Figures
Abstract
Introduction
Residents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15–49 years was 12.6%, higher among women (15.3%) than men (8.9%). We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART) in a highly resource-limited setting.
Methods
We studied rates of 2-year mortality and loss to follow-up (LTFU) for children <15 years of age initiating cART between June 2006–July 2011 in 10 rural districts. National guidelines define LTFU as >60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk.
Results
Of 753 children, 29.0% (95% CI: 24.5, 33.2) were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9) were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4) after 90 days on cART and 19.2% (95% CI: 16.0, 22.3) after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3–8.4 g/dL, p<0.01). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV) among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001).
Conclusions
We found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.
Citation: Vermund SH, Blevins M, Moon TD, José E, Moiane L, Tique JA, et al. (2014) Poor Clinical Outcomes for HIV Infected Children on Antiretroviral Therapy in Rural Mozambique: Need for Program Quality Improvement and Community Engagement. PLoS ONE 9(10): e110116. https://doi.org/10.1371/journal.pone.0110116
Editor: David W. Dowdy, Johns Hopkins Bloomberg School of Public Health, United States of America
Received: November 1, 2013; Accepted: September 16, 2014; Published: October 20, 2014
Copyright: © 2014 Vermund et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (grant #U2GPS000631). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. Dr. Tique was supported by the Fogarty AIDS International Training and Research Program, National Institutes of Health #D43TW001035. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: Dr. Vermund is a member of the PLOS ONE editorial board. This does not alter the authors’ adherence to PLOS ONE editorial policies and criteria.
Introduction
Mozambique is one of the most HIV-affected countries with an estimated national HIV prevalence in 2009 of 11.5%, translating into approximately 1.4 million adults living with HIV. [1], [2] Because of its heavy HIV burden, Mozambique is a priority nation for support from the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR). [3] National combination antiretroviral therapy (cART) coverage is low; only an estimated 52% of adults and 20% of children in need of cART were believed to be receiving it as of the end of 2011. [4] In 2010, an estimated 70.8% of pregnant women in their first antenatal care appointment received HIV counseling and testing and 40.2% of HIV-infected pregnant women received ARV prophylaxis for the prevention of mother-to-child transmission (PMTCT), typically single-dose nevirapine [5].
Under 5 (U5) mortality rates have been falling rapidly in Mozambique with 2011 national U5 mortality estimated at 135/1000 live births compared to 219/1000 live births in 1990, in large part because of improvements in vaccination coverage and efforts to manage childhood diarrheal and acute respiratory illnesses. [6] The most recent national estimate is 97/1000 live births, from the latest Demographic Health Survey [7], still shy of the 2015 Millennium Development Goal of 73 deaths per 1000 live births. HIV/AIDS contributes 10% to the U5 mortality nationally [6].
Zambézia Province is a very low-income region of 4.2 million persons in north-central Mozambique whose majority of residents are rural subsistence farmers and fishermen. Zambézia has the nation’s second largest provincial population, representing ≈20% of Mozambique’s total. [1], [8] Provincial HIV prevalence among adults 15–49 years in 2009 was estimated at 12.6% overall, 15.3% among women and 8.9% among men, all higher than national averages, e.g., 13.1% for women 15–49 nationally. [1] Current U5 mortality estimates show Zambézia as having the worst U5 mortality of all provinces, with deaths estimated at 142/1000 live births. [9] Leading causes of U5 deaths in Zambézia in 2009 include neonatal deaths (26.1%), malaria (27.7%) and acute lower respiratory infection (13.7%). HIV/AIDS-related deaths account for 11.5% of U5 deaths in the province [9], [10].
Children with HIV are not in care at as high a proportion as adults with HIV in Africa, and their outcomes are not as good in most programs. [11]–[71] To assess mortality for HIV-infected children on cART, we reviewed data from PEPFAR-supported clinics run by the Zambézia Provincial Health Directorate (Direcção Provincial de Saúde, DPS) in 10 districts where a Vanderbilt University non-governmental organization (NGO) provides technical assistance.
Methods
Both the Mozambican National Bioethics Committee for Health (Comité Nacional de Bioética em Saúde [CNBS]) and the Institutional Review Board of Vanderbilt University approved this analysis. Analysis was performed on routinely collected, de-identified, aggregate patient level data and no individual informed consent was obtained. The CNBS and the Vanderbilt Institutional Review Board explicitly waived the need for written informed consent from the participants.
We analyzed data from a cohort of HIV-infected children <15 years of age initiating cART between June 2006–July 2011 in 10 of 17 rural districts in Zambézia Province. Details of our Friends in Global Health NGO clinical program with the DPS and the Ministry of Health (Ministério de Saúde [MISAU]) have been reported previously. [72] Two districts for which we were responsible did not have electronic medical records at the time of analysis and so were excluded;[73] five additional districts were supported by another NGO in this time period. [74] Patients who transferred from another facility after starting cART were not included in this analysis as data on their care history was incomplete (N = 156).
Patient characteristics at treatment initiation of those alive, lost, and dead at the end of 2 years’ follow-up were compared using rank sum and chi-square tests. Deaths were ascertained from both clinical records and from parental testimonials. Mozambican national guidelines define loss to follow-up (LTFU) as no effective clinical contact within 60 days after the last scheduled medication pickup. [75] Two additional definitions of LTFU from the literature were also applied for the purpose of cross-cohort comparisons. The ‘universal’ definition classifies patients as LTFU if there is no effective clinical contact within 180 days of database closure. [76] The ‘reference’ definition assigns 1 day of follow-up to any individual who does not return following treatment initiation, includes only individuals initiating ART 6 months prior to the database closure, and classifies patients as LTFU if there is no effective clinical contact within 180 days of database closure. [77] All three LTFU definitions deem the patient lost at the date of last contact as opposed to the date of missed visit. Kaplan-Meier estimates were used to compute mortality and the combined endpoint of mortality and LTFU. Cumulative incidence of LTFU was calculated by treating death as a competing risk. Mortality estimates assumed non-informative censoring, i.e., patients LTFU were assumed to have rates of death similar to patients not LTFU. This likely implies that our mortality calculations are under-estimates of true mortality.
Our study did not include children enrolled in HIV care who never initiated treatment. [78] Cotrimoxazole (CTX) data were treated as a tick box for “yes”, collected each visit for the corresponding visit date. If a patient was on CTX anywhere from 0 to 365 days before ART initiation, we considered the patient as “CTX use prior to cART”. If a patient was on CTX anywhere from 90 days before to 90 days after ART initiation, we considered the patient as “current CTX use”.
Results
During five years of PEPFAR support, 753 HIV-infected children <15 years of age initiated cART. Of these children, 678 (90.0%) were <8 years of age at cART initiation, 397 (52.7%) were <2 years, and 191 (25.4%) were <1 years. Girls represented 57% of the pediatric cART patients. Median CD4+ T-lymphocyte cell count (CD4 counts) and percentage (CD4 percentage) at cART initiation were 497 and 15, respectively, although these quantities were missing for 62% and 70% of patients. Nearly half (48%) of children initiated cART very late in their disease progression (WHO stage III or IV), although WHO stage was missing for 58% of patients.
Two years after cART initiation, 152 patients had died and 240 were LTFU. At two years, the estimated probability of death was 29.0% (95% confidence interval [CI] 24.5–33.2), the cumulative incidence of LTFU was 38.7 (95% CI 34.8–42.9), and the probability of either death or LTFU was 62.0% (95% CI 57.6–65.9). We observed substantial heterogeneity between districts in two-year outcomes (Figure 1). Two year LTFU ranged from a district low of 25% to a high of 70% (Fig. 1A; p<0.001), mortality ranged from 16–34% (Fig. 1B; p = 0.19), and death or LTFU ranged from 51.1–88.1% (Fig. 1C; p<0.001). The association between treatment duration and mortality rate did not suggest a marked decline in mortality over time. At 90 days on cART, the mortality rate was 8.4% (95% CI: 6.3, 10.4). At 365 days on cART, the mortality rate was 19.2% (95% CI: 16.0, 22.3) and at 730 days (two years) on cART, the mortality rate was 29.0% (95% CI: 24.5%, 33.2%). Cumulative incidence of LTFU was lower when applying two definitions from the literature. [75] The cumulative incidence of LTFU using the ‘universal’ definition was 26.0% (95% CI 22.6–29.9) at 2 years. [76] The cumulative incidence of LTFU using the ‘reference’ definition was 26.4% (95% CI 22.9–30.2) at 2 years [77].
