Correction: What gaps remain in the HIV cascade of care? Results of a population-based survey in Nsanje District, Malawi.

[This corrects the article DOI: 10.1371/journal.pone.0248410.].

Adolescents and young adults are the most undiagnosed of HIV and virally unsuppressed in Eastern and Southern Africa: Pooled analyses from five population-based surveys.

Age and gender disparities within the HIV cascade of care are critical to focus interventions efficiently. We assessed gender-age groups at the highest probability of unfavorable outcomes in the HIV cascade in five HIV prevalent settings. We performed pooled data analyses from population-based surveys conducted in Kenya, South Africa, Malawi and Zimbabwe between 2012 and 2016. Individuals aged 15-59 years were eligible. Participants were tested for HIV and viral load was measured. The HIV cascade outcomes and the probability of being undiagnosed, untreated among those diagnosed, and virally unsuppressed (≥1,000 copies/mL) among those treated were assessed for several age-gender groups. Among 26,743 participants, 5,221 (19.5%) were HIV-positive (69.9% women, median age 36 years). Of them, 72.8% were previously diagnosed and 56.7% virally suppressed (88.5% among those treated). Among individuals 15-24 years, 51.5% were diagnosed vs 83.0% among 45-59 years, p<0.001. Among 15-24 years diagnosed, 60.6% were treated vs 86.5% among 45-59 years, p<0.001. Among 15-24 years treated, 77.9% were virally suppressed vs 92.0% among 45-59 years, p<0.001. Among all HIV-positive, viral suppression was 32.9% in 15-24 years, 47.9% in 25-34 years, 64.9% in 35-44 years, 70.6% in 45-59 years. Men were less diagnosed than women (65.2% vs 76.0%, p <0.001). Treatment among diagnosed and viral suppression among treated was not different by gender. Compared to women 45-59 years, young people had a higher probability of being undiagnosed (men 15-24 years OR: 37.9, women 15-24 years OR: 12.2), untreated (men 15-24 years OR:2.2, women 15-24 years OR: 5.7) and virally unsuppressed (men 15-24 years OR: 1.6, women 15-24 years OR: 6.6). In these five Eastern and Southern Africa settings, adolescents and young adults had the largest gaps in the HIV cascade. They were less diagnosed, treated, and virally suppressed, than older counterparts. Targeted preventive, testing and treating interventions should be scaled-up.

Effectiveness of typhoid conjugate vaccine in Zimbabwe used in response to an outbreak among children and young adults: A matched case control study.

BACKGROUND: Zimbabwe suffers from regular outbreaks of typhoid fever (TF), worse since 2017. Most cases were in Harare and a vaccination campaign with Typhoid Conjugate Vaccine (TCV) was conducted in March 2019. The vaccine effectiveness (VE) was assessed against culture-confirmed S. Typhi in children six months to 15 years and in individuals six months to 45 years in Harare. METHODS: A matched case-control study was conducted in three urban suburbs of Harare targeted by the TCV vaccination campaign. Suspected TF cases were enrolled prospectively in four health facilities and were matched to facility (1:1) and community (1:5) controls. FINDINGS: Of 504 suspected cases from July 2019 to March 2020, 148 laboratory-confirmed TF cases and 153 controls confirmed-negative were identified. One hundred and five (47 aged six months to 15 years) cases were age, sex, and residence matched with 105 facility-based controls while 96 cases were matched 1:5 by age, sex, and immediate-neighbour with 229 community controls. The adjusted VE against confirmed TF was 75% (95%CI: 1-94, p = 0.049) compared to facility controls, and 84% (95%CI: 57-94, p < 0.001) compared to community controls in individuals six months to 15 years. The adjusted VE against confirmed TF was 46% (95%CI: 26-77, p = 0.153) compared to facility controls, and 67% (95%CI: 35-83, p = 0.002) compared to community controls six months to 45 years old. INTERPRETATION: This study confirms that one vaccine dose of TCV is effective to control TF in children between six months and 15 years old in an African setting.

