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Asking the right questions: developing evidence-based strategies for treating HIV in women and children Abdool Karim, Quarraisha; Banegura, Anchilla; Cahn, Pedro; Christie, Celia D; Dintruff, Robert; Distel, Manuel; Hankins, Catherine; Hellmann, Nicholas; Katabira, Elly; Lehrman, Sandra; Montaner, Julio; Purdon, Scott; Rooney, James F; Wood, Robin; Heidari, Shirin May 25, 2011

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COMMENTARY Open AccessAsking the right questions: developing evidence-based strategies for treating HIV in women andchildrenQuarraisha Abdool Karim1,2†, Anchilla Banegura3†, Pedro Cahn4†, Celia DC Christie5†, Robert Dintruff6†,Manuel Distel7†, Catherine Hankins8†, Nicholas Hellmann9†, Elly Katabira10†, Sandra Lehrman11†, Julio Montaner12†,Scott Purdon13†, James F Rooney14†, Robin Wood15† and Shirin Heidari16*AbstractIn July 2010, the World Health Organization (WHO) issued formal revisions of its guidelines on the use of highlyactive antiretroviral therapy for HIV. The new guidelines greatly expand eligibility for treatment of adults andchildren, as well as for pregnant women seeking prophylaxis for vertical HIV transmission. WHO’s newrecommendations bring the guidelines closer to practices in developed countries, and its shift to earlier treatmentalone will increase the number of treatment-eligible people by 50% or more.Scaling up access to HIV treatment is revealing important gaps in our understanding of how best to provide for allthose in need. This knowledge gap is especially significant in developing countries, where women and childrencomprise a majority of those living with HIV infection. Given the magnitude and significance of these populations,the International AIDS Society, through its Industry Liaison Forum, prioritized HIV treatment and prophylaxis ofwomen and children. In March 2010, the International AIDS Society and 15 partners launched a ConsensusStatement outlining priority areas in which a relative lack of knowledge impedes delivery of optimal prevention ofmother to child transmission (PMTCT) and treatment to women and children.The Consensus Statement, “Asking the Right Questions: Advancing an HIV Research Agenda for Women andChildren”, makes a special appeal for a more gender-sensitive approach to HIV research at all stages, fromconception to design and implementation. It particularly emphasizes research to enhance the understanding ofsex-based differences and paediatric needs in treatment uptake and response. In addition to clinical issues, thestatement focuses on programmatic research that facilitates access and adherence to antiretroviral regimens. Bettercoordination of HIV management with sexual and reproductive healthcare delivery is one such approach.We discuss here our knowledge gaps concerning effective, safe PMTCT and treatment for women and children inlight of the expansion envisioned by WHO’s revised guidelines. The guideline’s new goals present an opportunityfor advancing the women and children’s agenda outlined in the Consensus Statement.CommentaryIn July 2010, the World Health Organization (WHO)issued formal revisions of its guidelines on the use ofhighly active antiretroviral therapy for HIV. The guide-lines greatly expand eligibility for treatment of adults [1]and children [2]. They also broaden the armamentariumfor prevention of mother to child transmission(PMTCT) of HIV [3]. WHO’s recommendations, whichapply mainly to resource-restricted settings, bring theguidelines closer to the practices in developed countries[4]. At the same time, they will increase the number oftreatment-eligible patients by 50% or more [5].Changes in HIV treatment access are of special con-cern to women and children. Women notably constitute60% of the people living with HIV in the high-burdencountries of sub-Saharan Africa [6]. Furthermore, expec-tant HIV-infected mothers face the combined hazard ofvirus- and pregnancy-related health issues; they have* Correspondence: shirin.heidari@iasociety.org† Contributed equally16Research Promotion, International AIDS Society, Geneva, SwitzerlandFull list of author information is available at the end of the articleKarim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388© 2011 Karim et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.maternal mortality rates that are as much as 10-foldhigher than their HIV-uninfected peers [7]. This excessmortality might seem self-evident, yet research has yetto break down the various contributing factors, includ-ing AIDS or other comorbidities and obstetric condi-tions aggravated by immune deficiency. Children in theleast developed countries, meanwhile, suffer from thematernal HIV epidemic, as well as the paediatric one,leading to enhancement of a third concurrent epidemic,malnutrition.Considering the need to optimize the benefits of anti-retroviral treatment for women and children, the Inter-national AIDS Society’s Industry Liaison Forum (IAS-ILF) launched a mapping exercise to examine the needfor further clinical and operations research related toHIV treatment and PMTCT [8]. The mapping exerciseresulted in the Consensus Statement, “Asking the RightQuestions: Advancing an HIV Research Agenda forWomen and Children”, which was released on 8 March2010 by the IAS and 15 partners, including UnitedNations agencies, community groups, the private sectorand foundations [9]. The statement develops a usefulroadmap for developing the means to expand optimumHIV care for women and children in the manner envi-sioned by WHO’s 2010 HIV guidelines. We discuss herein detail the missing pieces in our knowledge of optimalHIV treatment in women and children and advocateadvancing this research agenda.Overcoming the hurdles to treating HIV in womenThe WHO guidelines advance the CD4 count thresholdfor initiating treatment in patients older than five yearsto 350 cells/mm3 from the previous limit of 200 cells/mm3 [1]. All patients with clinically advanced HIV(WHO stages 3 and 4) are also eligible.These criteria hold for women, as well as for men. Yetan old but unresolved debate is whether there are biolo-gical differences between men and women that influencedisease progression and treatment outcome. Two stu-dies, each enrolling more than 2000 participants, havereported that women on antiretroviral (ARV) drugs havehigher CD4 counts and slower disease progression thanmen [10,11]. Other studies have not observed any differ-ences [12,13]. Resolution of this issue is made difficultby short follow up and many confounding factors, suchas concurrent health problems, care access, ethnic originand socioeconomic factors.Another area of uncertainty over sex differences con-cerns pharmacokinetics and toxicities. These issues arisefor nevirapine and efavirenz, the two drugs that providethe high potency of WHO’s preferred first-line combina-tion regimens. There are long-established sex differencesin nevirapine’s