Table 1 compares patient characteristics at cART initiation between those who were alive, dead, and lost after two years. We did not detect any difference in CD4 counts or percentage at cART initiation in children who were alive and on treatment at 2 years compared to those who were either not alive or not in care at that time (p = 0.6), though we had high rates of missing data. We observed higher hemoglobin at the time of cART initiation among those children alive and on treatment at 2 years (alive: median 9.3 g/dL; 8.3 for dead; 8.4 g/dL for LTFU, p<0.01 for alive vs. dead or LTFU). Any cotrimoxazole use in the year prior to ART initiation was associated with improved 2-year outcomes (alive: 76%, dead: 49%, lost: 55%). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes (alive: 69%, dead: 58%, lost: 59%).
Discussion
The experience from our PEPFAR cART program found that 29% of children initiating cART were dead within two years. It is likely that many of the 39% LTFU are at high risk of death or have already died. HIV care for children is not yet optimized in this impoverished setting with a backdrop of health workforce shortages, poor health care infrastructures, challenging transportation, poor maternal and child health outcomes, high rates of tuberculosis and malaria infections, high levels of malnutrition, low adult and pediatric cART and maternal ARV prophylaxis coverage rates, and limited formal counseling/social support programs. Similar challenges are reported elsewhere, particularly where cART is initiated late and co-infections are already extant. [20], [79], [80] Considerably better outcomes are reported from LMIC outside of Africa. [81]–[92] While a number of pediatric cART programs have reported much better success, we do not know the extent to which there is a reporting bias in the literature, i.e., overrepresentation in the literature of more favorable program outcomes. [11], [44], [60], [64], [65], [68], [69], [85], [93]–[110] Challenges we face have been reported from many low and middle-income nations, though we think our results are especially worrisome [25], [111]–[117].
We observed a wide range of LTFU in different districts, suggesting possible inconsistent fidelity across sites to the active case-finding (busca activa) program that is in place, as well as variations in the quality of care, system infrastructure and/or community engagement. [118] In PMTCT work in Zambia and subsequently in the multinational PEARL study, similar clinic-by-clinic diversity has been seen, documenting that the specific component of the continuum of care that is “broken” in lower functioning clinics may differ by clinic [119]–[123].
In a poorly functioning clinic in Mozambique, we may find health providers who are able to speak only Portuguese with clients, rather than the local language. We have learned from pediatric and obstetric quality improvement work that mothers frequently do not understand complex instructions in Portuguese from health providers who often come from other provinces and may not speak one of the local languages spoken in this ethnically diverse province. [8], [118], [124] On aggregate, Zambézia residents have low health literacy and numeracy rates, likely contributing to patient/caregiver-provider miscommunication and, possibly to LTFU and suboptimal adherence [125].
Another common occurrence in a poorly functioning clinic generally is the failure of pyschosocial services to effectively engage caregivers fully in chronic pediatric care services, as well as HIV services for themselves. Prior to HIV services, long-term follow-up of chronic diseases was not something with which residents of Zambézia Province were familiar. It is common, especially in rural Africa, that asymptomatic or improving children, parents or guardians do not recognize the need for ongoing services. [126]–[132] The same applies to parents themselves; they may be LTFU once they feel better. [72], [78] We have also had anecdotal reports of parents in our program avoiding care for their children (or themselves) due to stigma and fear of persons learning of the HIV infections in their children. These are daunting challenges that call for more effective counseling and trust-building between providers and clients, and potentially for earlier engagement of children in their health care. The active case-finding approach (busca active) of the DPS/MISAU needs serious review and improvement in the face of high mortality and LTFU data in children. It is also possible that traditional active case-finding efforts need to be tailored for special populations, such as children. Improved counseling and family-centered treatment approaches need further exploration. Any innovation in engaging HIV-infected women in their own care can be expected to improve follow-up for their children as well. [133]–[135] A recent review found that although there is evidence of effectiveness of interventions to improve access and adherence to cART, there is less known about major barriers and ways to address them among vulnerable groups such as women, children and adolescents [136].
There is little tradition of long-term pediatric care in rural Zambézia Province. Mothers take children for vaccines and acute illnesses, but only a tuberculosis diagnosis results in chronic care involving long-term drug administration that can reasonably be expected to be available (such medications as insulin and oncology drugs are not available in the rural clinics). In fact, loss to follow-up rates for children with HIV are high throughout southern Africa. [137] Mothers have told us that they and/or their fathers do not want the stigma of having them take the child for HIV care, that they live too far away and cannot afford the time or money for care, they do not know the health workers due to high turnover rates, and that health workers often mistreat them and violate their confidentiality and their privacy [124], [138], [139].
There is evidence from this study and elsewhere that early infant diagnosis, provider initiated testing and counseling, case finding of older children, and family support and outreach are not sufficiently developed in rural Mozambique. [8], [73], [78], [118], [124], [125], [134], [135], [140]–[152] As of 2011, all HIV-infected children <2 years of age should be started on cART as per Mozambican national guidelines, based on results of the South African CHER trial. [79] As of May 2013, Mozambican guidelines changed further to mandate cART for all infected children <5 years of age, independent of clinical status or CD4+ cell count. Yet our study suggests that poor adherence by health workers to standards of screening and HIV staging and subsequent CD4 monitoring impairs pediatric outcomes by delaying recognition of children in need of cART and prophylaxis for opportunistic infections (OI). OI prophylaxis with cotrimoxazole was a protective factor for adverse outcomes in our study. We do not believe that co-trimoxazole benefits are explained by urban-rural differences, as all our sites were rural, nor by family income or assets. All HIV-related services provided by the Ministry, which includes all of the services in this study, are available free of cost, including provision of cotrimoxazole. Family income is not recorded on the clinical record, only patient (or parent) profession; we are thus unable to distinguish subsistence farmers from those who sell their crops, small merchants from larger ones. Over 80 percent of the overall population in the province subsists on less than USD 2 per day as we have documented in a baseline USAID report (Vergara, AE, Blevins M, Vaz LME, et al (2011). Baseline survey report: Improving livelihoods and health of children, women and families in the Province of Zambézia, Republic of Mozambique (available at [http://globalhealth.vanderbilt.edu/programs/scip/]).
Since many children are not diagnosed early or begun on cART early and/or fail to stay in (or adhere to) cART-based care, adverse events are high. [118] We believe that poor interpretation of the guidelines by providers and an overall reluctance to place young children on cART is playing a major role. Quality improvement efforts are essential [148] and are underway to improve infant diagnosis and treatment initiation. [124], [135] Linkages across MCH services are being forged to improve treatment outcomes.
Health worker shortages contribute to poor quality of pediatric care. Given severe health care worker shortages and structural impediments to effective long-term care services, we believe that international support, such as that available from PEPFAR and the Global Fund to Fight AIDS, Tuberculosis and Malaria, will be needed for many years to come. [153]–[157] Whether traditional healers, far more numerous than allopathic practitioners, can be engaged in a productive way for early referral and for assistance in adherence and follow up is unknown. [158], [159] More effective community engagement is essential and some success has been had with church-based outreach. [159], [160] It is also unknown the extent to which efforts such as the Medical Education Partnership Initiative,[161] the Royal Society-DFID Africa Capacity Building Initiative,[162] or the Consortium of New Southern African Medical Schools [163] will make a major difference over the next 5–10 years in addressing chronic health worker shortages in rural Africa. [164]–[167] Task-shifting would be a reasonable approach, but nursing and medical assistants (técnicos de medicina in Mozambique) are also in very short supply. [8] Creative approaches to patient-to-patient adherence and retention show promise [168]–[170].
