedusing UnitedStates Department of Healthand Human Services(USDHHS) guidelines.

Results: The overall prevalence of HIV-1 infection was 21.8%(19.2%24.6%), and of these people, 9.5% (6.1%14.9%) or 2.1%(1.3%3.3%) of all those aged 15 to 49 years would be eligible for HAART (ranges are 95% confidence limits). In each of the next 3years 6.3% (4.6%8.4%) of those currently infected with HIV-1 need to start HAART. Among the partnerships in which individuals wereHIV-1positive, only a small proportion of spousal partnerships(7.6% [3.4%15.6%]) and nonspousal partnerships (5.7%, [3.0% 10.2%]) involved a partner with a CD4 + cell count below 200cells/mm 3 and would have benefited from the reduction of transmis-sion due to the decrease in plasma HIV-1 RNA load under HAART.

Estimates of the impact of HAART on the annual risk of HIV-1 trans-mission show that this risk would be reduced by 11.9% (7.1% 17.0%). When using USDHHS guidelines, the proportion of HIV-1 positive individuals eligible for HAART reached 56.3% (49.1% 63.2%) and the impact of HAART on the annual risk of HIV-1transmission reached 71.8% (64.5%77.5%).

Conclusions: Thepopulation impact of HAART on reducing sexualtransmission of HIV-1 is likely to be small under WHO guidelines,and reducing the spread of HIV-1 will depend on further strengthen-ing of conventional prevention efforts. A much higher impact of HAART is to be expected if USDHHS guidelines are used.

Key Words: HAART, HIV, South Africa, CD4 + , viral load, trans-mission

(J Acquir Immune Defic Syndr 2004;36:613621)

Sub-Saharan Africa remains the region most severely af-fected by HIV/AIDS. Approximately 3.4 million new in-fections occurred in 2001, bringing the total number of peopleliving with HIV/AIDS in this region to 28.1 million. In SouthAfrica, the prevalence of HIV-1 infection is among the highestin the world, with almost 1 in 9 South Africans living withHIV/AIDS. 1

Received for publication July 1, 2003; accepted November 26, 2003.From *INSERM U88IFR 69, Saint-Maurice, France; AP-HP, Hopit al

Ambroise Pare, Boulogne-Billancourt, France; Universite de Versailles,Saint-Quentin-en-Yvelines, France; UFR medicale Paris, Ile-de-France Ouest, Garches, France; National Institute for Communicable Diseases,Johannesburg, South Africa; Progressus CC, Johannesburg, SouthAfrica; #UNAIDS, Geneva, Switzerland; and **16 rue de la canonnire,Geneva, Switzerland.

Supported by the Agence Nationale de Recherche contre le SIDA (ANRS-2002-1265), Paris,France; NationalInstitute for Communicable Diseases,Johannesburg, South Africa; and Institut National de la Sante et de laRecherche Medicale, Paris, France.

Reprints: Bertran Auvert, INSERM U88, 14, rue du Val dOsne, 94415 Saint-Maurice Cedex, France (e-mail: bertran.auvert@paris-ouest .univ-paris5.fr).

Copyright 2004 by Lippincott Williams & Wilkins

J Acquir Immune Defic Syndr Volume 36, Number 1, May 1 2004 613


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In developed countries, striking improvements havebeen reported in the health status and life expectancy of HIV-infected patients as a result of the widespread use of antiretro-viral therapy (ART). 2 10 Ninety percent of people infected with HIV live in the developing world, however, where only

4% of those who need ART currently have access to the drugsthey require. 11 Several studies have evaluated the feasibility of delivering ART to patients in resource-limited settings, 12,13

but despite international pressure to implement highly activeantiretroviral therapy (HAART) in such countries, treatmentrequirements have yet to be precisely characterized. In devel-oping countries with high HIV prevalence, such as South Af-rica, the fraction of the population that would be eligible for HAART under World Health Organization (WHO) guide-lines 11 is not precisely known. It is also not known how thisfraction will change if the United States Department of Healthand Human Services (USDHHS) guidelines 14 are used. Suchinformation is needed to calculate the cost of scaling up ARTand to prepare health systems to deliver these treatments. Inaddition, the potential impact of the widespread use of antiret-roviral drugs on the spread of HIV remains unclear and re-quires evaluation. There are biologic and epidemiologic rea-sons to believe that ART will reduce sexual transmission of HIV. Biologic studies have shown that antiretroviral drugs de-crease HIV in seminal fluid 15 and in cervicovaginal secre-tions. 16 An epidemiologic study of discordant couples hasshown that the use of zidovudine by infected men was associ-ated with a 50% reduction in the risk of transmission of HIV totheir female sexual partner, 17 suggesting that the wide use of HAART would slow down the spread of HIV in the countries

