Volume 2 Issue 3Fall 2004 SPOTLIGHT

n 2001, President Festus Mogaeintroduced an unprecedented ini-tiative to provide antiretroviral

(ARV) therapy free of charge to AIDS pa-tients in Botswana. At the time, 38.8% ofthe population was HIV-infected. Thecountry’s already overburdened health sys-tem, however, lacked the training, infra-structure and personnel to train the nation’shealthcare workers to administer the life-saving new drugs. The Harvard School ofPublic Health AIDS Initiative, through itspartnership with the Botswana governmentand support from the African Comprehen-sive HIV/AIDS Partnerships (ACHAP), de-veloped a pilot training program inHIV/AIDS care and ARV therapy. The pro-gram named “KITSO,” the Setswana wordfor knowledge, set out to provide innova-tive, high quality, sustainable HIV/AIDStraining, crafted specifically for Botswana’shealth professionals.

Local clinicians and internationalHIV/AIDS experts collaborated to developthe baseline training course, AIDS ClinicalCare Fundamentals. The course teacheshealthcare providers how to give standard-ized comprehensive care and treatment inBotswana’s national ARV program, MASA.A participant in a 2003 AIDS Clinical CareFundamentals course said, “The course hasprovided me with a large amount of ARV

therapy information. I am confident that Iwill go back to the work place fully knowl-edgeable and being in a position to help pa-tients on ARV therapy. Many of them werecoming to our clinics and I did not knowhow to help them, but now I do.”

To date, the KITSO AIDS Training pro-gram has conducted 44 training courses inAIDS Clinical Care Fundamentals, as well ascourses in Laboratory Fundamentals, Intro-duction to HIV, Biosafety & MASA, Medica-tion Adherence Counseling, and Introductionto AIDS Clinical Care.

In early 2004, the Botswana Ministry ofHealth broadened the KITSO AIDS Train-ing Program to include more partner or-ganizations, including ACHAP, Baylor Col-lege of Medicine, BOTUSA, the Ministry of

Health's AIDS/STD Unit, and the Univer-sity of Botswana. As the national ARV pro-gram expanded to more sites in the country,KITSO worked hand in hand with its part-ners to add more training sessions. KITSOfaculty recently reached their goal to traincore teams of healthcare professionals ateach of the 32 national ARV administrationsites. The program has instructed 2,941 par-ticipants, which include physicians, phar-macists, nurses, and pharmacy techniciansin Botswana.

The KITSO faculty, once mainly com-prised of international clinicians, now reliesconsiderably on locally-based trainers. Theyhave helped to refine the curriculum tomeet the emerging needs of the Botswanahealthcare system – making the programsustainable for the future.

The Honorable Joy Phumaphi, the for-mer Minister of Health of Botswana, hasspoken highly of the program. She said,“Knowledge, we are told, is power, andKITSO intends to equip participants withthe appropriate tools to be more effective.KITSO not only represents the primary ob-jective of sharing information and learningfrom one another, but the philosophy servesas an inspirational message to all those com-mitted to caring for our families and com-munities who have been affected by the dev-astating spread of this epidemic.”

IFocus: KITSO AIDS Training Program

New Publication AIDS in AsiaAIDS in Asia is a newly published com-prehensive AIDS reference book for pub-lic health and medical professionals.Edited by Drs. Yichen Lu and MaxEssex, this volume provides concreteinformation on the molecular epidemiol-

ogy, diagnosis, treatment, care, preven-tion and impact of AIDS. The referencealso provides an overview of the ongoingcollaborative efforts involved in severalnations in the worldwide war againstAIDS. The countries and regions re-searched include Thailand, India, China,

Japan, Hong Kong, Taiwan, Vietnam,Indonesia, Nepal, Cambodia, Myanmar,Malaysia, Pakistan, the Philippines, Laos,Sri Lanka, and Hawaii and the PacificIslands. Order your copy through theHAI website at: http://aids.harvard.edu.

News & Events

Dr. Knort Mwantembe completed AIDSClinical Care Fundamentals and PracticalIntegrated Attachment. He currently headsthe ARV clinic in Kanye.

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Dr. Irene Koulinska was born in Bulgaria,but calls Mozambique her home. She sawthe spreading plight of AIDS at home andsoon understood her mission. Dr. Koulinska,a candidate for a 2005 Doctor of Sciencedegree at the Harvard School of PublicHealth, will ultimately return to Mozam-bique to participate in and promote researchto help change the tide of the epidemic.

Spotlight: What inspired you to work inHIV/AIDS?

IK: My interest in HIV started when Iwas in medical school in Mozambique. Atthat time I was able to witness the sharprise of the epidemic in this country andthe helplessness of the medical staff in

providing treatment and care to thegrowing numbers of HIV-positive pa-tients. The situation in the pediatricswards was especially difficult. HIV diag-nosis was not possible in infants youngerthan 18 months based on the availablelaboratory tests and no counseling wasprovided to mothers.

