To the Editor: As professionals working in a resource-limitedcountry to prevent the transmission of the human immunodeficiencyvirus (HIV) from mother to child and to promote child survivaland the use of highly active antiretroviral therapy (HAART),we read with interest the articles about abrupt weaning andprophylaxis regimens in infants by Kuhn et al. and Kumwendaet al. (July 10 issue).1,2 Harm-reduction alternatives for HIV-infectedmothers who breast-feed are essential. However, in the studyby Kuhn et al., the risk of mother-to-child transmission ordeath among breast-fed infants, whether they were abruptly weanedor not, was more than 30%.1 Extended antiretroviral prophylaxiswas superior to single-dose nevirapine, but 8.0% of infantswere infected at birth; postnatal mother-to-child transmissionrelated to breast-feeding added a 5.2% or 6.4% risk of infection.2Alternatives should be considered, including HAART (which isnow available to HIV-infected persons in Zambia,3 Malawi,4 andthe Dominican Republic5), formula, and improved access to potablewater. From 1999 to 2005, the rate of mother-to-child transmissionof HIV among our patients, most of whom have low levels of bothincome and education, was 3.3% with the use of multidose antiretroviraltreatment and exclusive formula-feeding; 2.8% of uninfectedinfants died. Pregnant women in developing countries can useHAART, prophylaxis regimens for infants, formula, and home-purifiedwater. The cost is significant, but the savings (in lives, orphancare, and treating infected children) are also significant.
José A. Román-Poueriet, M.D. Nicole C. Kley,M.D. Consuelo M. Beck-Sagué, M.D. Clínica de Familia Misión Internacional de Rescate La Romana, Dominican Republic rocknrollmd{at}hotmail.com
References
Kuhn L, Aldrovandi GL, Sinkala M, et al. Effects of early, abrupt weaning on HIV-free survival of children in Zambia. N Engl J Med 2008;359:130-141. [Free Full Text]
Kumwenda NI, Hoover DR, Mofenson LM, et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med 2008;359:119-129. [Free Full Text]
Stringer JS, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 2006;296:782-793. [Free Full Text]
Banda AC, Makombe SD, Jahn A, et al. Antiretroviral therapy in the Malawi defence force: access, treatment outcomes and impact on mortality. PLoS ONE 2008;3:e1445-e1445. [CrossRef]
To the Editor: The article by Kumwenda et al. provides invaluableinsight into the reduction of postnatal transmission of HIVin resource-poor settings. However, the authors did not discussone important facet of their study: the ascertainment of theinfants' HIV status at birth.
For obvious reasons, only infants who were not HIV-infectedwere included in the study. Unfortunately, in resource-poorcountries, the HIV status of a child — unless the childis symptomatic — often remains unknown until 18 monthsof age. Unlike adults, children require specialized diagnostictests for HIV; these tests are not routinely available in manydeveloping countries because of exorbitant costs.1 A 2007 studyin 77 developing countries (71% of all developing countries)showed that only 8% of infants had been tested for HIV withinthe first 2 months after birth.1
Therefore, a policy of antiretroviral prophylaxis in infants,although theoretically plausible, is likely to be impeded byprogrammatic and infrastructural barriers. This sad realityis the reason why research into challenges in developing countriesshould try to mirror the reality on the ground as much as possible.
Catherine Waweru, M.Sc. University of Washington Seattle, WA 98195 cww{at}u.washington.edu
To the Editor: In the study by Kumwenda et al., the rate ofHIV infection among the infants who received postpartum prophylaxisfor 14 weeks was lower than the rate among the control population.However, incident cases of infection still occurred throughoutthe period of prophylaxis. Logically, these infants probablyhave been infected with a virus that was resistant to nevirapine,nevirapine–zidovudine, or both. Were studies done to answerthis question?
John Mills, M.D. Monash University Melbourne, VIC 3004, Australia john.mills{at}med.monash.edu.au
To the Editor: The editorial by Gray and Saloojee1 on the transmissionof HIV through breast-feeding undervalues the importance ofthe peer-reviewed data that establish that breast-feeding byHIV-infected women can be made safer and that the overall outcomesof extended breast-feeding are similar to those of replacementfeeding after 4 months of age. These interventions,2 includingthose reported in the editorial, enable the majority of HIV-infectedwomen — who live in developing countries and for whomreplacement feeding is not a viable alternative — to exercisewider affordable and culturally appropriate choices to improvechild survival.