where the route of transmission is mainly heterosexual.The objectives of this study are to estimate the propor-

tion of the population needing HAART in a township in SouthAfrica under WHO guidelines, to estimate the short-term im-pact of providing ART on the spread of HIV, and to assess theimpact of using USDHHS guidelines on these estimations.

MATERIALS AND METHODS

SurveyIn April 2002, a population-based cross-sectional study

was conducted in a township 40 km south of Johannesburg,

South Africa. Households were selected by a 2-stage randomsampling technique. Index houses were randomly selected from a map obtained from the local municipal offices. Usingeach index house as a starting point, a cluster of householdswas identified by starting to the right of the index house and counting households around the street block and adjacentstreet blocks until 50 households had been reached. A self-weighting random sample of 20 households was then chosenfromeachcluster. All men and women aged 15to 49 years whoslept in the selected households the night before the study

team s visit were eligible for inclusion in the study. The con-sent form was presented in the language of the respondent,who was invited to take part in the study, and those who agreed were asked to sign the consent form. The response rate was68%. Eligible participants were transported to a local facility

for the interviews and the collection of blood and urinesamples. If eligible participants were not at home, the studyteam made up to 3 repeat visits on different days at differenttimes. The field work was done in the late afternoon, whenresidents returned from work, so as to reach as many residentsas possible.Field work wasconductedon Monday to Thursdayand again on Saturday to ensure that people who work duringthe week could be reached. When it was not possible for par-ticipants to go directly to the interviewing points or for house-hold members whowere nothome, appointmentswere made attimes that suited the participants, and these appointments werefollowed up.

The questionnaire used in this study was based on aUNAIDS questionnaire. 18 The interviewers completed thequestionnaire during a private interview in the preferred lan-guage of the interviewee. Data were collected on background and behavioral characteristics. Sexual partners were divided into spousal and nonspousal partners. The spousal partnerswere partners to whom the respondents were married or lived with as married. The nonspousal partners were all the other partners. The questionnaire allowed for a detailed descriptionof all the nonspousal partners during the last 12 months,including those with whom the respondent had only 1 sexualcontact. In addition, specific questions were asked about theuse of condoms during the last months with nonspousal

partners.During the survey, participants with symptoms of sexu-

ally transmitted infections (STIs) were encouraged to go to thelocal STI clinic for treatment. Participants who wished toknow their HIV status were offered a separate free enzyme-linked immunosorbent assay (ELISA) test with pre- and post-test counseling to be arranged through the normal clinicalchannels. Blood samples were tested for syphilis, HIV-1,CD4 + count, and plasma HIV-1 RNA load. Urine sampleswere tested for chlamydial infection.

When results were available, a trained nurse delivered the syphilis and Chlamydia infection test results directly to theparticipants. Participants with positive STI results were en-couraged to seek treatment at the local STI clinic. Individualswith fewer than 200 CD4 + cells/mm 3 were included in a spe-cific program that involved voluntary counseling and testing,prevention of opportunistic infections, and access to ART.Pregnant women were informed of the possibility of reducingthe mother-to-child transmission (MTCT) of HIV-1 duringpregnancy and childbearing. The cost of transportation tohealth facilities where the MTCT program was available freeof charge was borne by the study.

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Laboratory ProceduresFollowing the interview, trained nurses collected whole

blood and urine (first flow) samples. The urine samples werestored at 4 C and then transported the next day to the labora-tory, where they were stored at 70C before being analyzed.

Two EDTA blood tubes of 20 mL of venous blood were takenand transported at room temperature to the laboratory the fol-lowing morning. One tube was centrifuged at 400 g for 10 min-utes, and 5 aliquots of plasma were then taken and frozen at70C. The second tube of blood was used to determine theCD4 + count.