My interest in this new and devastat-ing disease was natural under those cir-cumstances and I joined the Immunolo-gy Department at the National HealthInstitute in Mozambique, which was thelocal leader in HIV-related research.

Spotlight: What are the aims of your re-search work?

IK: My work at the Harvard School ofPublic Health and HAI is in the contextof a collaboration between our depart-ment and the department of nutrition,which focuses on mother-to-child trans-mission (MTCT) of HIV-1 in a large co-hort established in Tanzania. Initially, Ianalyzed genomes of recombinant virusesfrom HIV-1 infected infants in an at-tempt to identify genetic determinantsfor vertical transmission. Currently, myfocus is on virus-related risk factors forHIV-1 transmission by breastfeeding.

We found that some viral subtypes aretransmitted earlier than others and thatintersubtype recombinant viruses weremore likely to be transmitted to the in-fant through their mothers’ milk in com-parison to non-recombinant parentalsubtypes. Such differences are important

in deciding the best timing to initiateARV drug therapy in the mother in orderto decrease the rates of MTCT.

We are also trying to determine whetherfree virus or infected cells are more effi-ciently transmitted through the infantmucosa at different stages of lactation.Further knowledge on the mechanism ofbreast milk HIV-1 transmission would beimportant in vaccine and drug design.

Spotlight: What is the most challengingaspect of your research?

IK: Switching from clinical work andserological assays to molecular biologytechniques was a significant change forme, but fortunately my advisor, Prof.Max Essex, and other researchers in thedepartment provided great help andguidance in this process.

There have been many technical chal-lenges such as the cloning of full-lengthHIV-1 genomes and the amplification ofvirus from human milk, where its con-centration is very low. Other issues in-clude providing answers of practical im-portance in controlling the epidemic inthe developing world. Formulating hy-potheses to be answered by studies nest-ed within the existing cohort in Tanzaniaare also concerns.

The best resource for tackling these is-sues is the constant interaction with alarge team of researchers with differentbackgrounds and nationalities. All ofthese perspectives help make sure we findthe most comprehensive solutions.

VVVV iiii eeee wwww pppp oooo iiii nnnn tttt ssss An Interview with Dr. Irene Koulinska

Dr. Irene Koulinska, AIDS Researcher

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Multivitamin Supplements Delay Progression of HIV Among WomenHIV-infected pregnant women in Tanza-nia taking a daily regimen of multivita-mins significantly delayed the progress ofthe AIDS virus. The results are from a re-cent study by the Harvard School of Pub-lic Health and Muhimbili UniversityCollege of Sciences in Dar es Salaam,Tanzania. Published in the July issue ofthe New England Journal of Medicine,the study, “A Randomized Trial of Multi-vitamin Supplements and HIV DiseaseProgression and Mortality,” also suggestsa new low-cost means for health careproviders to delay the initiation of ex-pensive ARV drug therapy.

The double-blind, placebo-controlledtrial examined the effect of micronutrientsupplements on 1,078 HIV-infectedpregnant women. Researchers evaluatedthe risks of clinical disease progression,HIV-related complications, CD4+ cellcounts, and viral load. The women re-ceived a daily dose of one of four regi-mens: vitamin A alone, multivitamins ex-cluding A (with vitamins C, E, and Bcomplex), multivitamins containing vita-min A, or a placebo. All women received

standard doses of antenatal folic acid andiron. All children received the six-month-ly doses of vitamin A, which was in accor-dance with the Tanzanian standard of care.

Researchers found that participantsfollowing the regimen were less likely torapidly progress to the WHO stage 4 ordie from AIDS-related causes. Partici-pants also had higher CD4 immune cellcounts, lower viral loads and reducedcomplications of HIV infection includ-ing difficulty in swallowing, oral thrush,oral ulcers, diarrhea and fatigue.

Dr. Wafaie Fawzi, the lead author andassociate professor of nutrition and epi-

demiology at Harvard School of PublicHealth, said, “Our findings should en-courage the use of multivitamin supple-ments as supportive care to those infect-ed with HIV. As ARV therapy becomesavailable in less developed countriesmany HIV-infected persons will be iden-tified who do not meet the internationalguidelines for initiation of therapy. Ourdata suggest that multivitamins delay theonset of disease and thus extend the timeuntil such therapy is necessary.” Dr.Fawzi added, “Multivitamin supplemen-tation is inexpensive, $15 per person peryear. Introducing these supplementswould enhance compliance with moni-toring prior to clinical eligibility for ARVdrugs, preserve these drugs for later stagesof the disease, avert adverse events asso-ciated with them, and result in betterquality of life among HIV infected per-sons and significant treatment-relatedcost savings.” The study was supportedby the National Institute of Child Healthand Human Development and the Foga-rty International Center of the NationalInstitutes of Health.