adverse effects: women with higher CD4counts are more at risk than men at the same CD4count for hypersensitivity reactions and hepatic failureafter starting the drug [14,15]. Recent studies have con-tested this CD4 association, however [16,17]. An analysisof efavirenz found equal virologic and immunologicimprovements in men and women, but more frequenttoxicity-related drug discontinuations in women [18]. Intreatment outcome studies, factors such as race, lowerbody weight or liver function differences may confoundthe results.A third major area in which sex can complicate treat-ment decisions is hormonal contraceptives. Althoughthere is as yet no evidence that hormonal contraceptioninterferes with ARVs, there is evidence that the reverseis true. Women receiving nevirapine- or ritonavir-con-taining regimens (which are favoured by WHO for sec-ond-line therapy) will more rapidly metabolize ethinyloestradiol and norethindrone taken for contraceptivepurposes. Progesterone-based contraceptives may still befeasible, however [19].There are also controversies over the effect of hormo-nal contraception on HIV progression. Some publisheddata suggest that hormonal contraception increases therisk of HIV acquisition [20] or disease progression [21],whereas other studies contradict these results [22,23].There is an urgent need to conclusively resolve thisquestion.In addition, there has been little investigation of theinteraction between ARVs and the female hormonechanges that women experience in the course of theirlives. A number of studies have found that pregnancyreduces antiretroviral drug levels [24]. There are alsoindications that some women on ARVs undergo earlieronset of menopause [25].In contrast, the relationship between ARVs and pub-erty is uncharted territory. It is possible, for example,that ARVs contribute to delaying puberty even thoughthey reverse the endocrine-disrupting effects of chronicHIV [26]. Once teenagers do achieve puberty, optimalHIV treatment may be difficult to achieve because pub-escent adolescents have unexpectedly low drug levelsdespite reasonable adherence [27] and are at increasedrisk of ARV-associated metabolic dysfunction [28]. Withthe growing availability of paediatric antiretroviral treat-ment, an increasing number of children are survivinginto and through adolescence. The long overlookedresearch on this age group’s response to ARVs hasbecome a pressing issue.Women are in a more vulnerable position than menin many parts of the world, and often their lesser socio-economic status and decision-making power constrainstheir ability to seek out care on their own [29-31].Nonetheless, a greater proportion of women than menwith HIV are diagnosed and receive ARVs. Due to theirbiologic, social and family roles, women more readilyKarim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 2 of 9seek contact with the healthcare system, where they canreceive HIV testing [32-34] and care [34-36].Women would benefit, therefore, from an integrationof HIV programmes with broader sexual and reproduc-tive health services [37,38]. This possibility signals theneed to intensify oft-ignored operations research intowomen’s care delivery. Such research, which includesprogramme evaluations, can show how to optimize anti-retroviral therapy by improving HIV diagnosis and long-term follow up of women at different socioeconomiclevels. The need is particularly critical for marginalizedsubpopulations of adolescent and adult women. Womenliving in remote areas, single women, widows, sex work-ers, women who use drugs, transgender individuals andwomen who are indigent or from racial minoritiesshould receive special attention.Extending prophylaxis for prevention of verticaltransmissionIn 2008, an estimated 45% of pregnant women inresource-limited countries received PMTCT regimens,but these were generally simpler and shorter than theregimens that WHO now advocates [39].The 2010 PMTCT guidelines primarily advise provi-sion of potent triple antiretroviral therapy for preventionof vertical transmission in pregnant women [3]. Thus,pregnant women who present at prenatal clinics withserious HIV-related symptoms or CD4 counts below350 cells/mm3 will receive a highly suppressive antire-troviral regimen, as recommended for all adults for theirown health. The triple regimen will also minimize therisk of transmission of HIV to the foetus and breastfeed-ing infant.The new WHO guidelines propose that expectantHIV-positive mothers with CD4 counts above 350 cells/mm3 receive triple-drug regimens, too, starting at 14weeks of gestation and continuing through weaning [3].Evidence shows that suppressive combination therapyfrom late pregnancy through six months of breastfeed-ing can reduce mother to child HIV transmission tobelow 1% [40].The guidelines, in addition, offer a cheaper option forwomen with CD4 counts above the 350 cells/mm3threshold: of zidovudine monotherapy from 14 weeks ofgestation until birth. Mothers may also receive single-dose nevirapine during labour, plus a week of zidovu-dine/lamivudine combination post-partum. Breastfeedinginfants in this case receive nevirapine prophylaxis untilweaned. Non-breastfeeding infants receive nevirapine orzidovudine for six weeks after birth.Studies that examine and compare the efficacy ofWHO’s two PMTCT options, triple regimen versus sim-plified regimen, would be very valuable. An 805-birthstudy in three African countries found no significantdifference in pre-birth transmission rates when compar-ing three-drug regimens to what is now the simplerWHO alternative (though starting only after week 26)[41]. As for transmission during breastfeeding, a trialfollowing 2369 Malawi births reported no significant dif-ference between maternal triple therapy and infant dailynevirapine [42].Another outstanding question is the impact of inter-mittent therapy on women’s future treatment options.There is growing evidence that administering single-dose nevirapine during labour - the most commonPMTCT regimen used in low-income countries -increases the risk of developing nevirapine-resistant HIV[43]. The revised guidelines recommend seven days ofzidovudine/lamivudine post-partum to overcome thisproblem by inhibiting HIV replication while the nevira-pine is slowly being cleared from the mother’s body.Additional studies are needed to address resistance con-cerns of the guideline revisions, in particular, conse-quences of zidovudine monotherapy from 14 weeks ofgestation and continued during pregnancy [44].Furthermore, the Strategies for Management of Anti-retroviral Therapy (SMART) trial found that episodicHIV-suppressive ARV combinations result in greatermortality and morbidity than continuous therapy[45,46]. Initial research has not confirmed this increasein women who terminate ARVs after delivery, but defi-nitive data for women with CD4 counts of more than350 cells/mm3 are not yet available [47].WHO’s PMTCT revisions raise a number of opera-tional issues