An ELISA screen (Genscreen HIV1/2; version 2, Bio-Rad, France and Wellcozyme HIV recombinant; Abbott Mu-rex, Dartford, UK) and ELISA confirmation (Vironostika HIVUni-Form II plus O; BioMerieux, Boxtel, Netherlands) werecarried out on plasma to test for HIV-1 infection.

Plasma HIV-1 RNA load was determined by reverse-transcription polymerase chain reaction (PCR) using an assaydesigned to detect all M-group subtypes (Amplicor HIV-1Monitor Test,version 1.5;RocheDiagnostic Systems, Branch-burg, NJ). 19

CD4 + cell counts were determined by BD FACSOUNTanalysis (BD Biosciences, Belgium).

Syphilis testing was performed using a rapid plasma re-agin (RPR) screen (Macro-Vue RPR Card Tests;BectonDick-inson Microbiology Systems, Cockeysville, MD), followed bya fluorescent treponemal antibody absorption (FTA-ABS)confirmatory test (FTA-ABS Test Sorbent; BioMerieux,France). A positive RPR (at any titer) and FTA-ABS weretaken as evidence of recently acquired and/or untreated syphi-lis. Urine samples were tested for Chlamydia infection using aqualitative DNA amplification method (Amplicor CT/NGTest; Roche Diagnostic Systems).

EthicsEthical clearance was obtained from the University of

Witwaterstrand Committee for Research on Human Subjectson February 8, 2002 (protocol study no. M020103).

Data ManagementLaboratory results and data generated from question-

naires were entered twice into a database (Microsoft Access,Redmond, WA) by different people. The 2 entries were com-

pared, and discrepancies were corrected. The data werechecked for inconsistencies. The files were then imported intothe Statistical Package for Social Sciences (SPSS 8.0 for Win-dows, Chicago, IL) and prepared for statistical analysis.

Statistical MethodsEstimation and Statistical Tests

The Clopper-Pearson method, which is known to pro-duce slightly conservative 2-sided confidence intervals, 20 was

used to estimate confidence limits of proportions. (Unless oth-erwise stated, ranges give 95% confidence limits.) Medians of quantitative data were calculated with their interquartile range(IQR). Quantitative data were compared between subgroupsusing the Kruskal-Wallis test. The correlation between plasma

HIV-1 RNA load and CD4+

count was analyzed using thenon-parametric Spearman correlation coefficient and by regressionof log 10 of the plasma HIV-1 RNA load against the CD4

+

count.

Estimation of the Proportion of the Population NeedingHAART Under WHO Guidelines

Current WHO recommendations are that all patientswith CD4 + counts below 200 cells/mm 3 should be offered ART, 11 and we used this criterion to estimate the proportion of the 15- to 49-year-olds in that population currently requiringHAART. To estimateconservativelythe proportion needing tostart HAART in the next 3 years, we assumed that the CD4 +

cell counts decline by an average 50 cells/mm3

/y in untreated infected subjects. 2124 As a result, the proportion of the 15- to49-year-old population needing to start HAART in the next 3years under WHO guidelines was determined by the propor-tion of the sample with CD4 + counts in the range of 201 to 350cells/mm 3 .

Estimation of the Impact of HAART on the Short-TermSpread of HIV-1 Under WHO Guidelines

Assuming that allpeoplewith CD4 + cell counts less than200/mm 3 receive HAART, we used 2 approaches to estimatethe short-term impact of providing HAART on the spread of HIV-1. The first approach assumes that any HIV-1positive

personreceiving HAART will becomeless infectious. We thuscalculated among partnerships engaged in by HIV-1positiveindividuals the proportion of spousal and nonspousal partner-ships eligible to receive HAART and, as a consequence, thetransmission of HIV-1 that could be reduced by HAART. Inthe second approach, we used data on the annual risk of HIV-1transmission as a function of plasma HIV-1 RNA load from astudy in Uganda 25 to estimate the potential number of newHIV-1 infections per year per HIV-1infected person. Fromthis, we estimated the relative decrease in the annual risk of HIV-1 transmission assuming that HAART reduces plasmaHIV-1 RNA load to fewer than 400 copies/mL. This approachallows for the contribution to the spread of HIV-1 by individu-

als with low CD4+

counts, who are more likely to have highplasma HIV-1 RNA loads.