Our data have limitations that affect the completeness of our study. Missing data were frequent, particularly CD4 counts, CD4%, and WHO stage, limiting our ability to examine delays in initiation of treatment. Multivariable analyses were not performed to estimate independent associations with clinical outcomes due to large amounts of missing data and potential for misclassification among those LTFU. We only ask age (in years) of the child such that age subgroups are less reliable, particularly for younger ages, than if we had reliable birthdate; however, rural populations often do not know specific birthdates. Information on cotrimoxazole use was recorded; however, the nature of the documentation is to record use and thus we are unable to differentiate between non-users and missing data. If data are not missing completely at random, there would be bias in the summary statistics of non-missing data. Generalizability of findings to the whole province was limited because data were available for 10 of the total 17 districts. Our database does not collect information on risk factors for poor clinical outcomes external to the patient visit; prospective data collection on such factors (e.g., health facility staffing, drug stock-outs, family support) would permit more robust risk assessment. Nonetheless, we believe that our data clearly indicate a seriously underperforming pediatric care program in need of aggressive quality improvement; despite limitations, we have found these real-world data to be adequate to guide programmatic improvement and community engagement. These efforts are beginning to bear fruit [124], [135], [148].
There are many challenges not likely to be resolved soon: health care worker shortages and high turnover rates, particularly in remote rural settings, drug and supply stockouts, language barriers, gender-power distortions, literacy and numeracy challenges, poor attitudes of health care workers towards patients, lack of appreciation of the germ theory of disease, crushing rural poverty, poor transportation infrastructures, and structural barriers within the clinical care setting. [73], [78], [146], [148], [153], [171]–[173] Co-infections prevalent in the tropics and food shortages are recurring challenges that are far less prevalent in higher income nations. [174]–[177] Drug resistance has not been studied widely in Mozambique [178].
Even in the face of these obstacles, we and others are having some success in pediatric care HIV quality improvement. [124], [135], [179]–[181] That our real-world findings of co-trimoxazole benefit to children in HIV care reinforces clinical trial results suggesting that HIV-infected children benefit from continued co-trimoxazole (protecting against both malaria and non-malarial disease), even when they are on cART. [182] To better retain children on cART and co-trimoxazole, more comprehensive quality improvement efforts are needed to identify staff, structural, cultural, social and policy challenges and to craft solutions for support to pediatric patients, their caregivers, and health care providers.
Acknowledgments
The authors thank Megan Pask, Wilson Silva, Tito Jequicene, Jairzinho Tereso, Carlos Castel-Branco, Ferreira Ferreira, Kulssum Faque, and Deidra Parrish for their help with this work.
Disclosures: This research was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (grant #U2GPS000631). The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the CDC. Dr. Tique was supported by the Fogarty AIDS International Training and Research Program, National Institutes of Health #D43TW001035).
Author Contributions
Conceived and designed the experiments: SHV MB TDM EJ BES LMEV. Performed the experiments: MB TDM EJ LM JAT MS LMEV. Analyzed the data: SHV MB BES LMEV. Contributed reagents/materials/analysis tools: SHV MB TDM EJ LM LMEV. Wrote the paper: SHV MB TDM BES LMEV. Edited and improved the paper: SHV MB TDM EJ LM JAT MS PJC BES LMEV.
References
- 1.
Ministério da Saúde Instituto Nacional de Saúde (INS), Instituto Nacional de Estatística (INE), ICF Macro (2010) Inquérito Nacional de Prevalência, Riscos Comportamentais e Informação sobre o HIV e SIDA (INSIDA) em Moçambique 2009. Calverton, Maryland, EUA: INS, INE, e ICF Macro.
- 2. Auld AF, Mbofana F, Shiraishi RW, Sanchez M, Alfredo C, et al. (2011) Four-year treatment outcomes of adult patients enrolled in Mozambique’s rapidly expanding antiretroviral therapy program. PLoS One 6: e18453.
- 3.
U.S. State Department (2011) The United States President’s Emergency Plan for AIDS Relief.
- 4.
Republic of Mozambique, National AIDS Council, CNCS (2012) 2012 Global AIDS Response Progress Report for the Period 2010–2011. Mozambique: Ministério da Saúde Instituto Nacional de Saúde (INS).
- 5.
National Public Health Directorate MoH, Republic of Mozambique (2011) Preliminary Report of the National Evaluation of the Prevention of Mother-to-Child Transmission Program.
- 6.
WHO (2012) Partnership for Maternal, Newborn & Child Health, World Health Organization. Countdown to 2015: Building a Future for Women and Children, Mozambique Country Reports.
- 7.
Instituto Nacional de Estastistica, Ministerio da Saude, US AID (2013) Moçambique Inquérito Demográfico e de Saúde 2011. Calverton, Maryland, USA.
- 8. Audet CM, Burlison J, Moon TD, Sidat M, Vergara AE, et al. (2010) Sociocultural and epidemiological aspects of HIV/AIDS in Mozambique. BMC Int Health Hum Rights 10: 15.
- 9.
Institute NS (2009) Preliminary Report on the Multiple Indicator Cluster Survey, 2008. Maputo, Mozambique.
- 10.
Republic of Mozambique, Ministry of Health, National Institute of Health (2009) Mozambique National Child Mortality Study 2009 Summary.
- 11. Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, Chintu N, Stringer EM, et al. (2007) Clinical outcomes and CD4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. JAMA 298: 1888–1899.
- 12. Bland RM, Ndirangu J, Newell ML (2013) Maximising opportunities for increased antiretroviral treatment in children in an existing HIV programme in rural South Africa. BMJ 346: f550.
- 13. Patel SD, Larson E, Mbengashe T, O’Bra H, Brown JW, et al. (2012) Increases in pediatric antiretroviral treatment, South Africa 2005–2010. PLoS One 7: e44914.
- 14. Munyagwa M, Baisley K, Levin J, Brian M, Grosskurth H, et al. (2012) Mortality of HIV-infected and uninfected children in a longitudinal cohort in rural south-west Uganda during 8 years of follow-up. Trop Med Int Health 17: 836–843.
- 15. Meyers T, Dramowski A, Schneider H, Gardiner N, Kuhn L, et al. (2012) Changes in pediatric HIV-related hospital admissions and mortality in Soweto, South Africa, 1996–2011: light at the end of the tunnel? J Acquir Immune Defic Syndr 60: 503–510.
- 16. Johnson LF, Davies MA, Moultrie H, Sherman GG, Bland RM, et al. (2012) The effect of early initiation of antiretroviral treatment in infants on pediatric AIDS mortality in South Africa: a model-based analysis. Pediatr Infect Dis J 31: 474–480.
- 17. Bland RM (2011) Management of HIV-infected children in Africa: progress and challenges. Arch Dis Child 96: 911–915.
- 18. Eley B (2006) Addressing the paediatric HIV epidemic: a perspective from the Western Cape Region of South Africa. Trans R Soc Trop Med Hyg 100: 19–23.
- 19. De Baets AJ, Bulterys M, Abrams EJ, Kankassa C, Pazvakavambwa IE (2007) Care and treatment of HIV-infected children in Africa: issues and challenges at the district hospital level. Pediatr Infect Dis J 26: 163–173.
- 20. Braitstein P, Nyandiko W, Vreeman R, Wools-Kaloustian K, Sang E, et al. (2009) The clinical burden of tuberculosis among human immunodeficiency virus-infected children in Western Kenya and the impact of combination antiretroviral treatment. Pediatr Infect Dis J 28: 626–632.