concerning the ability of treatment pro-grammes to accommodate the new recommendations.Initial studies indicate that instituting the new recom-mendations would triple the number of HIV infectionsaverted [48,49]. Having effective regimens is not enoughall by itself, however; effective delivery programmes areeven more important [50].There remain many research questions involvingdelivery of extended PMTCT [9]. Central to this effortis, once again, integration of services [51,52]: healthcaresystems need to investigate the feasibility of providingantiretrovirals to pregnant women as part of routinematernal care in antenatal clinics. Task shifting and tasksharing, which allow lower-level healthcare staff toassume greater responsibilities, could be of great assis-tance here [53]. Retention strategies are critical, too.Investigating the best means for maintaining contactwith HIV-positive mothers and their infants is vital forPMTCT success. Family-centered care, which meets thecontinuing health needs of the entire household, may bea key strategy here [54]. Local programmes will have tolearn how to adapt to their clients’ cultural background,providing services that make them feel respected andsafe.Karim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 3 of 9Uninfected infants exposed to antiretroviral drugsUnder the 2010 WHO guidelines, infants could have upto more than two years of in utero and post-partumantiretroviral drug exposure [3]. The immediate prophy-lactic benefits of this extended exposure are well recog-nized and outweigh any potential risks. There is,however, little knowledge of any adverse consequencesfor the resulting large numbers of HIV- and ARV-exposed but uninfected children, which is essential foroptimal monitoring and management of any potentialhazards.Birth defects are an initial concern regarding first-tri-mester exposure to efavirenz. Studies conflict on thissubject [55-57], and the WHO guidelines strongly advisenon-pregnant women on efavirenz to use a secure formof birth control [3].A number of studies have also reported conflictingfindings regarding low birth weight and preterm deliv-eries following exposure to ARVs [58-61]. A 2007 meta-analysis found a large amount of variation in the differ-ent studies’ methods and findings [62]. Overall, a greaterrisk of preterm delivery was associated with starting tri-ple-drug therapy before pregnancy or in the first trime-ster and with the use of protease inhibitors at any pointduring pregnancy. An 8192-infant French study asso-ciated lower birth weights to triple-drug regimens com-pared with monotherapy, but inferred that thedifference was due to confounding factors [61]. Chiefamong these was that pregnant women with advancedHIV in 1997-2004 were more likely than others toreceive triple therapy. Resolving this nettlesome issue isessential for choosing PMTCT regimens and planninginfant healthcare in areas of high HIV prevalence.A further area of disagreement concerns mitochon-drial toxicity in ARV-exposed, uninfected infants.Mitochondrial toxicity would lead to such conditionsas lactic acidosis, pancreatitis, cardiomyopathy andneuropathy. Some cohort studies have observed signsof mitochondrial impairment in ARV-exposed infants[63,64]. Researchers have argued, too, that in uteroHIV exposure itself leads to mitochondrial damage[64,65]. Yet another issue is haematologic toxicities: alongitudinal study of more than 4000 children aged 0to 18 months found that haemoglobin levels, whiteblood cells and platelets were transiently reduced inARV-exposed children [66]. Investigation is also conti-nuing regarding effects of in utero ARVs on cardiacfunction and cardiomyopathy in HIV-exposed butuninfected infants [67].Other ARV exposure concerns are an increased risk ofinfectious diseases in the newborn and potential formalignancies later in life [68,69]. There has been noconfirmed elevation in malignancies, but cancers cantake years to develop [70]. Longitudinal studies,including cohorts that follow up infants and childreninto adulthood, are required to answer this question.As with malignancies, documentation of changes ingrowth and development has proved elusive. Here, too,studies have been carried out until only a few years ofage [71,72]. More extensive and longer follow up iscalled for to detect subtle or lingering toxicities. Alongthose lines, the Paediatric HIV/AIDS Cohort Study inthe United States has instituted a Surveillance Monitor-ing of Antiretroviral Toxicity project to prospectivelyfollow more than 2000 ARV-exposed, uninfected infantsto evaluate late toxicities [73].The incidence of subtle adverse events is likely to riseas the length of ARV exposure grows as the revisedWHO guidelines are implemented [3]. Studies of unin-fected children will have to tease out the separate con-tributions of exposure to ARVs and maternal HIV andenvironmental and economic factors. Understandingthese will be necessary to help identify the best strate-gies that minimize both the risk of HIV transmissionand any compromise of growth and development. Amore comprehensive pharmacovigilance system, forexample, by expanding the existing network of antiretro-viral pregnancy registries to include low- and middle-income paediatric cohorts, should explore models forlonger-term monitoring of uninfected children exposedin pregnancy and during extended postpartumprophylaxis.New treatment options for children with HIVThe paediatric HIV incidence in high-income countrieshas shrunk to a very low level due to the success ofPMTCT using suppressive triple-drug regimens. Inresource-limited areas, where PMTCT coverage is sub-optimal, an estimated 370,000 infants are born annuallywith HIV infection [74]. As with adults, WHO’s 2010paediatric guidelines will greatly broaden the goals fortreating these children [2].Studies have clearly demonstrated the survival benefitsof providing immediate therapy to HIV-infected infants[75-77]. A groundbreaking South African study reportedthat deferring antiretroviral therapy until CD4 levelsbecome low or symptoms appear increases infant mor-tality by more than 400% [78]. WHO, in response,recommended that all HIV-infected children under oneyear of age receive ARVs [76]. It is now raising thatrecommendation to the age of two years [9]. Recom-mendations for children older than two years includeCD4 count and clinical criteria in line with those in thenew adult guidelines.Provision of immediate treatment to infants requiresthat they be identified in timely fashion. Postnatal followup is notoriously weak in resource-constrained settings,and especially so for undiagnosed infants with HIVKarim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 4 of 9exposure [79]. Due to the persistence of maternal anti-bodies, infants younger than 18 months require sophisti-cated, expensive virologic testing for a definitive HIVdiagnosis. Only 15% of infants born to HIV-positivemothers received such testing