Impact of Using USDHHS GuidelinesTo assess the impact of using USDHHS guidelines on

the proportion of the population requiring HAART, we recal-culated this proportion using USDHHS guidelines recom-mending initiation of HAART with CD4 + counts below 350cells/mm 3 or a plasma HIV-1 RNA load above 55,000copies/mL. 14 The impact of HAART on the short-term spread

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of HIV-1 under USDHHS guidelines was estimated as de-scribed previously.

RESULTS

Background Characteristics andSexual Behavior

Most households have electricity (89.0% [85.8% 91.6%]) and piped water (88.2% [84.9% 90.8%]), but flushtoilets are less common (31.2%, [27.2% 35.6%]). The median(IQR) of the combined monthly income per household is 884(500 1500) South African Rands, corresponding to about 88(50 150) Euros. The median (IQR) number of persons per household is 4 (3 5), and the median (IQR) number of personsper room is 1.4 (1 2).

A total of 930 people agreed to participate in the survey.The male-to-female ratio was 1:1.12. Background characteris-tics of the sample are given in Table 1. At the time of the in-

terview, 90.9% (88.8% 92.6%) of all participants reported having ever had sex. Among those who had experienced sex-ual intercourse, 34.7% (31.5% 38.0%) said that they had never used a condom. Among men and women who had expe-rienced sexual intercourse, 68.7% (63.8% 73.2%) and 48.6%(43.9% 53.3%), respectively, reported having had at least 1nonspousal sexual partner in the last 12 months. Among menand women who were married or living as married, the corre-sponding figures were 32.6% (24.9% 41.3%) and 11.7%

(7.8% 17.0%), respectively. Among those who had had sex inthe last month with nonspousal partners, 39.2% (33.5 45.3%)reported that they always used condoms.

Prevalence of HIV-1, Syphilis, and

Chlamydial InfectionsThe overall prevalence of HIV-1 infection was 21.8%(19.2% 24.6%): 17.4% (14.1% 21.4%) among men and 25.7% (range: 21.9% 30.0%) among women. The highestprevalence of HIV-1 by age was 34.4% (19.2% 53.2%)among men aged 35 to 39 years and 46.4% (34.4% 58.7%)among women aged 25 to 29 years. The median age of HIV-1 infected people was 31 (IQR: 26 37) years for men and 23(IQR: 19 32) years for women. Among those having a spousalpartnership and those having a nonspousal partnership, theprevalence of HIV-1 was 25.6% (21.1% 30.7%) and 23.8%(20.1% 27.9%), respectively. The prevalence of syphilis was3.2% (1.9% 5.4%) for men and 9.6% (7.4% 12.8%) for

women. The prevalence of Chlamydia infection was 6.2%(4.3% 8.9%) for men and 6.9% (5.0% 9.6%) for women.

Distribution of Plasma HIV-1 RNA LoadThe median (IQR) plasma HIV-1 RNA load was 55,750

(10,750 172,000) copies/mL (4.7 [4.0 5.2] copies/mL log 10 ), and the difference between men and women was notsignificant ( P = 0.59 by Kruskal-Wallis test). The median(IQR) plasma HIV-1 RNA load in participants with CD4 +

counts less than 200 cells/mm 3 was 160,000 (72,900 410,000)copies/mL (5.2 [4.9 5.6] copies/mL log 10 ), and in partici-pants with CD4 + counts higher than 200 cells/mm 3 , it was sig-nificantly lower at 46,800 (9407 149,500) copies/mL (4.7

[4.0 5.2]) copies/mL log 10 ) (P = 0.000 by Kruskal-Wallistest).