- 21. Nicoll A, Timaeus I, Kigadye RM, Walraven G, Killewo J (1994) The impact of HIV-1 infection on mortality in children under 5 years of age in sub-Saharan Africa: a demographic and epidemiologic analysis. AIDS 8: 995–1005.
- 22. Martinson NA, Moultrie H, van Niekerk R, Barry G, Coovadia A, et al. (2009) HAART and risk of tuberculosis in HIV-infected South African children: a multi-site retrospective cohort. Int J Tuberc Lung Dis 13: 862–867.
- 23. Sutcliffe CG, van Dijk JH, Bolton-Moore C, Cotham M, Tambatamba B, et al. (2010) Differences in presentation, treatment initiation, and response among children infected with human immunodeficiency virus in urban and rural Zambia. Pediatr Infect Dis J 29: 849–854.
- 24. Sutcliffe CG, van Dijk JH, Bolton C, Persaud D, Moss WJ (2008) Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa. Lancet Infect Dis 8: 477–489.
- 25. van Dijk JH, Sutcliffe CG, Munsanje B, Hamangaba F, Thuma PE, et al. (2009) Barriers to the care of HIV-infected children in rural Zambia: a cross-sectional analysis. BMC Infect Dis 9: 169.
- 26. Feucht UD, Kinzer M, Kruger M (2007) Reasons for delay in initiation of antiretroviral therapy in a population of HIV-infected South African children. J Trop Pediatr 53: 398–402.
- 27. Thomas TA, Shenoi SV, Heysell SK, Eksteen FJ, Sunkari VB, et al. (2010) Extensively drug-resistant tuberculosis in children with human immunodeficiency virus in rural South Africa. Int J Tuberc Lung Dis 14: 1244–1251.
- 28. Adjorlolo-Johnson G, Wahl Uheling A, Ramachandran S, Strasser S, Kouakou J, et al. (2013) Scaling up pediatric HIV care and treatment in Africa: clinical site characteristics associated with favorable service utilization. J Acquir Immune Defic Syndr 62: e7–e13.
- 29. Kabue MM, Buck WC, Wanless SR, Cox CM, McCollum ED, et al. (2012) Mortality and clinical outcomes in HIV-infected children on antiretroviral therapy in Malawi, Lesotho, and Swaziland. Pediatrics 130: e591–599.
- 30. Okomo U, Togun T, Oko F, Peterson K, Townend J, et al. (2012) Treatment outcomes among HIV-1 and HIV-2 infected children initiating antiretroviral therapy in a concentrated low prevalence setting in West Africa. BMC Pediatr 12: 95.
- 31. Grimwood A, Fatti G, Mothibi E, Malahlela M, Shea J, et al. (2012) Community adherence support improves programme retention in children on antiretroviral treatment: a multicentre cohort study in South Africa. J Int AIDS Soc 15: 17381.
- 32. Chhagan MK, Kauchali S, Van den Broeck J (2012) Clinical and contextual determinants of anthropometric failure at baseline and longitudinal improvements after starting antiretroviral treatment among South African children. Trop Med Int Health 17: 1092–1099.
- 33. Satti H, McLaughlin MM, Omotayo DB, Keshavjee S, Becerra MC, et al. (2012) Outcomes of comprehensive care for children empirically treated for multidrug-resistant tuberculosis in a setting of high HIV prevalence. PLoS One 7: e37114.
- 34. Laughton B, Cornell M, Grove D, Kidd M, Springer PE, et al. (2012) Early antiretroviral therapy improves neurodevelopmental outcomes in infants. AIDS 26: 1685–1690.
- 35. Haberer JE, Kiwanuka J, Nansera D, Ragland K, Mellins C, et al. (2012) Multiple measures reveal antiretroviral adherence successes and challenges in HIV-infected Ugandan children. PLoS One 7: e36737.
- 36. Kekitiinwa A, Asiimwe AR, Kasirye P, Korutaro V, Kitaka S, et al. (2012) Prospective long-term outcomes of a cohort of Ugandan children with laboratory monitoring during antiretroviral therapy. Pediatr Infect Dis J 31: e117–125.
- 37. Musiime V, Kayiwa J, Kiconco M, Tamale W, Alima H, et al. (2012) Response to antiretroviral therapy of HIV type 1-infected children in urban and rural settings of Uganda. AIDS Res Hum Retroviruses 28: 1647–1657.
- 38. Workneh G, Scherzer L, Kirk B, Draper HR, Anabwani G, et al. (2013) Evaluation of the effectiveness of an outreach clinical mentoring programme in support of paediatric HIV care scale-up in Botswana. AIDS Care 25: 11–19.
- 39. Heidari S, Mofenson LM, Hobbs CV, Cotton MF, Marlink R, et al. (2012) Unresolved antiretroviral treatment management issues in HIV-infected children. J Acquir Immune Defic Syndr 59: 161–169.
- 40. Kim MH, Cox C, Dave A, Draper HR, Kabue M, et al. (2012) Prompt initiation of ART With therapeutic food is associated with improved outcomes in HIV-infected Malawian children with malnutrition. J Acquir Immune Defic Syndr 59: 173–176.
- 41. Zyl GU, Rabie H, Nuttall JJ, Cotton MF (2011) It is time to consider third-line options in antiretroviral-experienced paediatric patients? J Int AIDS Soc 14: 55.
- 42. Reubenson G (2011) Pediatric drug-resistant tuberculosis: a global perspective: a global perspective. Paediatr Drugs 13: 349–355.
- 43. Geddes R, Giddy J, Butler LM, Van Wyk E, Crankshaw T, et al. (2011) Dual and triple therapy to prevent mother-to-child transmission of HIV in a resource-limited setting - lessons from a South African programme. S Afr Med J 101: 651–654.
- 44. Fatti G, Bock P, Eley B, Mothibi E, Grimwood A (2011) Temporal trends in baseline characteristics and treatment outcomes of children starting antiretroviral treatment: an analysis in four provinces in South Africa, 2004–2009. J Acquir Immune Defic Syndr 58: e60–67.
- 45. Ahoua L, Guenther G, Rouzioux C, Pinoges L, Anguzu P, et al. (2011) Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda. BMC Pediatr 11: 67.
- 46. Desmonde S, Coffie P, Aka E, Amani-Bosse C, Messou E, et al. (2011) Severe morbidity and mortality in untreated HIV-infected children in a paediatric care programme in Abidjan, Cote d’Ivoire, 2004–2009. BMC Infect Dis 11: 182.
- 47. Ciaranello AL, Perez F, Maruva M, Chu J, Engelsmann B, et al. (2011) WHO 2010 guidelines for prevention of mother-to-child HIV transmission in Zimbabwe: modeling clinical outcomes in infants and mothers. PLoS One 6: e20224.
- 48. Bakanda C, Birungi J, Mwesigwa R, Nachega JB, Chan K, et al. (2011) Survival of HIV-infected adolescents on antiretroviral therapy in Uganda: findings from a nationally representative cohort in Uganda. PLoS One 6: e19261.
- 49. Schneider K, Puthanakit T, Kerr S, Law MG, Cooper DA, et al. (2011) Economic evaluation of monitoring virologic responses to antiretroviral therapy in HIV-infected children in resource-limited settings. AIDS 25: 1143–1151.
- 50. Frohoff C, Moodley M, Fairlie L, Coovadia A, Moultrie H, et al. (2011) Antiretroviral therapy outcomes in HIV-infected children after adjusting protease inhibitor dosing during tuberculosis treatment. PLoS One 6: e17273.
- 51. De Maayer T, Saloojee H (2011) Clinical outcomes of severe malnutrition in a high tuberculosis and HIV setting. Arch Dis Child 96: 560–564.