during the first twomonths of life in 54 countries reporting this informationin 2009 [39]. The WHO guidelines include recommen-dations for symptom-based, presumptive diagnosis ofsevere HIV disease in areas where virologic testing isunavailable.Strengthening infant services is critical to ensureprompt diagnosis and retention in HIV care. Integrationof HIV care with other health services, along with taskshifting and sharing, again promises to help ensuremore consistent HIV management. Inclusion of commu-nity social networks and other household members(fathers, in particular) will provide substantial supportfor these efforts.An issue particular to children older than age twoyears is the effect of ARVs on growth and development.If the drugs retard development, it would not be advisa-ble to start ARVs earlier than necessary. The influenceof HIV infection, however, confounds that of ARVs.Recent reports indicate that children who start treat-ment with less advanced HIV disease and less growthdeficiency tend to gradually normalize their height andweight [80-82]. Children who initiate treatment later inthe HIV disease process also gain weight and height, butat a slower rate. Even so, children remain on a growthtrajectory determined by nutritional and environmentalconditions. Analogous problems exist when studyingother aspects of development, such as neurocognitivematuration and bone growth.Starting ARVs also depends on the relationshipbetween antiretroviral drugs and concurrent conditions.More research is required in this area, too. A particu-larly critical area is tuberculosis (TB) treatment in chil-dren. Mutual liver toxicities and drug-drug interactionscreate complicated treatment management problems forchildren infected with both HIV and TB. A study inSouth African children aged seven months to 3.9 yearsshowed that it is possible to attenuate the tendency oflopinavir levels to decline in the presence of the TBdrug, rifampicin, by using a higher dose of concomitantritonavir (lopinavir/ritonavir ratio of 1:1 instead of theusual 4:1) [83]. The drawback is that children then haveappreciable elevations in serum liver enzymes [84].Paediatric treatment problems would be easier toresolve if there were as many available antiretroviraloptions as there are for adults. Unfortunately, many bar-riers retard development of paediatric ARV formulationsfor resource-restricted settings. Optimal and acceptableoptions for infants and children are of growing necessitybecause of concern about resistance due to single-dosenevirapine exposure during PMTCT, and also concernabout emergence of resistance during treatment in chil-dren [85,86].There is now low demand for paediatric ARVs inhigh-income countries, and so little financial incentiveto bring new formulations to the market. In low- andmiddle-income countries, the available liquid paediatricformulations present a number of practical difficulties:bulk transport and storage is difficult because liquid for-mulations tend to have short shelf lives or requirerefrigeration. Also, their lack of palatability and largevolume create household obstacles to adherence. TheWHO guidelines stress that fixed-dose formulationscombining multiple drugs in a single pill would be animportant step to simplifying regimens [2]. Achievingadvances of this order require multisectoral partnershipsinvolving industry, private donors and internationalagencies [87].Moving forwardThe Consensus Statement, “Asking the Right Questions:Advancing an HIV Research Agenda for Women andChildren”, issued by the IAS and its partners, identifiesthe research needed to bring advanced HIV treatmentto women and children in resource-limited countries[9]. The statement’s overarching recommendations callfor more extensive HIV research on women and chil-dren, for widely sharing data, and for better dissemina-tion of results. It makes a special appeal for consistentlydesigning HIV research to include a provision for gen-der analysis. This analysis should especially stress signifi-cant parameters, such as retention in ARV programmes,sexual and reproductive health, morbidity and mortality,and loss to follow up (Additional file 1: Box 1).The Consensus Statement includes several other majorunmet research needs relevant to providing women withequitable, quality care. Scientific progress requires, firstof all, designing observational cohorts and clinical trialsto permit stratification by sex, race and ethnicity to pro-vide the missing data needed to determine sex-baseddifferences in pharmacokinetics and pharmacodynamics,treatment outcomes and adverse events (Additional file1: Box 2). Well-designed, prospective impact evaluationstudies could play an instrumental role in identifyingnew solutions as programmes are brought up to scale.For children, the prime unmet need is a comprehen-sive system for tracking the continuing effects of HIVdrugs. Expanding existing antiretroviral pregnancy regis-tries to include low- and middle-income paediatriccohorts is an initial step. These cohorts should exploremodels for longer-term monitoring of uninfected chil-dren exposed in utero and during extended postpartumprophylaxis. The Consensus Statement further advocatesadvancing infant services to ensure prompt diagnosisKarim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 5 of 9and retention in HIV care. It also calls for a renewedresearch investment to develop improved paediatricARV formulations, as well as advanced modalities fortreating HIV and comorbid conditions in children(Additional file 1: Box 3).Women and children alike would benefit from inte-gration of HIV programmes with broader health servicesand a more family-centred approach. This possibilitysignals the need to intensify oft-ignored operationsresearch on care delivery to identify strategies to opti-mize HIV treatment and PMTCT programmes for var-ious populations. Special attention needs to be paid tolinking women and children to a continuum of care -from HIV testing of pregnant women all the waythrough provision of PMTCT, early infant testing, andlinkage to paediatric treatment and care as needed. Theneed is particularly critical for marginalized adolescentsand adult women, women living in remote areas, singlewomen, sex workers, women who use drugs, transgen-der individuals, indigenous women, and women fromethnic minorities.Retention strategies are critical here. Investigating thebest means for maintaining contact with infectedmothers and their offspring is vital for successful HIVmanagement. Local programmes will have to learn howto adapt to their clients’ cultural backgrounds, providingservices that make them feel respected and safe. Inclu-sion of community social networks and other householdmembers, including men, may provide substantial sup-port for these efforts.As we summarize here, HIV research has a long wayto go in addressing women and children’s specificneeds. Yet understanding their issues is central to con-trolling