Human Mobility and Health: Exploring the Health Conditions of Venezuelan Migrants and Refugees in Colombia.

Médecins sans Frontières (MSF) conducted a study to identify health needs and access barriers of Venezuelan migrants and refugees at La Guajira and Norte de Santander Colombian border states. The Migration History tool was used to gather information that included various health-related issues such as referred morbidity, exposure to violence, mental health, and access to health care services. A group migration profile with long-term permanence plans was identified. Was evidenced an important share of young population (50% under 20), indigenous people (20%), and returnees (11%). The respondents referred to a mixed pattern of chronic and acute diseases, for which the main difficulty was accessing diagnosis and continuous treatment. Health-seeking behavior was identified as the main barrier to access health care services. The article compiles main findings on the Venezuelan migrants and refugees' health conditions, contributing important evidence for the humanitarian responses in migration contexts.

What gaps remain in the HIV cascade of care? Results of a population-based survey in Nsanje District, Malawi.

INTRODUCTION: The Malawi Ministry of Health (MoH) has been in collaboration with Médecins sans Frontières (MSF) to increase access to quality HIV care through decentralization of antiretroviral therapy (ART) diagnosis and treatment from hospital to clinics in Nsanje District since 2011. A population-based household survey was implemented to provide information on HIV prevalence and cascade of care to inform and prioritize community-based HIV interventions in the district. METHODS: A cross-sectional survey was conducted between September 2016 and January 2017. Using two-stage cluster sampling, eligible adult individuals aged ≥15 years living in the selected households were asked to participate. Participants were interviewed and tested for HIV at home. Those tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their ART status. All participants tested HIV-positive at the time of the survey were advised to report their HIV test result to the health facility of their choice that MSF was supported in the district. HIV-RNA VL results were made available in this health facility. RESULTS: Among 5,315 eligible individuals, 91.1% were included in the survey and accepted an HIV test. The overall prevalence was 12.1% (95% Confidence Interval (CI): 11.2-13.0) and was higher in women than in men: 14.0% versus 9.5%, P<0.001. Overall HIV-positive status awareness was 80.0% (95%CI: 76.4-83.1) and was associated with sex (P<0.05). Linkage to care was 78.0% (95%CI: 74.3-81.2) and participants in care 76.2% (95%CI: 72.4-79.5). ART coverage among participants aware of their HIV-positive status was 95.3% (95%CI: 92.9-96.9) and was not associated with sex (P = 0.55). Viral load suppression among participants on ART was 89.9% (95%CI: 86.6-92.4) and was not statistically different by sex (p = 0.40). CONCLUSIONS: Despite encouraging results in HIV testing coverage, cascade of care, and UNAIDS targets in Nsanje District, some gap remains in the first 90, specifically among men and young adults. Enhanced community engagement and new strategies of testing, such as index testing, could be implemented to identify those who are still undiagnosed, particularly men and young adults.

Successes and gaps in the HIV cascade of care of a high HIV prevalence setting in Zimbabwe: a population-based survey.