- 52. McCollum ED, Preidis GA, Golitko CL, Siwande LD, Mwansambo C, et al. (2011) Routine inpatient human immunodeficiency virus testing system increases access to pediatric human immunodeficiency virus care in sub-Saharan Africa. Pediatr Infect Dis J 30: e75–81.
- 53. Ndondoki C, Dabis F, Namale L, Becquet R, Ekouevi D, et al. (2011) [Survival, clinical and biological outcomes of HIV-infected children treated by antiretroviral therapy in Africa: systematic review, 2004–2009]. Presse Med 40: e338–357.
- 54. Peacock-Villada E, Richardson BA, John-Stewart GC (2011) Post-HAART outcomes in pediatric populations: comparison of resource-limited and developed countries. Pediatrics 127: e423–441.
- 55. Fatti G, Bock P, Grimwood A, Eley B (2010) Increased vulnerability of rural children on antiretroviral therapy attending public health facilities in South Africa: a retrospective cohort study. J Int AIDS Soc 13: 46.
- 56. Buck WC, Kabue MM, Kazembe PN, Kline MW (2010) Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children. J Int AIDS Soc 13: 31.
- 57. Musoke PM, Mudiope P, Barlow-Mosha LN, Ajuna P, Bagenda D, et al. (2010) Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study. BMC Pediatr 10: 56.
- 58. Sutcliffe CG, Bolton-Moore C, van Dijk JH, Cotham M, Tambatamba B, et al. (2010) Secular trends in pediatric antiretroviral treatment programs in rural and urban Zambia: a retrospective cohort study. BMC Pediatr 10: 54.
- 59. Nyandiko WM, Mwangi A, Ayaya SO, Nabakwe EC, Tenge CN, et al. (2009) Characteristics of HIV-infected children seen in Western Kenya. East Afr Med J 86: 364–373.
- 60. Sauvageot D, Schaefer M, Olson D, Pujades-Rodriguez M, O’Brien DP (2010) Antiretroviral therapy outcomes in resource-limited settings for HIV-infected children <5 years of age. Pediatrics 125: e1039–1047.
- 61. Davies MA, Keiser O, Technau K, Eley B, Rabie H, et al. (2009) Outcomes of the South African National Antiretroviral Treatment Programme for children: the IeDEA Southern Africa collaboration. S Afr Med J 99: 730–737.
- 62. Leyenaar JK, Novosad PM, Ferrer KT, Thahane LK, Mohapi EQ, et al. (2010) Early clinical outcomes in children enrolled in human immunodeficiency virus infection care and treatment in lesotho. Pediatr Infect Dis J 29: 340–345.
- 63. Ciaranello AL, Chang Y, Margulis AV, Bernstein A, Bassett IV, et al. (2009) Effectiveness of pediatric antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Clin Infect Dis 49: 1915–1927.
- 64. Janssen N, Ndirangu J, Newell ML, Bland RM (2010) Successful paediatric HIV treatment in rural primary care in Africa. Arch Dis Child 95: 414–421.
- 65. Memirie ST (2009) Clinical outcome of children on HAART at police referral hospital, Addis Ababa, Ethiopia. Ethiop Med J 47: 159–164.
- 66. Ntanda H, Olupot-Olupot P, Mugyenyi P, Kityo C, Lowes R, et al. (2009) Orphanhood predicts delayed access to care in Ugandan children. Pediatr Infect Dis J 28: 153–155.
- 67. Van Winghem J, Telfer B, Reid T, Ouko J, Mutunga A, et al. (2008) Implementation of a comprehensive program including psycho-social and treatment literacy activities to improve adherence to HIV care and treatment for a pediatric population in Kenya. BMC Pediatr 8: 52.
- 68. Kiboneka A, Wangisi J, Nabiryo C, Tembe J, Kusemererwa S, et al. (2008) Clinical and immunological outcomes of a national paediatric cohort receiving combination antiretroviral therapy in Uganda. AIDS 22: 2493–2499.
- 69. Jaspan HB, Berrisford AE, Boulle AM (2008) Two-year outcomes of children on non-nucleoside reverse transcriptase inhibitor and protease inhibitor regimens in a South African pediatric antiretroviral program. Pediatr Infect Dis J 27: 993–998.
- 70. Bock P, Boulle A, White C, Osler M, Eley B (2008) Provision of antiretroviral therapy to children within the public sector of South Africa. Trans R Soc Trop Med Hyg 102: 905–911.
- 71. Walker AS, Ford D, Mulenga V, Thomason MJ, Nunn A, et al. (2009) Adherence to both cotrimoxazole and placebo is associated with improved survival among HIV-infected Zambian children. AIDS Behav 13: 33–41.
- 72. Moon TD, Burlison JR, Sidat M, Pires P, Silva W, et al. (2010) Lessons Learned while Implementing an HIV/AIDs Care and Treatment Program in Rural Mozambique. Retrovirology: Research and Treatment 3: 1.
- 73. Manders EJ, Jose E, Solis M, Burlison J, Nhampossa JL, et al. (2010) Implementing OpenMRS for patient monitoring in an HIV/AIDS care and treatment program in rural Mozambique. Stud Health Technol Inform 160: 411–415.
- 74. Lahuerta M, Lima J, Elul B, Okamura M, Alvim MF, et al. (2011) Patients enrolled in HIV care in Mozambique: baseline characteristics and follow-up outcomes. J Acquir Immune Defic Syndr 58: e75–86.
- 75.
Shepherd BE, Blevins M, Vaz LM, Moon TD, Kipp AM, et al.. (2013) Impact of Definitions of Loss to Follow-up on Estimates of Retention, Disease Progression, and Mortality: Application to an HIV Program in Mozambique. Am J Epidemiol.
- 76. Chi BH, Yiannoutsos CT, Westfall AO, Newman JE, Zhou J, et al. (2011) Universal definition of loss to follow-up in HIV treatment programs: a statistical analysis of 111 facilities in Africa, Asia, and Latin America. PLoS Med 8: e1001111.
- 77.
Grimsrud AT, Cornell M, Egger M, Boulle A, Myer L (2013) Impact of definitions of loss to follow-up (LTFU) in antiretroviral therapy program evaluation: variation in the definition can have an appreciable impact on estimated proportions of LTFU. J Clin Epidemiol.
- 78. Moon TD, Burlison JR, Blevins M, Shepherd BE, Baptista A, et al. (2011) Enrolment and programmatic trends and predictors of antiretroviral therapy initiation from president’s emergency plan for AIDS Relief (PEPFAR)-supported public HIV care and treatment sites in rural Mozambique. Int J STD AIDS 22: 621–627.
- 79. Violari A, Cotton MF, Gibb DM, Babiker AG, Steyn J, et al. (2008) Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med 359: 2233–2244.
- 80. Ylitalo N, Brogly S, Hughes MD, Nachman S, Dankner W, et al. (2006) Risk factors for opportunistic illnesses in children with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Pediatr Adolesc Med 160: 778–787.
- 81. Rath BA, von Kleist M, Castillo ME, Kolevic L, Caballero P, et al. (2013) Antiviral resistance and correlates of virologic failure in the first cohort of HIV-infected children gaining access to structured antiretroviral therapy in Lima, Peru: a cross-sectional analysis. BMC Infect Dis 13: 1.
- 82. Christie CD, Pierre RB (2012) Eliminating vertically-transmitted HIV/AIDS while improving access to treatment and care for women, children and adolescents in Jamaica. West Indian Med J 61: 396–404.
- 83. Hansudewechakul R, Naiwatanakul T, Katana A, Faikratok W, Lolekha R, et al. (2012) Successful clinical outcomes following decentralization of tertiary paediatric HIV care to a community-based paediatric antiretroviral treatment network, Chiangrai, Thailand, 2002 to 2008. J Int AIDS Soc 15: 17358.