HIV, as well as other diseases. The researchagenda laid out by the statement is designed to result innew strategic thinking for women and children, andsupports a collaborative effort among key players,including those from industry.Additional materialAdditional file 1: Boxes. Box 1: Overarching recommendations toimprove research for women and children. Box 2: Recommendations forclinical and operations research for treatment for women and girls. Box3: Clinical and operations research recommendations for PMTCT andpaediatric care, treatment and support.AcknowledgementsThe authors are thankful to all signatories of the Consensus Statement,“Asking the Right Question: Advancing an HIV Research Agenda for Womenand Children”. These are: AVAC, Global Advocacy for HIV Prevention;Boehringer Ingelheim; Clinton Health Access Initiative (CHAI); Coalition onChildren Affected by AIDS (CCABA); Elizabeth Glaser Pediatric AIDSFoundation (EGPAF); European AIDS Treatment Group (EATG); InternationalCommunity of Women Living with HIV/AIDS (ICW); International TreatmentPreparedness Coalition (ITPC); Merck; Treatment Action Group (TAG);UNAIDS; UNICEF; ViiV Healthcare; and WHO. We are also grateful to allstakeholders that contributed to the consultation process resulting in thejoint Consensus Statement.The mapping exercise and the consultation process that resulted in theEnvironmental Scan, “Mapping HIV Research Priorities for Women andChildren”, and the Consensus Statement is an initiative of the IAS IndustryLiaison Forum. It was financially supported by unrestricted educationalgrants from Abbott, Boehringer Ingelheim, Gilead, Merck, Pfizer and Tibotec,as well as the International AIDS Society. The mapping exercise was guidedby an Expert Reference Group, including experts from UN agencies andpublic institutions. The authors are grateful for their guidance and support.The authors would like to acknowledge the contribution of David Gilden,Rodney Kort and Clemens Roll, independent consultants who providedsupport in search and review of literature of the environmental scan. DavidGilden also provided support in drafting and revising this manuscript.Author details1Department of Epidemiology, Columbia University, New York, USA.2Prevention and Epidemiology, Centre for the AIDS Programme of Researchin South Africa, Durban, South Africa. 3Global Virology Access, TibotecPharmaceuticals Ltd, Nairobi, Kenya. 4Direccion Cientifica, FundacionHuesped, Buenos Aires, Argentina. 5Department of Pediatrics, University ofthe West Indies, Kingston, Jamaica. 6Commercial Development, Abbott,Abbott Park, Illinois, USA. 7Medical Affairs, Boehringer Ingelheim GmbH,Ingelheim, Germany. 8Office of the Deputy Executive Director, UNAIDS,Geneva, Switzerland. 9Medical and Scientific Affairs, Elizabeth Glaser PediatricAIDS Foundation, Washington, DC, USA. 10Department of Research, MakerereMedical School, Kampala, Uganda. 11Scientific Affairs - Infectious Diseases,Office of the Chief Medical Officer, Merck & Co, Upper Gwynedd,Pennsylvania, USA. 12AIDS Research and Head of Division of AIDS, Universityof British Columbia, Vancouver, Canada. 13Access and Government Affairs,ViiV Healthcare, Middlesex, UK. 14Medical Affairs, Gilead Sciences, Foster City,California, USA. 15Institute of Infectious Disease and Molecular Medicine,Desmond Tutu HIV Centre, University of Cape Town, South Africa. 16ResearchPromotion, International AIDS Society, Geneva, Switzerland.Authors’ contributionsSH, with the support of independent consultant David Gilden, wrote the firstdraft. All authors contributed equally to the manuscript by providingcomments on subsequent drafts. All authors have read and approved thefinal version.Competing interestsQAK, CC, CH, EK have no competing interests.AB is an employee of Tibotec Pharmaceuticals Ltd. PC has served as:advisory board member in Avexa, Gilead, GSK, Myriad, Merck, Pfizer,Pharmasset, Schering Plough and Tibotec; Investigator in Avexa, BoehringerIngelheim, Gilead, GSK, Roche, Merck, Pfizer, Pharmasset, Schering Plough,Tibotec, Abbott and BMS; Speaker (content and design performed by thespeaker, no company control) for Abbott, BMS, Boehringer Ingelheim, GSK,Merck, Pfizer and Tibotec; and Scientific Advisor for Merck Sharp & Dohme,Pfizer, GSK, Avexa and Tibotec. He is not a shareholder in anypharmaceutical company; nor has he any commercial interest or investmentin any pharmaceutical company. MD is an employee of BoehringerIngelheim GmbH. RD is an employee of Abbott. NH is an employee of theElizabeth Glaser Pediatric AIDS Foundation. SL is an employee of Merck. JMhas received grants from, served as an ad hoc advisor to, or spoken atvarious events sponsored by, Abbott, Argos Therapeutics, Bioject Inc,Boehringer Ingelheim, BMS, Gilead Sciences, GlaxoSmithKline, Hoffmann-LaRoche, Janssen-Ortho, Merck Frosst, Panacos, Pfizer, Schering, Serono Inc,Thera Technologies, Tibotec (J&J) and Trimeris. He is also supported: by theMinistry of Health Services and the Ministry of Healthy Living and Sport inthe Province of British Columbia; through a Knowledge Translation Awardfrom the Canadian Institutes of Health Research (CIHR); and through anAvant-Garde Award (No. 1DP1DA026182-01) from the National Institutes ofDrug Abuse, at the US National Institutes of Health. He also receivedfunding from Merck, Gilead and ViiV to support research into Treatment asPrevention. SP is an employee of ViiV Healthcare. JR is an employee andstockholder in Gilead Sciences. RW has affiliations as scientific advisor withBoehringer-Ingelheim, Gilead, GlaxoSmithKline, Merck, Pfizer, Tibotec,Karim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 6 of 9CareWorks, Togalabs, INSIGHT (NIH) and the International Partnership forMicrobicides. SH is an employee of the International AIDS Society, and hersalary is provided partly by unrestricted educational grants from thefollowing pharmaceutical companies: Abbott, Boehringer Ingelheim, Gilead,Merck, Pfizer, Tibotec and ViiV Healthcare. For these authors, there are noconflicts of interest in co-authoring this article.The conclusions and opinions expressed in this article are those of theauthors and do not necessarily reflect those of their respective organizations.Received: 6 October 2010 Accepted: 25 May 2011Published: 25 May 2011References1. World Health Organization: Antiretroviral therapy for HIV infection in adultsand adolescents: recommendations for a public health approach 2010 [http://whqlibdoc.who.int/publications/2010/9789241599764_eng.pdf], Accessed 4August 2010.2. World Health Organization: Antiretroviral therapy for HIV infection in infantsand children: towards universal access 2010 [http://whqlibdoc.who.int/publications/2010/9789241599801_eng.pdf], Accessed 4 August 2010.3. World Health Organization: Antiretroviral drugs for treating pregnant womenand preventing HIV infection in infants: recommendations for a public healthapproach 2010 [http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf], Accessed 4 August 2010.4. Severe P, Pape J, Fitzgerald D: The Haiti Cipra Team: A randomizedclinical trial of early versus standard antiretroviral therapy for HIV-infected patients with a CD4 T cell count of 200-350 cells/ml(CIPRAHT001) [abstract]. Program and Abstracts of the 49th InterscienceConference on Antimicrobial Agents and Chemotherapy: 12-15 September2009 San Francisco;Abstract H-1230c.5. The Global Fund to Fight AIDS, Tuberculosis and Malaria (The Global Fund):Resource Scenarios 2011-2013: Funding the Global Fight against HIV/AIDS,Tuberculosis and Malaria 2010 [http://www.theglobalfund.org/documents/replenishment/2010/Resource_Scenarios_en.pdf], Accessed 4 August 2010.6. United Nation AIDS Programme (UNAIDS): AIDS epidemic update 2009 2009[http://data.unaids.org/pub/Report/2009/jc1700_epi_update_2009_en.pdf],Accessed 4 August 2010.7. Abdool-Karim Q, Abouzahr C, Dehne K, Mangiaterra V, Moodley J, Rollins N,Say L, Schaffer N, Rosen JE, de Zoysa I: HIV and maternal mortality:turning the tide. Lancet 2010, 375:1948-9.8. International AIDS Society: Environmental scan: mapping HIV researchpriorities for women and children International AIDS Society; 2010 [http://www.iasociety.org/Web/WebContent/File/ILF_Environmental_Scan_July2010.pdf], Accessed 8 July 2010.9. International AIDS Society: Asking the Right Questions: Advancing an HIVResearch Agenda for Women and Children International AIDS Society; 2010[http://www.iasociety.org/Web/WebContent/File/Consensus_Statement_Asking_the_Right_Question_March_2010.pdf],Accessed 8 July 2010.10. Toro PL, Katyal M, Carter RJ, Myer L, El-Sadr WM, Nash D, Abrams EJ: MTCT-Plus Initiative: Initiation of antiretroviral therapy among pregnantwomen in resource-limited countries: CD4+ cell count response andprogram retention. AIDS 2010, 24:515-24.11. Collazos J, Asensi V, Cartón JA: Sex differences in the clinical,immunological and virological parameters of HIV-infected patientstreated with HAART. AIDS 2007, 21:835-43.12. Nicastri E, Leone S, Angeletti C, Palmisano L, Sarmati L, Chiesi A, Geraci A,Vella S, Narciso P, Corpolongo A, Andreoni M: Sex issues in HIV-1-infectedpersons during highly active antiretroviral therapy: a systematic review.J Antimicrob Chemother 2007, 60:724-32.13. Floridia M, Giuliano M, Palmisano L, Vella S: Gender differences in thetreatment of HIV infection. Pharmacol Res 2008, 58:173-82.14. van Leth F, Andrews S, Grinsztejn B, Wilkins E, Lazanas MK, Lange JM,Montaner J, 2NN study group: The effect of baseline CD4 cell count andHIV-1 viral load on the efficacy and safety of nevirapine or efavirenz-based first-line HAART. AIDS 2005, 19:463-71.15. Sanne I, Mommeja-Marin H, Hinkle J, Bartlett JA, Lederman MM, Maartens G,Wakeford C, Shaw A, Quinn J, Gish RG, Rousseau F: Severe hepatotoxicityassociated with nevirapine use in HIV-infected subjects. J Infect Dis 2005,191:825-9.16. Coffie PA, Tonwe-Gold B, Tanon AK, Amani-Bosse C, Bédikou G, Abrams EJ,Dabis F, Ekouevi DK: Incidence and risk factors of severe adverse eventswith nevirapine-based antiretroviral therapy in HIV-infected women.MTCT-Plus program, Abidjan, Côte d’Ivoire. BMC Infect Dis 2010, 10:188.17. Peters P, Stringer J, McConnell MS, Kiarie J, Ratanasuwan W, Intalapaporn P,Potter D, Mutsotso W, Zulu I, Borkowf CB, Bolu O, Brooks JT, Weidle PJ:Nevirapine-associated hepatotoxicity was not predicted by CD4 count>/= 250 cells/μL among women in Zambia, Thailand and Kenya. HIV Med2010, 10:650-60.18. Smith CJ, Sabin CA, Youle MS, Lampe FC, Bhagani S, Madge S,Puradiredja D, Johnson MA, Phillips AN: Response to efavirenz-containingregimens in previously antiretroviral-naive HIV-positive patients: the roleof gender. J Acquir Immune Defic Syndr 2007, 46:62-7.19. Watts DH, Park JG, Cohn SE, Yu S, Hitti J, Stek A, Clax PA, Muderspach L,Lertora JJ: Safety and tolerability of depot medroxyprogesterone acetateamong HIV-infected women on antiretroviral therapy: ACTG A5093.Contraception 2008, 77:84-90.20. Baeten JM, Benki S, Chohan V, Lavreys L, McClelland RS, Mandaliya K,Ndinya-Achola JO, Jaoko W, Overbaugh J: Hormonal contraceptive use,herpes simplex virus infection, and risk of HIV-1 acquisition amongKenyan women. AIDS 2007, 21:1771-77.21. Stringer EM, Levy J, Sinkala M, Chi BH, Matongo I, Chintu N, Stringer JS: HIVdisease progression by hormonal contraceptive method: secondaryanalysis of a randomized trial. AIDS 2009, 23:1377-82.22. Morrison CS, Richardson BA, Mmiro F, Chipato T, Celentano DD, Luoto J,Mugerwa R, Padian N, Rugpao S, Brown JM, Cornelisse P, Salata RA,Hormonal Contraception and the Risk of HIV Acquisition (HC-HIV) StudyGroup: Hormonal contraception and the risk of HIV acquisition. AIDS2007, 21:85-95.23. Polis CB, Wawer MJ, Kiwanuka N, Laeyendecker O, Kagaayi J, Lutalo T,Nalugoda F, Kigozi G, Serwadda D, Gray RH: Effect of hormonalcontraceptive use on HIV progression in female HIV seroconverters inRakai, Uganda. AIDS 2010.24. Roustit M, Jlaiel M, Leclercq P, Stanke-Labesque F: Pharmacokinetics andtherapeutic drug monitoring of antiretrovirals in pregnant women. Br JClin Pharmacol 2008, 66:179-95.25. Fan MD, Maslow BS, Santoro N, Schoenbaum E: HIV and the menopause.Menopause Int 2008, 14:163-8.26. Majaliwa ES, Mohn A, Chiarelli F: Growth and puberty in children with HIVinfection. J Endocrinol Invest 2009, 32:85-90.27. Rakhmanina NY, van den Anker JN, Soldin SJ, van Schaik RH, Mordwinkin N,Neely MN: Can therapeutic drug monitoring improve pharmacotherapyof HIV infection in adolescents? Ther Drug Monit 2010, 32:273-81.28. Beregszaszi M, Dollfus C, Levine M, Faye A, Deghmoun S, Bellal N,Houang M, Chevenne D, Hankard R, Bresson JL, Blanche S, Levy-Marchal C:Longitudinal evaluation and risk factors of lipodystrophy and associatedmetabolic changes in HIV-infected children. J Acquir Immune Defic Syndr2005, 40:161-8.29. Sayles JN, Wong MD, Cunningham WE: The inability to take medicationsopenly at home: does it help explain gender disparities in HAART use? JWomens Health (Larchmt) 2006, 15:173-181.30. Physicians for Human Rights: Epidemic of inequality: women’s rights andHIV/AIDS in Botswana & Swaziland. 