Breast-feeding is a sustainable choice and is crucial duringa period of multiple global crises of poverty and shortagesof water, energy, and food.3 Disastrous consequences have beenreported in some programs for the prevention of mother-to-childtransmission of HIV that endeavor to support replacement feeding.4
The authors' implied criticism of the new guidelines of theWorld Health Organization (WHO) on infant feeding for HIV-positivewomen5 is misplaced. The articles they discuss in fact emphasizethe congruence of science (i.e., rational interventions) andsocial need (i.e., an informed, appropriate choice of infantfeeding).
Hoosen M. Coovadia, M.D. Anna Coutsoudis, Ph.D. Nigel C. Rollins, M.D. University of KwaZulu-Natal Durban 4001, South Africa coovadiah{at}ukzn.ac.za
References
Gray GE, Saloojee H. Breast-feeding, antiretroviral prophylaxis, and HIV. N Engl J Med 2008;359:189-191. [Free Full Text]
Coovadia H, Kindra G. Breastfeeding, HIV transmission, and infant survival: balancing pros and cons. Curr Opin Infect Dis 2008;21:11-15. [Web of Science][Medline]
Beyond scarcity: power, poverty and the global water crisis. Human development report 2006. New York: United Nations Development Programme, 2006.
Creek T, Arvelo W, Kim A, et al. Role of infant feeding and HIV in a severe outbreak of diarrhea and malnutrition among young children, Botswana, 2006. In: Program and abstracts of the 14th Conference of Retroviruses and Opportunistic Infections, Los Angeles, February 25–28, 2007. (Accessed October 3, 2008, at http://www.retroconference.org/2007/Abstracts/29305.htm.)
Dr. Taha and colleagues reply: Román-Poueriet and colleaguesprovide an example of how combined efforts to provide a safewater supply, formula, and maternal HAART can lead to substantialgains in child survival. The authors do not provide detailson who is receiving HAART — women with low CD4 cell countsor healthy women who will not qualify for HAART? We would liketo see these successful findings published in order to benefitthe scientific community and guide policy in the resource-constrainedsettings in sub-Saharan Africa.
Waweru raises an important point regarding the challenges ofearly identification of HIV-infected infants, arguing that becauseearly diagnosis in infants by means of DNA polymerase chainreaction (PCR), which was used in our study, is not widely available,extended prophylaxis in infants may not be a feasible approach.We acknowledge the cost and laboratory limitations associatedwith implementation of this approach. However, in countriessuch as Malawi, where 40 to 50% of women present late in delivery,such options for postnatal prevention of HIV transmission arenecessary. Other methods of collecting whole blood, such asdried blood spots on filter-paper cards, have also been successfullyused for HIV testing.1,2
Early diagnosis in infants remains an essential part of programsto prevent mother-to-child transmission of HIV. Preliminarydata from the Children with HIV Early Antiretroviral Therapy(CHER) Study in South Africa suggest that early identificationof HIV infection and the initiation of antiretroviral treatmentin the first 12 weeks of life can reduce mortality among HIV-infectedinfants by 75% in resource-poor settings.3 Although early diagnosisin infants remains a challenge for many countries, we are encouragedby the improved access-to-care services in several African countriesthrough the support of the President's Emergency Plan for AIDSRelief (PEPFAR) and the Global Fund to Fight AIDS. For example,in Malawi, a program involves the early diagnosis of HIV ininfants based on DNA PCR samples collected on filter-paper cards.In the first 8 months of operation, 1780 samples obtained frominfants younger than 18 months of age have been tested, withan average turnaround time of 10 days.4 Technological limitationsshould not impede our efforts to search for new and more effectivemeasures to prevent HIV infection in children.
Mills comments on incident infections in infants during theprophylaxis period and suggests that these infections couldbe due to viruses that are resistant to nevirapine or nevirapine–zidovudine.We agree that the study of resistance is critically important.We are currently performing these resistance assays, and wewill report the results when the testing has been completed.