Distribution of CD4 + CountsThe median (IQR) CD4 + cell count in the HIV-1

negative and positive participants was 1128 (911 1371)cells/mm 3 and 475 (321 735) cells/mm 3 , respectively, and thedifference was statistically significant ( P = 0.000 by Kruskal-Wallis test). Among HIV-1 negative men, the median (IQR)CD4 + cell count was 1057 (850 1316) cells/mm 3 , and amongwomen, it was slightly higher at 1180 (963 1436) cells/mm 3

(P = 0.000 by Kruskal-Wallis test). Among HIV-1 positiveparticipants, the median CD4 + count was 488 (321 740)

cells/mm3

and not statistically different between men and women ( P = 0.17 by Kruskal-Wallis test). The distribution of CD4 + cell counts in HIV-1 infected individuals is given inFigure 1.

Characteristics of HIV-1Infected SubjectsEligible for Antiretroviral Therapy UnderWHO Guidelines

Taking a CD4 + cell count of 200cells/mm 3 as the criticallevel for the initiation of HAART, 9.5% (6.1% 14.9%) of

TABLE 1. Background Characteristics of Men and Womenincluded in the Survey

Men(n = 438)

Women(n = 492)

Total(n = 930)

Median age (IQR) years 25 (19 33) 28 (20 37) 26 (20 35)Ethnic group (% in each

category)Sotho 33.8 36.6 35.3Tswana 7.5 6.5 7.0Xhosa 9.6 13.0 11.4Zulu 36.8 35.4 36.0Other 12.3 8.5 10.3

Primary schoolcompleted (%) 84.5 83.3 83.9

Occupation (% in eachcategory)

Employed 37.4 25.0 30.9Student 29.9 22.2 25.8Unemployed 27.6 50.2 39.6Other 5.0 2.6 3.8

Marital status (%)Married or living

as married 30.8 41.9 36.7Single 69.2 58.1 63.3




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HIV-1 infected people, or 2.1% (1.3% 3.3%) of 15- to 49-year-olds, should be provided with HAART. The median age

of these people was 33 (IQR: 26 36) years, with a male-to-female ratio of 1:2.2. Of these persons, 36.8% (20.4% 73.9%)were married and 47.4% (25.2% 70.5%) reported at least 1nonspousal sexual partner in the last 12 months.

At the time of the study, 18.9% (13.8% 25.2%) of HIV-1 infected people had CD4 + cell counts between 200 and 349cells/mm 3 such that 6.3% (4.6% 8.4%) of those currently in-fected with HIV-1, or 1.4% (0.97% 1.9%) of 15- to 49-year-olds, should start HAART in each of the next 2 years.

On average, plasma HIV-1 RNA load in copies/mL log 10 falls by a factor of 1.43 (1.32 1.56) for each 100cells/mm 3 decline in CD4 + count, as shown in Figure 2. Thereis substantial dispersion in the data, however, and a high pro-

portion of individuals have a high plasma HIV-1 RNA load even though their CD4 + cell count is above 200 cells/mm 3 .

Impact of HAART on the Short-Term Spread of HIV-1 Under WHO Guidelines

Among spousal partnerships involving HIV-1 positiveindividuals, 7.6% (3.4% 15.6%) had a CD4 + cell count below

200 cells/mm 3 . Of the nonspousal partnerships in the last 12months involving HIV-1 positive individuals, 5.7% (3.0% 10.2%) had a CD4 + cell count below 200 cells/mm 3 . Of thespousal and nonspousal partnerships in the last 12 months en-gaged in by HIV-1 positive individuals, a total of 6.3%

(3.8% 9.6%) had a CD4+

cell count below 200 cells/mm3

The plasma HIV-1 RNA load stratified by CD4 + cellcount is given in Table 2. Combining the survey data from thepresent study with data on the annual risk of infection from astudy in Uganda, 26 we are able to estimate the probability that1 current infection will give rise to a secondary infection in 1year (annual risk of HIV-1 transmission). By assuming thatthose who receive HAART cease to be infectious, we alsoshow in Table 2 that the provision of HAART to all infected subjects with a CD4 + cell count below 200 cells/mm 3 will re-duce the annual risk of HIV-1 transmission by 11.9% (7.1% 17.0%).