INTRODUCTION: Gutu, a rural district in Zimbabwe, has been implementing comprehensive HIV care with the support of Médecins Sans Frontières (MSF) since 2011, decentralizing testing and treatment services to all rural healthcare facilities. We evaluated HIV prevalence, incidence and the cascade of care, in Gutu District five years after MSF began its activities. METHODS: A cross-sectional study was implemented between September and December 2016. Using multistage cluster sampling, individuals aged ≥15 years living in the selected households were eligible. Individuals who agreed to participate were interviewed and tested for HIV at home. All participants who tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their antiretroviral therapy (ART) status, and those not on ART with HIV-RNA VL ≥ 1000 copies/mL had Limiting-Antigen-Avidity EIA Assay for cross-sectional estimation of population-level HIV incidence. RESULTS: Among 5439 eligible adults ≥15 years old, 89.0% of adults were included in the study and accepted an HIV test. The overall prevalence was 13.6% (95%: Confidence Interval (CI): 12.6 to 14.5). Overall HIV-positive status awareness was 87.4% (95% CI: 84.7 to 89.8), linkage to care 85.5% (95% CI: 82.5 to 88.0) and participants in care 83.8% (95% CI: 80.7 to 86.4). ART coverage among HIV-positive participants was 83.0% (95% CI: 80.0 to 85.7). Overall, 71.6% (95% CI 68.0 to 75.0) of HIV-infected participants had a HIV-RNA VL < 1000 copies/mL. Women achieved higher outcomes than men in the five stages of the cascade of care. Viral Load Suppression (VLS) among participants on ART was 83.2% (95% CI: 79.7 to 86.2) and was not statistically different between women and men (p = 0.98). The overall HIV incidence was estimated at 0.35% (95% CI 0.00 to 0.70) equivalent to 35 new cases/10,000 person-years. CONCLUSIONS: Our study provides population-level evidence that achievement of HIV cascade of care coverage overall and among women is feasible in a context with broad access to services and implementation of a decentralized model of care. However, the VLS was relatively low even among participants on ART. Quality care remains the most critical gap in the cascade of care to further reduce mortality and HIV transmission.

Setting up a nurse-led model of care for management of hypertension and diabetes mellitus in a high HIV prevalence context in rural Zimbabwe: a descriptive study.

BACKGROUND: In the light of the increasing burden of non-communicable diseases (NCDs) on health systems in low- and middle-income countries, particularly in Sub-Saharan Africa, context-adapted, cost-effective service delivery models are now required as a matter of urgency. We describe the experience of setting up and organising a nurse-led Diabetes Mellitus (DM) and Hypertension (HTN) model of care in rural Zimbabwe, a low-income country with unique socio-economic challenges and a dual disease burden of HIV and NCDs. METHODS: Mirroring the HIV experience, we designed a conceptual framework with 9 key enablers: decentralization of services, integration of care, simplification of management guidelines, mentoring and task-sharing, provision of affordable medicines, quality assured laboratory support, patient empowerment, a dedicated monitoring and evaluation system, and a robust referral system. We selected 9 primary health care clinics (PHC) and two hospitals in Chipinge district and integrated DM and HTN either into the general out-patient department, pre-existing HIV clinics, or an integrated chronic care clinic (ICCC). We provided structured intensive mentoring for staff, using simplified protocols, and disease-specific education for patients. Free medication with differentiated periodic refills and regular monitoring with point of care (POC) glycosylated haemoglobin (HbA1c) were provided. RESULTS: Nurses in 7 PHC facilities and one hospital developed sufficient knowledge and skills to diagnose, initiate treatment and monitor DM and HTN patients, and 3094 patients were registered in the programme (188 with DM only, 2473 with HTN only, 433 with both DM and HTN). Major lessons learned from our experience include: the value of POC devices in the management of diabetes; the pressure on services of the added caseload, exacerbated by the availability of free medications in supported health facilities; and the importance of leadership in the successful implementation of care in health facilities. CONCLUSION: Our experience demonstrates a model for nurse-led decentralized integrated DM and HTN care in a high HIV prevalence rural, low-income context. Developing a context-adapted efficient model of care is a dynamic process. We present our lessons learned with the intention of sharing experience which may be of value to other public health programme managers.

Patient and health-care worker experiences of an HIV viral load intervention using SMS: A qualitative study.