2007 [http://physiciansforhumanrights.org/library/documents/reports/botswana-swaziland-report.pdf], Accessed 4August 2010.31. Hejoaka F: Care and secrecy: being a mother of children living with HIVin Burkina Faso. Soc Sci Med 2009, 69:869-76.32. Venkatesh KK, Madiba P, De Bruyn G, Lurie MN, Coates TJ, Gray GE: Whogets tested for HIV in a South African urban township? Implications fortest and treat and gender-based prevention interventions. J AcquirImmune Defic Syndr 2010.33. Mitchell S, Cockcroft A, Lamothe G, Andersson N: Equity in HIV testing:evidence from a cross-sectional study in ten Southern African countries.BMC Int Health Hum Rights 2010, 10:23.34. Le Coeur S, Collins IJ, Pannetier J, Lelièvre E: Gender and access to HIVtesting and antiretroviral treatments in Thailand: why do women havemore and earlier access? Soc Sci Med 2009, 69:846-53.35. Muula AS, Ngulube TJ, Siziya S, Makupe CM, Umar E, Prozesky HW,Wiysonge CS, Mataya RH: Gender distribution of adult patients on highlyactive antiretroviral therapy (HAART) in Southern Africa: a systematicreview. BMC Public Health 2007, 7:63.Karim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 7 of 936. Braitstein P, Boulle A, Nash D, Brinkhof MW, Dabis F, Laurent C,Schechter M, Tuboi SH, Sprinz E, Miotti P, Hosseinipour M, May M, Egger M,Bangsberg DR, Low N: Antiretroviral Therapy in Lower Income Countries(ART-LINC) study group: Gender and the use of antiretroviral treatmentin resource-constrained settings: findings from a multicentercollaboration. J Womens Health (Larchmt) 2008, 17:47-55.37. Horwood C, Haskins L, Vermaak K, Phakathi S, Subbaye R, Doherty T:Prevention of mother to child transmission of HIV (PMTCT) programmein KwaZulu-Natal, South Africa: an evaluation of PMTCT implementationand integration into routine maternal, child and women’s healthservices. Trop Med Int Health 2010, 15:992-99.38. Mofenson LM: Prevention in neglected subpopulations: prevention ofmother-to-child transmission of HIV infection. Clin Infect Dis 2010, 50:S130-48.39. World Health Organization: Towards universal access: scaling up priority HIV/AIDS interventions in the health sector 2010 [http://whqlibdoc.who.int/publications/2010/9789241500395_eng.pdf].40. Shapiro RL, Hughes MD, Ogwu A, Kitch D, Lockman S, Moffat C,Makhema J, Moyo S, Thior I, McIntosh K, van Widenfelt E, Leidner J,Powis K, Asmelash A, Tumbare E, Zwerski S, Sharma U, Handelsman E,Mburu K, Jayeoba O, Moko E, Souda S, Lubega E, Akhtar M, Wester C,Tuomola R, Snowden W, Martinez-Tristani M, Mazhani L, Essex M:Antiretroviral regimens in pregnancy and breast-feeding in Botswana. NEngl J Med 2010, 362:2282-94.41. de Vincenzi I, Kesho Bora Study Group: Triple-antiretroviral prophylaxisduring pregnancy and breastfeeding compared to short- ARVprophylaxis to prevent mother-to-child transmission of HIV-1: the KeshoBora randomized controlled clinical trial in five sites in Burkina Faso,Kenya and South Africa. Programs and Abstracts of the 5th IAS Conferenceon HIV Pathogenesis, Treatment & Prevention: 19-22 July 2009; Cape TownAbstract LBPEC01.42. Chasela CS, Hudgens MG, Jamieson DJ, Kayira D, Hosseinipour MC,Kourtis AP, Martinson F, Tegha G, Knight RJ, Ahmed YI, Kamwendo DD,Hoffman IF, Ellington SR, Kacheche Z, Soko A, Wiener JB, Fiscus SA,Kazembe P, Mofolo IA, Chigwenembe M, Sichali DS, van der Horst CM, BANStudy Group: Maternal or infant antiretroviral drugs to reduce HIV-1transmission. N Engl J Med 2010, 362:2271-81.43. Lallemant M, Jourdain G: Preventing mother-to-child transmission of HIV-protecting this generation and the next. N Engl J Med 2010, 363:1570-2.44. Weidle PJ, Nesheim S: HIV drug resistance and mother-to-childtransmission of HIV. J Clin Perinatol 2010, 37:825-42.45. Strategies for Management of Antiretroviral Therapy (SMART) Study Group,Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD,Neuhaus J, Phillips AN: CD4+ count-guided interruption of antiretroviraltreatment. N Engl J Med 2006, 355:2283-96.46. Strategies for Management of Antiretroviral Therapy (SMART) Study Group,Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD,Neuhaus J, Phillips AN: Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMARTstudy: role of CD4+ cell counts and HIV RNA levels during follow-up. JInfect Dis 2008, 197:1145-55.47. Watts DH, Lu M, Thompson B, Tuomala RE, Meyer WA 3, Mendez H, Rich K,Hanson C, LaRussa P, Diaz C, Mofenson LM: Treatment interruption afterpregnancy: effects on disease progression and laboratory findings. InfectDis Obstet Gynecol 2009, 2009:456717.48. Mahy M, Stover J, Kiragu K, Hayashi C, Akwara P, Luo C, Stanecki K, Ekpini R,Shaffer N: What will it take to achieve virtual elimination of mother-to-child transmission of HIV? An assessment of current progress and futureneeds. Sex Transm Infect 2010, 86:ii48-55.49. Auld AF, Bolu O, Creek T, Lindegren ML, Rivadeneira E, Dale H,Sangrugee N, Ellerbrock T: Potential impact and cost-effectiveness of the2009 “rapid advice” PMTCT guidelines - 15 resource-limited countries,2010. Proceedings of the XVIII International AIDS Conference: 18-23 July 2010;Vienna Abstract WEAE0205.50. Barker PM, Mphatswe W, Rollins N: Antiretroviral drugs in the cupboardare not enough: The impact of health systems’ performance on mother-to-child transmission of HIV. J Acquir Immune Defic Syndr 2010.51. Youngleson MS, Nkurunziza P, Jennings K, Arendse J, Mate KS, Barker P:Improving a mother to child HIV transmission programme throughhealth system redesign: quality improvement, protocol adjustment andresource addition. PLoS One 2010, 5:e13891.52. Horwood C, Haskins L, Vermaak K, Phakathi S, Subbaye R, Doherty T:Prevention of mother to child transmission of HIV (PMTCT) programmein KwaZulu-Natal, South Africa: an evaluation of PMTCT implementationand integration into routine maternal, child and women’s healthservices. Trop Med Int Health 2010.53. Labhardt ND, Manga E, Ndam M, Balo JR, Bischoff A, Stoll B: Earlyassessment of the implementation of a national programme for theprevention of mother-to-child transmission of HIV in Cameroon and theeffects of staff training: a survey in 70 rural health care facilities. TropMed Int Health 2009, 14:288-93.54. Betancourt TS, Abrams EJ, McBain R, Fawzi MC: Family-centred approachesto the prevention of mother to child transmission of HIV. J Int AIDS Soc2010, 13:S2.55. The Antiretroviral Pregnancy Registry: Interim Report 2010 [http://www.apregistry.com/forms/interim_report.pdf], Accessed 1 July 2010.56. Brogly SB, Abzug MJ, Watts DH, Cunningham CK, Williams PL, Oleske J,Conway D, Sperling RS, Spiegel H, Van Dyke RB: Birth defects amongchildren born to human immunodeficiency virus-infected women:pediatric AIDS clinical trials protocols 219 and 219C. Pediatr Infect Dis J2010, 29:421-7.57. Conway D, Scott G, Muenz D, Brogly S, Knapp K, Talbot J, Shapiro D,Read J: Prevalence of congenital anomalies in infants with in uteroexposure to antiretrovirals: IMPAACT P1025. Program and Abstracts of the17th Conference on Retroviruses and Opportunistic Infections: 16-19 February2010 San Francisco;Abstract 923.58. Schulte J, Dominguez K, Sukalac T, Bohannon B, Fowler MG, PediatricSpectrum of HIV Disease Consortium: Declines in low birth weight andpreterm birth among infants who were born to HIV-infected womenduring an era of increased use of maternal antiretroviral drugs: PediatricSpectrum of HIV Disease, 1989-2004. Pediatrics 2007, 119:e900-6.59. Townsend CL, Cortina-Borja M, Peckham CS, Tookey PA: Antiretroviraltherapy and premature delivery in diagnosed HIV-infected women inthe United Kingdom and Ireland. AIDS 2007, 21:1019-26.60. Ekouevi DK, Coffie PA, Becquet R, Tonwe-Gold B, Horo A, Thiebaut R,Leroy V, Blanche S, Dabis F, Abrams EJ: Antiretroviral therapy in pregnantwomen with advanced HIV disease and