Impact of Using USDHHS GuidelinesIf HAART were given to individuals with a CD4 + cell

count below 350 cells/mm 3 or a plasma HIV-1 RNA load greater than 55,000 copies/mL, more people would need HAART and the impact on the short-term spread of HIV-1would be greater. If this were done, we estimate (data notshown) that 56.3% (49.1% 63.2%) of people infected withHIV-1 would have required HAART at the time of the study.As a result, 50.0% (39.5% 60.5%) of spousal and 59.3%(52.0% 66.2%) of nonspousal partnerships would potentiallybenefit from the resulting reduction of transmission, and theannual risk of HIV-1 transmission would be reduced by 71.8%

(64.5% 77.5%).

DISCUSSION

Number of People Who Need HAARTMarked improvements have been reported in the health

status and life expectancy of HIV-1 infected individuals and coincide with the widespread use of antiretroviral drugs. 2 10 Itis estimated that only 230,000 HIV-infected people in poor and middle-income countries are currently being treated with ARTand that half of these people live in Brazil. In sub-Saharan Af-rica, where 70% of the HIV-1 infected people live, almost noor limited triple-combination HIV-1 treatment is used. 24 Sev-

eral studies have investigated the feasibility and efficacy of ART in resource-poor settings and confirm that antiretroviraldrugs can be successfully provided in developing coun-tries. 12,13 Treatment requirements have not been well charac-terized in sub-Saharan countries, however. The current com-munity-based study was conducted in a South African town-ship of the Gauteng province with a very high prevalence of HIV-1. In this community, the prevalence of HIV and syphilisamong women that we found (9.6% and 25.7%, respectively)was comparable to the prevalence (31.6% and 6.0%, respec-

FIGURE 1. Distribution of CD4 + cell count among HIV-1 infected persons (with the upper limit of the 95% confidenceinterval).

FIGURE 2. Plasma HIV-1 RNA load by CD4 + count amongHIV-1positive individuals. The regression line is plasma HIV-1RNA load (copies/mL log 10 ) = 5.40 1.57 10 3 CD4 +

count (Spearman = 0.53, P = 0.000).




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tively) reported for the same province in the antenatal surveyconducted in 2002 by the South African National Departmentof Health. 27 We estimate that 9.5% of all adults infected withHIV-1, or 2.1% of those aged 15 to 49 years, would be eligiblefor antiretroviral drugs under WHO guidelines that recom-mend initiating HAART at CD4 + counts less than 200cells/mm 3 .

In addition, a further 6.3% of all adults infected withHIV-1, or 1.4% of those aged 15 to 49 years, should startHAART each year. Because HAART will reduce mortality,the number of individuals who need HAART will increase. Asdata on HAART coverage and survival of patients receivingHAART in Africa become available, it will be possible to es-timate more precisely the demand for HAART and the cost of providing it. 28,29 Although the empiric data provided by thisstudy represent an important first step, detailed public healthand economic studies of the feasibility of testing and treating

these individuals will allow for a precise estimate of the feasi-bility and cost of scaling up ART in settings with a high HIVprevalence. Such studies will make it possible to refine recentstudies that have attempted to estimate the real cost of an ef-fective response to the global AIDS epidemic. 30,31

Estimates of the fraction of the population needingHAART in sub-Saharan Africa depend on the natural historyof the epidemic and, in particular, on its magnitude and matu-rity. Because the epidemic in South Africa has developed re-cently but very rapidly, 1,32 this study should be repeated in

other sub-Saharan African settings, especially in countrieswhere the prevalence is lower and the epidemic is more matureand even declining. Nevertheless, it is unlikely that the propor-tion of HIV-positive people needing HAART will be dramati-cally different in other places in sub-Saharan Africa, where theepidemic is driven primarily by heterosexual contact. HIV-1has the same impact on the immune system, and the epidemichas probably reached an endemic state even in more recentlyaffected countries.