- 84. Diniz LM, Maia MM, Camargos LS, Amaral LC, Goulart EM, et al. (2011) Impact of HAART on growth and hospitalization rates among HIV-infected children. J Pediatr (Rio J) 87: 131–137.
- 85. Lumbiganon P, Kariminia A, Aurpibul L, Hansudewechakul R, Puthanakit T, et al. (2011) Survival of HIV-infected children: a cohort study from the Asia-Pacific region. J Acquir Immune Defic Syndr 56: 365–371.
- 86. Oliveira R, Krauss M, Essama-Bibi S, Hofer C, Robert Harris D, et al. (2010) Viral load predicts new world health organization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy, independent of CD4 T lymphocyte value. Clin Infect Dis 51: 1325–1333.
- 87. Rodriguez de Schiavi MS, Scrigni A, Garcia Arrigoni P, Bologna R, Barboni G, et al. (2009) [Highly active antiretroviral therapy in HIV sero-positive children. Disease progression by baseline clinical, immunological and virological status]. Arch Argent Pediatr 107: 212–220.
- 88. Prasitsuebsai W, Bowen AC, Pang J, Hesp C, Kariminia A, et al. (2010) Pediatric HIV clinical care resources and management practices in Asia: a regional survey of the TREAT Asia pediatric network. AIDS Patient Care STDS 24: 127–131.
- 89. McConnell MS, Chasombat S, Siangphoe U, Yuktanont P, Lolekha R, et al. (2010) National program scale-up and patient outcomes in a pediatric antiretroviral treatment program, Thailand, 2000–2007. J Acquir Immune Defic Syndr 54: 423–429.
- 90. Souza E, Santos N, Valentini S, Silva G, Falbo A (2010) Long-term follow-up outcomes of perinatally HIV-infected adolescents: infection control but school failure. J Trop Pediatr 56: 421–426.
- 91. Kumarasamy N, Venkatesh KK, Devaleenol B, Poongulali S, Mothi SN, et al. (2009) Safety, tolerability and effectiveness of generic HAART in HIV-infected children in South India. J Trop Pediatr 55: 155–159.
- 92. Noel F, Mehta S, Zhu Y, Rouzier Pde M, Marcelin A, et al. (2008) Improving outcomes in infants of HIV-infected women in a developing country setting. PLoS One 3: e3723.
- 93. Reddi A, Leeper SC, Grobler AC, Geddes R, France KH, et al. (2007) Preliminary outcomes of a paediatric highly active antiretroviral therapy cohort from KwaZulu-Natal, South Africa. BMC Pediatr 7: 13.
- 94. Puthanakit T, Aurpibul L, Oberdorfer P, Akarathum N, Kanjananit S, et al. (2007) Hospitalization and mortality among HIV-infected children after receiving highly active antiretroviral therapy. Clin Infect Dis 44: 599–604.
- 95. Puthanakit T, Oberdorfer A, Akarathum N, Kanjanavanit S, Wannarit P, et al. (2005) Efficacy of highly active antiretroviral therapy in HIV-infected children participating in Thailand’s National Access to Antiretroviral Program. Clin Infect Dis 41: 100–107.
- 96. Janssens B, Raleigh B, Soeung S, Akao K, Te V, et al. (2007) Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia. Pediatrics 120: e1134–1140.
- 97. Nyandiko WM, Ayaya S, Nabakwe E, Tenge C, Sidle JE, et al. (2006) Outcomes of HIV-infected orphaned and non-orphaned children on antiretroviral therapy in western Kenya. J Acquir Immune Defic Syndr 43: 418–425.
- 98. Wamalwa DC, Obimbo EM, Farquhar C, Richardson BA, Mbori-Ngacha DA, et al. (2010) Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort. BMC Pediatr 10: 33.
- 99. O’Brien DP, Sauvageot D, Zachariah R, Humblet P, Medecins Sans F (2006) In resource-limited settings good early outcomes can be achieved in children using adult fixed-dose combination antiretroviral therapy. AIDS 20: 1955–1960.
- 100. Adje-Toure C, Hanson DL, Talla-Nzussouo N, Borget MY, Kouadio LY, et al. (2008) Virologic and immunologic response to antiretroviral therapy and predictors of HIV type 1 drug resistance in children receiving treatment in Abidjan, Cote d’Ivoire. AIDS Res Hum Retroviruses 24: 911–917.
- 101. Song R, Jelagat J, Dzombo D, Mwalimu M, Mandaliya K, et al. (2007) Efficacy of highly active antiretroviral therapy in HIV-1 infected children in Kenya. Pediatrics 120: e856–861.
- 102. Kline MW, Matusa RF, Copaciu L, Calles NR, Kline NE, et al. (2004) Comprehensive pediatric human immunodeficiency virus care and treatment in Constanta, Romania: implementation of a program of highly active antiretroviral therapy in a resource-poor setting. Pediatr Infect Dis J 23: 695–700.
- 103. Kabue MM, Kekitiinwa A, Maganda A, Risser JM, Chan W, et al. (2008) Growth in HIV-infected children receiving antiretroviral therapy at a pediatric infectious diseases clinic in Uganda. AIDS Patient Care STDS 22: 245–251.
- 104. Kline MW, Rugina S, Ilie M, Matusa RF, Schweitzer AM, et al. (2007) Long-term follow-up of 414 HIV-infected Romanian children and adolescents receiving lopinavir/ritonavir-containing highly active antiretroviral therapy. Pediatrics 119: e1116–1120.
- 105. Evans-Gilbert T, Pierre R, Steel-Duncan JC, Rodriguez B, Whorms S, et al. (2004) Antiretroviral drug therapy in HIV-infected Jamaican children. West Indian Med J 53: 322–326.
- 106. Pierre RB, Steel-Duncan JC, Evans-Gilbert T, Rodriguez B, Moore J, et al. (2008) Effectiveness of antiretroviral therapy in treating paediatric HIV/AIDS in Jamaica. West Indian Med J 57: 223–230.
- 107. Eley B, Davies MA, Apolles P, Cowburn C, Buys H, et al. (2006) Antiretroviral treatment for children. S Afr Med J 96: 988–993.
- 108. Collins IJ, Jourdain G, Hansudewechakul R, Kanjanavanit S, Hongsiriwon S, et al. (2010) Long-term survival of HIV-infected children receiving antiretroviral therapy in Thailand: a 5-year observational cohort study. Clin Infect Dis 51: 1449–1457.
- 109. Meyers TM, Yotebieng M, Kuhn L, Moultrie H (2011) Antiretroviral therapy responses among children attending a large public clinic in Soweto, South Africa. Pediatr Infect Dis J 30: 974–979.
- 110. van Kooten Niekerk NK, Knies MM, Howard J, Rabie H, Zeier M, et al. (2006) The first 5 years of the family clinic for HIV at Tygerberg Hospital: family demographics, survival of children and early impact of antiretroviral therapy. J Trop Pediatr 52: 3–11.
- 111. Kamya MR, Mayanja-Kizza H, Kambugu A, Bakeera-Kitaka S, Semitala F, et al. (2007) Predictors of long-term viral failure among ugandan children and adults treated with antiretroviral therapy. J Acquir Immune Defic Syndr 46: 187–193.
- 112. Zanoni BC, Phungula T, Zanoni HM, France H, Feeney ME (2011) Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa. PLoS One 6: e22706.
- 113. Bong CN, Yu JK, Chiang HC, Huang WL, Hsieh TC, et al. (2007) Risk factors for early mortality in children on adult fixed-dose combination antiretroviral treatment in a central hospital in Malawi. AIDS 21: 1805–1810.
- 114. Callens SF, Shabani N, Lusiama J, Lelo P, Kitetele F, et al. (2009) Mortality and associated factors after initiation of pediatric antiretroviral treatment in the Democratic Republic of the Congo. Pediatr Infect Dis J 28: 35–40.