pregnancy outcomes in Abidjan,Côte d’Ivoire. AIDS 2008, 22:1815-20.61. Briand N, Mandelbrot L, Le Chenadec J, Tubiana R, Teglas JP, Faye A,Dollfus C, Rouzioux C, Blanche S, Warszawski J, ANRS French PerinatalCohort: No relation between in-utero exposure to HAART andintrauterine growth retardation. AIDS 2009, 23:1235-43.62. Kourtis AP, Schmid CH, Jamieson DJ, Lau J: Use of antiretroviral therapy inpregnant HIV-infected women and the risk of premature delivery: ameta-analysis. AIDS 2007, 21:607-15.63. Barret B, Tardieu M, Rustin P, Lacroix C, Chabrol B, Desguerre I, Dollfus C,Mayaux M, Blanche S: Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospectivecohort. AIDS 2003, 17:1769-85.64. Poirier MC, Divi RL, Al-Harthi L, Olivero OA, Nguyen V, Walker B, Landay AL,Walker VE, Charurat M, Blattner WA: Long-term mitochondrial toxicity inHIV-uninfected infants born to HIV-infected mothers. J Acquir ImmuneDefic Syndr 2003, 33:175-83.65. Brogly SB, Foca M, Deville JG, Browning R, Shapiro DE: Potentialconfounding of the association between exposure to nucleosideanalogues and mitochondrial dysfunction in HIV-uninfected andindeterminate infants. J Acquir Immune Defic Syndr 2010, 53:154-7.66. Aldrovandi GM, Chu C, Shearer WT, Li D, Walter J, Thompson B, McIntosh K,Foca M, Meyer WA 3, Ha BF, Rich KC, Moye J Jr: Antiretroviral exposureand lymphocyte mtDNA content among uninfected infants of HIV-1-infected women. Pediatrics 2009, 124:e1189-97.67. Zareba KM, Lavigne JE, Lipshultz SE: Cardiovascular effects of HAART ininfants and children of HIV-infected mothers. Cardiovasc Toxicol 2004,4:271-79.68. Walker VE, Poirier MC: Special issue on health risks of perinatal exposureto nucleoside reverse transcriptase inhibitors. Environ Mol Mutagen 2007,48:159-65.69. Wogan GN: Does perinatal antiretroviral therapy create an iatrogeniccancer risk? Environ Mol Mutagen 2007, 48:210-14.70. Benhammou V, Warszawski J, Bellec S, Doz F, André N, Lacour B, Levine M,Bavoux F, Tubiana R, Mandelbrot L, Clavel J, Blanche S, ANRS-EnquêteKarim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 8 of 9Périnatale Française: Incidence of cancer in children perinatally exposedto nucleoside reverse transcriptase inhibitors. AIDS 2008, 22:2165-77.71. Hankin C, Thorne C, Newell M: Does exposure to antiretroviral therapyaffect growth in the first 18 months of life in uninfected children bornto HIV-infected women? J Acquir Immune Defic Syndr 2005, 40:364-70.72. Williams PL, Marino M, Malee K, Brogly S, Hughes MD, Mofenson LM,PACTG 219C Team: Neurodevelopment and in utero antiretroviralexposure of HIV-exposed uninfected infants. Pediatrics 2010, 125:e250-60.73. Pediatric HIV/AIDS Cohort Study: Surveillance monitoring for ART toxicitiesstudy in HIV-uninfected children born to HIV-infected women (SMARTT Study)National Institute of Child Health and Human Development; 2009 [https://phacs.nichdclinicalstudies.org/publicDocs/SMARTT_Protocol_Version_3.0_December_29_2009_unhighlighted.pdf],Accessed 4 August 2010.74. Joint United Nations Programme on HIV/AIDS (UNAIDS): UNAIDS Report onthe Global AIDS Epidemic 2010 2010 [http://www.unaids.org/globalreport/Global_report.htm], Accessed 23 November 2010.75. Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA, CHER Study Team: Early antiretroviral therapy andmortality among HIV-infected infants. N Engl J Med 2008, 359:2233-44.76. World Health Organization: Report of the WHO Technical Reference Group,Paediatric HIV/ART Care Guideline Group Meeting, 10-11 April 2008 [http://www.who.int/hiv/pub/paediatric/WHO_Paediatric_ART_guideline_rev_mreport_2008.pdf], Accessed 4 August2010.77. Goetghebuer T, Haelterman E, Le Chenadec J, Dollfus C, Gibb D, Judd A,Green H, Galli L, Ramos JT, Giaquinto C, Warszawski J, Levy J, EuropeanInfant Collaboration group: Effect of early antiretroviral therapy on therisk of AIDS/death in HIV-infected infants. AIDS 2009, 23:597-604.78. Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, Madhi SA, Jean-Philippe P, McIntyre JA, CHER Study Team: Early antiretroviral therapy andmortality among HIV-infected infants. N Engl J Med 2008, 359:2233-44.79. Braitstein P, Katshcke A, Shen C, Sang E, Nyandiko W, Ochieng VO,Vreeman R, Yiannoutsos CT, Wools-Kaloustian K, Ayaya S: Retention of HIV-infected and HIV-exposed children in a comprehensive HIV clinical careprogramme in Western Kenya. Trop Med Int Health 2010, 15:833-41.80. Pandian PGDN, Chandran P, Kandasamy C, Gopinath B, Alaudeen SI,Elangovan T, Swaminathan S: Persistance of stunting after HAART in HIV-infected children in south India. Program and Abstracts of the 17thConference on Retroviruses and Opportunistic Infections: 16-19 February 2010San Francisco;Abstract 847.81. Weigel R, Phiri S, Chiputula F, Gumulira J, Brinkhof M, Gsponer T, Tweya H,Egger M, Keiser O: Growth response to antiretroviral treatment in HIV-infected children: a cohort study from Lilongwe, Malawi. Trop Med IntHealth 2010, 15:934-44.82. Sutcliffe CG, van Dijk JH, Bolton C, Persaud D, Moss WJ: Effectiveness ofantiretroviral therapy among HIV-infected children in sub-Saharan Africa.Lancet Infect Dis 2008, 8:477-89.83. Ren Y, Nuttall JJ, Egbers C, Eley BS, Meyers TM, Smith PJ, Maartens G,McIlleron HM: Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis. J Acquir Immune Defic Syndr 2008,47:566-69.84. Moodley M, Reitz C, Fairlie L, Moultrie H, Coovadia A, Kuhn L, Meyers T:Treatment outcomes among HIV-infected infants and young childrenfollowing modifications to protease inhibitor-based therapy due to TBtreatment. Program and Abstracts of the 17th Conference on Retroviruses andOpportunistic Infections: 16-19 February 2010 San Francisco;Abstract 160.85. Palumbo P, Lindsey JC, Hughes MD, Cotton MF, Bobat R, Meyers T,Bwakura-Dangarembizi M, Chi BH, Musoke P, Kamthunzi P, Schimana W,Purdue L, Eshleman SH, Abrams EJ, Millar L, Petzold E, Mofenson LM, Jean-Philippe P, Violari A: Antiretroviral treatment for children with peripartumnevirapine exposure. N Engl J Med 2010, 363:1510-20.86. Lockman S, Shapiro RL, Smeaton LM, Wester C, Thior I, Stevens L, Chand F,Makhema J, Moffat C, Asmelash A, Ndase P, Arimi P, van Widenfelt E,Mazhani L, Novitsky V, Lagakos S, Essex M: Response to antiretroviraltherapy after a single, peripartum dose of nevirapine. N Engl J Med 2007,356:135-47.87. Bowen A, Palasanthiran P, Sohn AH: Global challenges in thedevelopment and delivery of paediatric antiretrovirals. Drug Discov Today2008, 13:530-535.Pre-publication historyThe pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/11/388/prepubdoi:10.1186/1471-2458-11-388Cite this article as: Karim et al.: Asking the right questions: developingevidence-based strategies for treating HIV in women and children. BMCPublic Health 2011 11:388.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submitKarim et al. BMC Public Health 2011, 11:388http://www.biomedcentral.com/1471-2458/11/388Page 9 of 9

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