Studying theCost-effectiveness of HAARTBotswana currently provides the second-largest free ARV treatment program in theworld treating over 24,000 Botswana citi-zens. In operating the successful program,however, government officials, along withresearchers at the Botswana–Harvard Schoolof Public Health AIDS Initiative Partner-ship for HIV Research and Education, real-ized that effective treatment would involvemore than distribution of low-cost ARVmedications. Given limited resources, theteam saw that efficiency (i.e. treating themaximum number of HIV-infected citizensgiven the governmental budget constraints)and sustainability were important issues.

In response to these concerns, HAI re-searchers initiated the Cost-Effectiveness ofHighly Active Antiretroviral Therapy(HAART) in Botswana study in 2003. InPhase I of the study, researchers evaluated

the government HAART program based onthe cost of treating 10,000 people over a tenyear period. Using a population disease pro-gression rate derived from published data,the estimated program cost amounted toUS$87.8 million. The preliminary datafrom Phase I indicated that the programwould almost double the average years livedfrom 4.36 years to 7.47 years. Every year oflife gained would only cost the Botswanagovernment US$1,705 per person.

Researchers are now entering Phase II ofthe study. They are collecting directly ob-served healthcare resource use data and dis-ease projection rates of HIV-1C infected in-dividuals to more correctly depict the reali-ty of HIV/AIDS and its impact on healthcare resources in Botswana.

The Study of HopeResearchers for the Tshepo study, the firstlarge-scale research study of ARV therapy in

Botswana, are quickly nearing their goal offull enrollment of 650 by December 2004.The current enrollment of the 596 studyparticipants was aided by an active commu-nity education board. The board helped in-form the public about the purpose and goalsof the study.

On October 25, the Tshepo study host-ed a visit by the board members of its fun-der, “Secure the Future,” a Bristol MyersSquib program. The program works withindividuals, institutions and governmentsto find sustainable solutions for communi-ties suffering from the HIV/AIDS epidem-ic. Board members also toured the Nation-al HIV Reference Laboratory, the central fa-cility for scientific research and training,built through a partnership with “Secure theFuture,” the Botswana government and HAI.

To learn more about these programs, visithttp://aids.harvard.edu/programs.

Research & Intervention Programs

First Economic Evaluation Round-table in Southern AfricaThe Enhancing Care Initiative-KZNPLUS, in association with HAI and theHealth Economics and HIV/AIDSResearch Division, University of Kwa-Zulu-Natal, hosted the first EconomicEvaluation Roundtable. The meeting washeld at the Nelson R. Mandela School ofMedicine, in Durban on September 22,2004. Southern African health economicexperts and public health specialistsinvolved in economic evaluations of ARVprograms, examined their role in inform-ing policy decisions. This is particularyimportant since ARV programs are beingintroduced and expanded in resource-scarce settings.

Participants reviewed the state ofhealth economics research at the begin-ning of large-scale ARV programs in the

region. They identified appropriate meth-odologies for economic evaluations ofARV programs in the context of limiteddata and resource constraints. They alsoset research priorities which included ex-panding data points to capture the costsassociated with treatment failures andswitches, and considering costs for provi-sion of equal access to healthcare. Dr.Marionette Holmes of HAI, presentedthe methodology and challenges associat-ed with economically evaluating theBotswana HAART program. Dr. Holmesstated, “As countries in sub-SaharanAfrica provide critical care and treatmentto their citizens, highly efficient alloca-tion of already strained national resourcesbecomes paramount. We are confidentour analyses will recommend the mostcost-effective strategies in ultimatelyhelping those who need it most.”

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SPOTLIGHT is published by the

Harvard School of Public Health AIDS Initiative651 Huntington AvenueBoston, MA 02115 USAPhone: 617-432-4400Fax: 617-432-4545Email: info@eci.harvard.eduWeb: aids.harvard.edu

Chair: Max EssexExecutive Director: Richard Marlink

PUBLICATIONS STAFFEditor: Yvonne NgPrint Designer: Paula TelchContributing Writers: LeAnna Alderman Sterste,Patricia Burns, Marionette Holmes, Philip Rotz

The efforts of HAI depend very much on your sup-port. Contributions to the HAI are tax deductible. To learn more, please call Michael Voligny at 617-384-8980.

Sunday, November 14, 2004OHA Africa Gala 2004 for Hope, Health, and HealingToronto Convention Centre, Toronto, Canada(Ontario Hospital Association)

November 26-28, 2004AIDS Clinical Care Fundamentals Course for Private PractionersGaborone, Botswana(KITSO AIDS Training Program)

For more information on these events visit: http://aids.harvard.edu/conferences_events

November 29-30, 2004Laboratory Fundamentals and Practical Laboratory Training CourseNational ARV site, Gweta, Botswana(KITSO AIDS Training Program)

Wednesday, December 1, 2004World AIDS Day: Challenging the Crisis in AfricaHarvard School of Public Health, Boston, MA(HAI)

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