- 115. Raguenaud ME, Isaakidis P, Zachariah R, Te V, Soeung S, et al. (2009) Excellent outcomes among HIV+ children on ART, but unacceptably high pre-ART mortality and losses to follow-up: a cohort study from Cambodia. BMC Pediatr 9: 54.
- 116. Taye B, Shiferaw S, Enquselassie F (2010) The impact of malnutrition in survival of HIV infected children after initiation of antiretroviral treatment (ART). Ethiop Med J 48: 1–10.
- 117. Anaky MF, Duvignac J, Wemin L, Kouakoussui A, Karcher S, et al. (2010) Scaling up antiretroviral therapy for HIV-infected children in Cote d’Ivoire: determinants of survival and loss to programme. Bull World Health Organ 88: 490–499.
- 118. Groh K, Audet CM, Baptista A, Sidat M, Vergara A, et al. (2011) Barriers to antiretroviral therapy adherence in rural Mozambique. BMC Public Health 11: 650.
- 119. Stringer EM, Sinkala M, Stringer JS, Mzyece E, Makuka I, et al. (2003) Prevention of mother-to-child transmission of HIV in Africa: successes and challenges in scaling-up a nevirapine-based program in Lusaka, Zambia. AIDS 17: 1377–1382.
- 120. Stringer JS, Sinkala M, Maclean CC, Levy J, Kankasa C, et al. (2005) Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia. AIDS 19: 1309–1315.
- 121. Reithinger R, Megazzini K, Durako SJ, Harris DR, Vermund SH (2007) Monitoring and evaluation of programmes to prevent mother to child transmission of HIV in Africa. BMJ 334: 1143–1146.
- 122. Stringer EM, Ekouevi DK, Coetzee D, Tih PM, Creek TL, et al. (2010) Coverage of nevirapine-based services to prevent mother-to-child HIV transmission in 4 African countries. JAMA 304: 293–302.
- 123. Stringer EM, Chintu NT, Levy JW, Sinkala M, Chi BH, et al. (2008) Declining HIV prevalence among young pregnant women in Lusaka, Zambia. Bull World Health Organ 86: 697–702.
- 124. Ciampa PJ, Burlison JR, Blevins M, Sidat M, Moon TD, et al. (2011) Improving retention in the early infant diagnosis of HIV program in rural Mozambique by better service integration. J Acquir Immune Defic Syndr 58: 115–119.
- 125. Ciampa PJ, Vaz LM, Blevins M, Sidat M, Rothman RL, et al. (2012) The association among literacy, numeracy, HIV knowledge and health-seeking behavior: a population-based survey of women in rural Mozambique. PLoS One 7: e39391.
- 126. Nyandiko W, Vreeman R, Liu H, Shangani S, Sang E, et al. (2013) Nonadherence to clinic appointments among HIV-infected children in an ambulatory care program in western Kenya. J Acquir Immune Defic Syndr 63: e49–55.
- 127. Sengayi M, Dwane N, Marinda E, Sipambo N, Fairlie L, et al. (2013) Predictors of loss to follow-up among children in the first and second years of antiretroviral treatment in Johannesburg, South Africa. Glob Health Action 6: 19248.
- 128. Wachira J, Middlestadt SE, Vreeman R, Braitstein P (2012) Factors underlying taking a child to HIV care: implications for reducing loss to follow-up among HIV-infected and -exposed children. SAHARA J 9: 20–29.
- 129. Langat NT, Odero W, Gatongi P (2012) Antiretroviral drug adherence by HIV infected children attending Kericho District Hospital, Kenya. East Afr J Public Health 9: 101–104.
- 130.
McNairy ML, Lamb MR, Carter RJ, Fayorsey R, Tene G, et al.. (2012) Retention of HIV-infected children on antiretroviral treatment in HIV care and treatment programs in Kenya, Mozambique, Rwanda and Tanzania. J Acquir Immune Defic Syndr.
- 131. Okomo U, Togun T, Oko F, Peterson K, Jaye A (2012) Mortality and loss to programme before antiretroviral therapy among HIV-infected children eligible for treatment in The Gambia, West Africa. AIDS Res Ther 9: 28.
- 132. Chetty T, Knight S, Giddy J, Crankshaw TL, Butler LM, et al. (2012) A retrospective study of Human Immunodeficiency Virus transmission, mortality and loss to follow-up among infants in the first 18 months of life in a prevention of mother-to-child transmission programme in an urban hospital in KwaZulu-Natal, South Africa. BMC Pediatr 12: 146.
- 133. Audet CM, Silva Matos C, Blevins M, Cardoso A, Moon TD, et al. (2012) Acceptability of cervical cancer screening in rural Mozambique. Health Educ Res 27: 544–551.
- 134. Moon TD, Silva-Matos C, Cordoso A, Baptista AJ, Sidat M, et al. (2012) Implementation of cervical cancer screening using visual inspection with acetic acid in rural Mozambique: successes and challenges using HIV care and treatment programme investments in Zambezia Province. J Int AIDS Soc 15: 17406.
- 135. Ciampa PJ, Tique JA, Juma N, Sidat M, Moon TD, et al. (2012) Addressing poor retention of infants exposed to HIV: a quality improvement study in rural Mozambique. J Acquir Immune Defic Syndr 60: e46–52.
- 136. Scanlon ML, Vreeman RC (2013) Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings. HIV AIDS (Auckl) 5: 1–17.
- 137. Fenner L, Brinkhof MW, Keiser O, Weigel R, Cornell M, et al. (2010) Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa. Journal of acquired immune deficiency syndromes (1999) 54: 524.
- 138. Groh K, Audet C, Baptista A, Sidat M, Vergara A, et al. (2011) Barriers to antiretroviral therapy adherence in rural Mozambique. BMC public health 11: 650.
- 139. Audet CM, Groh K, Moon TD, Vermund SH, Sidat M (2012) Poor-quality health services and lack of programme support leads to low uptake of HIV testing in rural Mozambique. African Journal of AIDS Research 11: 327–335.
- 140. Geelhoed D, Lafort Y, Chissale E, Candrinho B, Degomme O (2013) Integrated maternal and child health services in Mozambique: structural health system limitations overshadow its effect on follow-up of HIV-exposed infants. BMC Health Serv Res 13: 207.
- 141. Lambdin BH, Micek MA, Sherr K, Gimbel S, Karagianis M, et al. (2013) Integration of HIV care and treatment in primary health care centers and patient retention in central Mozambique: a retrospective cohort study. J Acquir Immune Defic Syndr 62: e146–152.
- 142. Audet CM, Sidat M, Blevins M, Moon TD, Vergara A, et al. (2012) HIV knowledge and health-seeking behavior in Zambezia Province, Mozambique. SAHARA J 9: 41–46.
- 143. Ciampa PJ, Skinner SL, Patricio SR, Rothman RL, Vermund SH, et al. (2012) Comprehensive knowledge of HIV among women in rural Mozambique: development and validation of the HIV knowledge 27 scale. PLoS One 7: e48676.
- 144. Lehe JD, Sitoe NE, Tobaiwa O, Loquiha O, Quevedo JI, et al. (2012) Evaluating operational specifications of point-of-care diagnostic tests: a standardized scorecard. PLoS One 7: e47459.
- 145. Bandali S (2013) HIV Risk Assessment and Risk Reduction Strategies in the Context of Prevailing Gender Norms in Rural Areas of Cabo Delgado, Mozambique. J Int Assoc Provid AIDS Care 12: 50–54.
- 146. Yao J, Murray AT, Agadjanian V, Hayford SR (2012) Geographic influences on sexual and reproductive health service utilization in rural Mozambique. Appl Geogr 32: 601–607.
- 147. Wandeler G, Keiser O, Pfeiffer K, Pestilli S, Fritz C, et al. (2012) Outcomes of antiretroviral treatment programs in rural Southern Africa. J Acquir Immune Defic Syndr 59: e9–16.