When using USDHHS guidelines, we found that a highproportion (more than 50%) of people infected with HIV-1would have needed HAART at the time of the study. The dras-tic difference found when using WHO and USDHHS guide-lines is due to the strong difference in our HIV-positive popu-lation between the fraction having CD4 + counts below 200cells/mm 3 (about 10%) and the fraction having a viral load above 55,000 copies/mL (about 50%). This indicates that the

proportion of people needing HAART critically depends onthe choice of guidelines applied. A recent study conducted inthe Rakai population in Uganda found that 20% of infected persons hadviral loads greater than 55,000 copies/mL and thusneeded to receive HAART under USDHHS guidelines. 33 Thereasons for such a difference when compared with our studyare unclear. It could be due to the difference in the samplecollection. Viral loads were determined from recently sampled plasma in our study and from archived serum in the Rakaistudy, and such variation in the collection and storage can at

TABLE 2. Estimates of the Potential Impact of HAART on the Annual Risk of HIV-1 Transmission

Total (6)

Plasma HIV-1 RNA load (copies/mL)

49,999 NA

Annual risk of HIV-1transmission(person/y)

0 0.04 0.12 0.14 0.23 NA

Percentage of HIV-1 positivepopulation (%)

3.1(1.1 6.5)

8.2(4.7 12.9)

12.2(8.0 17.7)

25.5(19.6 32.2)

51.1(43.8 58.2)

100

Weighted annual risk of HIV-1 transmissionwithout HAART (person/y)

0 0.00327(0.00188 0.00516)

0.0147(0.00960 0.0212)

0.0357(0.0274 0.0451)

0.118(0.101 0.134)

0.171(0.1591 0.183)

Percentage of HIV-1 positivepopulation withCD4 + counts >200cells/mm 3

3.1(1.1 6.5)

8.2(4.7 12.9)

12.2(8.0 17.7)

23.5(17.5 30.0)

43.4(36.3 50.6)

90.3(85.3 94.1)

Weighted annual risk of HIV-1 transmission

with HAART (person/year)

0 0.00327(0.00188 0.00516)

0.0147(0.00960 0.0212)

0.0329(0.0245 0.0420)

0.0997(0.0835 0.116)

0.151(0.136 0.165)

The table gives estimates of the annual risk of HIV-1 transmission as a function of plasma HIV-1 RNA load, 27 the proportion of the present population fallinginto each plasma HIV-1 RNA load band, the weighted annual risk of HIV-1 transmission, the proportion of the population that will not receive HAART under present guidelines, andthe weighted annualrisk of HIV-1 transmissionwiththe provisionof HAART.The decrease in theannual risk of HIV-1 transmissionfrom0.171/person/y without HAART to 0.151/person/y with HAART corresponds to a reduction of 11.9% (7.1% 17.0%).

NA, not applicable.




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least partly explain the difference between the 2 studies. 34 Thedifferencecould also be dueto thepopulationsample. We havedesigned a specific cross-sectional approach for our studycompared with the cohort used in the Rakai study.

Potential Impact of HAART on the Spreadof HIV

The impact that HAART might have on the spread of HIV by reducing the infectivity of treated subjects and pre-venting subsequent sexual transmission remains unclear. 35 Amathematic model suggested that the widespread use of anti-retroviral drugs could curb the HIV epidemic in a gay commu-nity in San Francisco. 36 A recently published stochastic simu-lation showed that in Uganda, using USDHHS guidelines,HAART will have a limited impact on the spread of HIV. 33

Here, we have used 2 indicators to evaluate the short-term im-pact of the widespread use of HAART on HIV-1 transmissionin a South African township where the prevalence of HIV-1 ishigh. The first indicator revealed that only a small proportionof spousal partnerships (7.6%) and nonspousal partnerships(5.7%) formed by HIV-1 infected individuals will potentiallybenefit from the likely reduction of transmission due to thedecrease in plasma HIV-1RNA load induced by HAART. Thesecond indicator suggests that the annual risk of HIV-1 trans-mission would be reduced by 11.9%. The low numeric valuesof the 2 indicators show that the impact of HAART on thespread of HIV, by reducing the infectivity of treated subjectsand preventing subsequent sexual transmission, will be smallunder WHO guidelines.