Taha E. Taha, M.D., Ph.D. Newton Kumwenda, Ph.D. Johns Hopkins University Baltimore, MD 21205 ttaha{at}jhsph.edu
George Kafulafula, M.B., B.S. University of Malawi Blantyre, Malawi
References
Taha TE, Kumwenda NI, Hoover DR, et al. Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting: a randomized controlled trial. JAMA 2004;292:202-209. [Free Full Text]
Taha TE, Kumwenda NI, Gibbons A, et al. Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial. Lancet 2003;362:1171-1177. [CrossRef][Web of Science][Medline]
Violari A, Cotton M, Gibb D, et al. Antiretroviral therapy initiated before 12 weeks of age reduces mortality in young HIV-infected infants: evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study. Presented at the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Sydney, July 22–25, 2007. abstract. (Accessed October 3, 2008, at http://www.ias2007.org/pag/Abstracts.aspx?SID=150&AID=5557.)
Demby A, Nyirenda T, Chirwa A, et al. Critical steps for establishing laboratory capacity for early infant diagnosis of HIV infection. Presented at the 2008 HIV/AIDS Implementers' Meeting, Kampala, Uganda, June 3–7, 2008:141. oral abstract. (Accessed October 3, 2008, at http://www.hivimplementers.org/pdf/OGAC_08_BookHR.pdf.)
Dr. Kuhn and colleagues reply: We completely agree with therecommendation that HAART be given to pregnant women who meetcertain criteria. Antiretroviral therapy can save mothers' livesand effectively reduce transmission. The latter benefit diminishesfurther the justification for avoiding or shortening the periodof lactation — another benefit. Concerns regarding theuse of formula in low-resource settings are not only about costbut also, to a greater extent, about safety.1 In our trial,there was no benefit of weaning at 4 months as compared withcontinuing breast-feeding into the second year. Likewise, ina randomized trial in Botswana, HIV-free survival was not improvedwith the use of formula from birth.2 The provision of cleanwater does not eliminate the necessity of breast-feeding. Evenin wealthy communities, breast-feeding provides protection againstsevere infant morbidity.3 Prematurely truncating the normalduration of breast-feeding, like eliminating any breast-feeding,is neither safe nor effective; it is harmful in some subgroups,including HIV-infected children, and it was not widely acceptablein our study population. Harm-reduction policies that affectsuch large numbers of vulnerable infants should be evidence-basedand include only interventions that are shown to be effective.
Louise Kuhn, Ph.D. Columbia University New York, NY 10032 lk24{at}columbia.edu
Moses Sinkala, M.D., M.P.H. Lusaka District Health ManagementTeam Lusaka, Zambia
Grace Aldrovandi, M.D. Children's Hospital Los Angeles Los Angeles, CA 90027
References
Coutsoudis A, Coovadia HM, Wilfert CM. HIV, infant feeding and more perils for poor people: new WHO guidelines encourage review of formula milk policies. Bull World Health Organ 2008;86:210-214. [Web of Science][Medline]
Thior I, Lockman S, Smeaton LM, et al. Breastfeeding plus infant zidovudine prophylaxis for 6 months vs formula feeding plus infant zidovudine for 1 month to reduce mother-to-child HIV transmission in Botswana: a randomized trial: the Mashi Study. JAMA 2006;296:794-805. [Free Full Text]
Quigley MA, Kelly YJ, Sacker A. Breastfeeding and hospitalization for diarrheal and respiratory infection in the United Kingdom Millennium Cohort Study. Pediatrics 2007;119:e837-e842. [Free Full Text]
The editorialists reply: The suggestion that our editorial undervaluesthe importance of the two corresponding articles is withoutbasis. We readily acknowledged the contributions of the findingsof these studies, including their ability to extend optionsfor breast-feeding mothers. The study by Kumwenda et al. ismost pertinent for mothers who are willing to curtail breast-feedingearly, but any gains achieved are eroded by continued breast-feeding.Decisions regarding HIV and breast-feeding are highly context-specific,and generalizing evidence from a particular setting to a region,continent, or all "developing countries" must be done cautiously.
We have no qualms about the 2006 WHO consensus statement,1 butthis statement, similar to other evidence-based guidelines,must be interpreted in light of emerging evidence. There isnothing spurious about respecting women's right of choice andresponding to any perceived misguided decisions by designingand investigating appropriate scientific solutions.
The quest to provide HIV-exposed infants with breast milk thatis safe is ongoing, and the solution to eradicating or minimizingthe transmission of HIV through breast milk is tragically notyet apparent. The only guarantee to HIV-free child survivalis preventing HIV infection.
Glenda E. Gray, M.B., B.Ch. Haroon Saloojee, M.B., B.Ch. University of Witwatersrand Johannesburg 2000, South Africa
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