- 148. Cook RE, Ciampa PJ, Sidat M, Blevins M, Burlison J, et al. (2011) Predictors of successful early infant diagnosis of HIV in a rural district hospital in Zambezia, Mozambique. J Acquir Immune Defic Syndr 56: e104–109.
- 149. Noden BH, Gomes A, Ferreira A (2010) Influence of religious affiliation and education on HIV knowledge and HIV-related sexual behaviors among unmarried youth in rural central Mozambique. AIDS Care 22: 1285–1294.
- 150. Posse M, Baltussen R (2009) Barriers to access to antiretroviral treatment in Mozambique, as perceived by patients and health workers in urban and rural settings. AIDS Patient Care STDS 23: 867–875.
- 151. Agadjanian V, Sen S (2007) Promises and challenges of faith-based AIDS care and support in Mozambique. Am J Public Health 97: 362–366.
- 152. Vuylsteke B, Bastos R, Barreto J, Crucitti T, Folgosa E, et al. (1993) High prevalence of sexually transmitted diseases in a rural area in Mozambique. Genitourin Med 69: 427–430.
- 153. Vermund SH, Sidat M, Weil LF, Tique JA, Moon TD, et al. (2012) Transitioning HIV care and treatment programs in southern Africa to full local management. AIDS 26: 1303–1310.
- 154. Gormley W, McCaffery J, Quain EE (2011) Moving forward on human resources for health: next steps for scaling up toward universal access to HIV/AIDS prevention, treatment, and care. J Acquir Immune Defic Syndr 57 Suppl 2: S113–115.
- 155. Lambdin BH, Micek MA, Koepsell TD, Hughes JP, Sherr K, et al. (2011) Patient volume, human resource levels, and attrition from HIV treatment programs in central Mozambique. J Acquir Immune Defic Syndr 57: e33–39.
- 156. Fulton BD, Scheffler RM, Sparkes SP, Auh EY, Vujicic M, et al. (2011) Health workforce skill mix and task shifting in low income countries: a review of recent evidence. Hum Resour Health 9: 1.
- 157.
Adjorlolo-Johnson G, Wahl A, Ramachandran S, Strasser S, Kouakou J, et al.. (2012) Scaling up Pediatric HIV Care and Treatment in Africa: Clinical Site Characteristics Associated with Favorable Service Utilization. J Acquir Immune Defic Syndr.
- 158.
Audet CM, Blevins M, Moon TD, Shepherd BE, Vergara A, et al.. (2012) Knowledge and Treatment of HIV/AIDS by traditional healers in central Mozambique. J Altern Comlement Med [In Press].
- 159.
Audet CM, Blevins M, Moon TD, Sidat M, Shepherd BE, et al.. (2012) Traditional healers in rural Mozambique: Qualitative survey of HIV/AIDS-related attitudes and practices. Journal of Social Aspects of HIV/AIDS [In Press].
- 160. Agadjanian V, Menjivar C (2011) Fighting down the scourge, building up the church: organisational constraints in religious involvement with HIV/AIDS in Mozambique. Glob Public Health 6 Suppl 2: S148–162.
- 161.
MEPI (Medical Education Partnership Initiative) (2010)Medical Education Partnership Initiative.
- 162.
The Africa Capacity Building Initiative (1991) The Africa Capacity Building Initiative.
- 163.
CONSAMS (Consortium of New Southern African Medical Schools) (2011) Consortium of New Southern African Medical Schools.
- 164.
Eichbaum Q, Nyarango P, Bowa K, Odonkor P, Ferrao J, et al.. (2012) “Global networks, alliances and consortia” in global health education - The case for south-to-south partnerships. J Acquir Immune Defic Syndr.
- 165. Chen C, Buch E, Wassermann T, Frehywot S, Mullan F, et al. (2012) A survey of Sub-Saharan African medical schools. Hum Resour Health 10: 4.
- 166. Mullan F, Frehywot S, Omaswa F, Sewankambo N, Talib Z, et al. (2012) The Medical Education Partnership Initiative: PEPFAR’s effort to boost health worker education to strengthen health systems. Health Aff (Millwood) 31: 1561–1572.
- 167. Mullan F, Frehywot S, Omaswa F, Buch E, Chen C, et al. (2011) Medical schools in sub-Saharan Africa. Lancet 377: 1113–1121.
- 168. Decroo T, Telfer B, Biot M, Maikere J, Dezembro S, et al. (2011) Distribution of antiretroviral treatment through self-forming groups of patients in Tete Province, Mozambique. J Acquir Immune Defic Syndr 56: e39–44.
- 169. Decroo T, Panunzi I, das Dores C, Maldonado F, Biot M, et al. (2009) Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique. J Int AIDS Soc 12: 6.
- 170. Decroo T, Van Damme W, Kegels G, Remartinez D, Rasschaert F (2012) Are Expert Patients an Untapped Resource for ART Provision in Sub-Saharan Africa? AIDS Res Treat 2012: 749718.
- 171.
Bandali S (2012) HIV Risk Assessment and Risk Reduction Strategies in the Context of Prevailing Gender Norms in Rural Areas of Cabo Delgado, Mozambique. J Int Assoc Physicians AIDS Care (Chic).
- 172. Bandali S (2011) Norms and practices within marriage which shape gender roles, HIV/AIDS risk and risk reduction strategies in Cabo Delgado, Mozambique. AIDS Care 23: 1171–1176.
- 173. Lahuerta M, Lima J, Nuwagaba-Biribonwoha H, Okamura M, Alvim MF, et al. (2012) Factors associated with late antiretroviral therapy initiation among adults in Mozambique. PLoS One 7: e37125.
- 174. Hendriksen IC, Ferro J, Montoya P, Chhaganlal KD, Seni A, et al. (2012) Diagnosis, Clinical Presentation, and In-Hospital Mortality of Severe Malaria in HIV-Coinfected Children and Adults in Mozambique. Clin Infect Dis 55: 1144–1153.
- 175. Naniche D, Letang E, Nhampossa T, David C, Menendez C, et al. (2011) Alterations in T cell subsets in human immunodeficiency virus-infected adults with co-infections in southern Mozambique. Am J Trop Med Hyg 85: 776–781.
- 176. Modjarrad K, Vermund SH (2010) Effect of treating co-infections on HIV-1 viral load: a systematic review. Lancet Infect Dis 10: 455–463.
- 177. Modjarrad K, Vermund SH (2011) An addition to the effect of treating co-infections on HIV-1 viral load. Lancet Infect Dis 11: 81.
- 178. Vaz P, Augusto O, Bila D, Macassa E, Vubil A, et al. (2012) Surveillance of HIV drug resistance in children receiving antiretroviral therapy: a pilot study of the World Health Organization’s generic protocol in Maputo, Mozambique. Clin Infect Dis 54 Suppl 4: S369–374.
- 179. Holmes CB, Blandford JM, Sangrujee N, Stewart SR, DuBois A, et al. (2012) PEPFAR’s past and future efforts to cut costs, improve efficiency, and increase the impact of global HIV programs. Health Aff (Millwood) 31: 1553–1560.
- 180. Jani IV, Sabatier J, Vubil A, Subbarao S, Bila D, et al. (2012) Evaluation of a high-throughput diagnostic system for detection of HIV-1 in dried blood spot samples from infants in Mozambique. J Clin Microbiol 50: 1458–1460.
- 181. Jani IV, Sitoe NE, Alfai ER, Chongo PL, Quevedo JI, et al. (2011) Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet 378: 1572–1579.
- 182. Bwakura-Dangarembizi M, Kendall L, Bakeera-Kitaka S, Nahirya-Ntege P, Keishanyu R, et al. (2014) A Randomized Trial of Prolonged Co-trimoxazole in HIV-Infected Children in Africa. New England Journal of Medicine 370: 41–53.