The first indicator takes into account the sexual activityof HIV-1 positive people in estimating the impact of HAARTon the spread of HIV-1. Nevertheless, this indicator does nottake into account that in a proportion of the partnerships of HIV-1 positive individuals, both partners could be HIV-1 positive. Therefore, this indicator is likely to be an overestima-tion of theproportion of sexual relationships that would benefitfrom the reduction of transmission due to the decrease inplasma HIV-1 RNA load by HAART. The second indicator was based on a study conducted in Uganda because of the lack of South African data on the relationship between HIV-1 viralload and sexual transmission of HIV-1. Therefore we cannotexclude that the result could have been slightly different if such

data were available.Because the average plasma HIV-1 RNA load only in-creases slowly as CD4 + count falls, the infectiousness of indi-viduals who are eligible for HAART is close to the infectious-ness of those who are not. As a result, we can estimate theimpact of HAART on the spread of HIV-1, as a first approxi-mation, by the proportion of HIV-1 positive people whowould receive HAART. This is confirmed by this study, where9.5% of HIV-1 infected people need HAART and the reduc-tion in transmission was estimated to be 11.9%.

Many people are not eligible for HAART because their CD4 + counts are above 200 cells/mm 3 even though they have ahigh plasma HIV-1 RNA load, and they will continue to con-tribute substantially to the spread of HIV after the introductionof HAART. In addition, individuals who are in the early

asymptomatic period and have a negative HIV test, that is,those who are newly infected or primary HIV-1 infected indi-viduals are not taken into account in the current study, and it isbelieved that they contribute substantially to the spread of HIVbecause of their high plasma HIV-1 RNA load. 37 This group islikely to be small, however, because the window period of theELISA HIV test used here is short.

Our estimation of the impact of HAART on the spread of HIV has been calculated assuming full coverage and thatHAART reduces plasma HIV-1 RNA load to


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(about 20%) in comparison to the proportion in the South Af-rican population of this study (about 50%).

Consequences for PreventionUnder WHO guidelines, the limited effect of even the

widespread use of HAART on the spread of HIV in sub-Saharan Africa found in this study suggests that HAART willnot substantially reduce the heterosexual spread of HIV. Scal-ing up HAART should not lead to any relaxation in preventionefforts to reduce the spread of HIV. In particular, we advocate,as others have, 49 that the budget allocated for preventionshould not be in competition with the budget allocated to treat-ment and should not be reduced. In this context, the preventionof HIV infection should be based on established cost-effectiveprevention strategies such as condom distribution, blood and injection safety measures, treatment of STIs, and changes of sexual behavior. 50

In the population under study here, the prevalence of both syphilis and Chlamydia is high, sexual risk behavior iscommon, and condom use is not optimal in nonspousal part-nerships, although it is higher than in some other cities of sub-Saharan Africa. 51 53 This situation, characterized by low con-dom use, high rates of curable STIs, and sexual risk behavior,is common in sub-Saharan Africa, and prevention efforts toreduce the spread of HIV need to be substantially strength-ened.

The development of HAART represents a major ad-vance in the fight against HIV/AIDS, and even thoughHAART has to be administered by trained health workers inhealth centers satisfying the minimum requirements for the de-livery of such drugs, 11 there is no doubt that HAART, which isalready available in some countries in sub-Saharan Africa suchas Senegal, 42 will soon become available in other countries.Theconsequencesof the availability of HAART on preventionare difficult to predict. HAART could facilitate HIV preven-tion. The targeted availability of an effective therapy could lead to an increase in demand for HIV testing and counseling,which has been shown to be effective in reducing risky sexualbehaviors in heterosexual couples, 35,54 and to a lessening of the stigma associated with AIDS. 13 HAART could also have anegative impact on prevention, however, because recent stud-ies in San Francisco and Amsterdam have provided evidenceof an increase in unprotected sex among men who have sex

with men, possibly due to the availability of HAART.11,55,56

Detailed studies conducted in sub-Saharan Africa on the im-pact on prevention of the widespread use of HAART will beneeded to judge adequately the complementary approaches of prevention and treatment of the HIV/AIDS epidemic in sub-Saharan communities highly infected by HIV.

ACKNOWLEDGMENTThe authors thank all the participants who agreed to take

part in the survey, to answer the questions we put to them, and

to provide blood samples. Special thanksgo to Reathe Taljaard and Gaph Pathedi, who helped to make the survey possible.Ewalde Cutler, Precious Magooa, Melody Nzama, MosesMashiloane, and Japh Sibeko from the National Institute for Communicable Diseases, Johannesburg, South Africa, pro-

vided excellent technical assistance in regard to the laboratorytesting. The authors thank Emmanuel Lagarde, INSERM U88,France, for his invaluable assistance and support.

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