BACKGROUND: Mobile Health or mHealth interventions, including Short Message Service (SMS), can help increase access to care, enhance the efficiency of health service delivery and improve diagnosis and treatment for HIV. Text messaging, or SMS, allows for the low cost transmission of information, and has been used to send appointment reminders, information about HIV counselling and treatment, messages to encourage adherence and information on nutrition and side-effects. HIV Viral Load (VL) monitoring is recommended by the WHO and has been progressively adopted in many settings. In Zimbabwe, implementation of VL is routine and has been rolled out with support of Médecins Sans Frontières (MSF) since 2012. An SMS intervention to assist with the management of VL results was introduced in two rural districts of Zimbabwe. After completion of the HIV VL testing at the National Microbiology Reference Laboratory in Harare, results were sent to health facilities via SMS. Consenting patients were also sent an SMS informing them that their viral load results were ready for collection at their nearest health facilities. No actual VL results were sent to patients. METHODS: A qualitative study was conducted in seven health-care facilities using in-depth interviews (n = 32) and focus group discussions (n = 5) to explore patient and health-care worker experiences of the SMS intervention. Purposive sampling was used to select participants to ensure that male and female patients, as well as those with differing VL results and who lived differing distances from the clinics were included. Data were transcribed, translated from Shona into English, coded and thematically analysed using NVivo software. RESULTS: The VL SMS intervention was considered acceptable to patients and health-care workers despite some challenges in implementation. The intervention was perceived by health-care workers as improving adherence and well-being of patients as well as improving the management of VL results at health facilities. However, there were some concerns from participants about the intervention, including challenges in understanding the purpose and language of the messages and patients coming to their health facility unnecessarily. Health-care workers were more concerned than patients about unintentional HIV disclosure relating to the content of the messages or phone-sharing. CONCLUSION: This was an innovative intervention in Zimbabwe, in which SMS was used to send VL results to health-care facilities, and notifications of the availability of VL results to patients. Interventions such as this have the potential to reduce unnecessary clinic visits and ensure patients with high VL results receive timely support, but they need to be properly explained, alongside routine counselling, for patients to fully benefit. The findings of this study also have potential policy implications, as if implemented well, such an SMS intervention has the potential to help patients adopt a more active role in the self-management of their HIV disease, become more aware of the importance of adherence and VL monitoring and seek follow-up at clinics when results are high.

Multidisease testing for HIV and TB using the GeneXpert platform: A feasibility study in rural Zimbabwe.

BACKGROUND: HIV Viral Load and Early Infant Diagnosis technologies in many high burden settings are restricted to centralized laboratory testing, leading to long result turnaround times and patient attrition. GeneXpert (Cepheid, CA, USA) is a polyvalent near point-of-care platform and is widely implemented for Xpert MTB/RIF diagnosis. This study sought to evaluate the operational feasibility of integrated HIV VL, EID and MTB/RIF testing in new GeneXpert platforms. METHODS: Whole blood samples were collected from consenting patients due for routine HIV VL testing and DBS samples from infants due for EID testing, at three rural health facilities in Zimbabwe. Sputum samples were collected from all individuals suspected of TB. GeneXpert testing was reserved for all EID, all TB suspects and priority HIV VL at each site. Blood samples were further sent to centralized laboratories for confirmatory testing. GeneXpert polyvalent testing results and patient outcomes, including infrastructural and logistical requirements are reported. The study was conducted over a 10-month period. RESULTS: The fully automated GeneXpert testing device, required minimal training and biosafety considerations. A total of 1,302 HIV VL, 277 EID and 1,581 MTB/RIF samples were tested on a four module GeneXpert platform in each study site. Xpert HIV-1 VL testing was prioritized for patients who presented with advanced HIV disease, pregnant women, adolescents and suspected ART failures patients. On average, the study sites had a GeneXpert utilization rate of 50.4% (Gutu Mission Hospital), 63.5% (Murambinda Mission Hospital) and 17.5% (Chimombe Rural Health Centre) per month. GeneXpert polyvalent testing error rates remained lower than 4% in all sites. Decentralized EID and VL testing on Xpert had shorter overall median TAT (1 day [IQR: 0-4] and 1 day [IQR: 0-1] respectively) compared to centralized testing (17 days [IQR: 13-21] and 26 days [IQR: 23-32] respectively). Among patients with VL >1000 copies/ml (73/640; 11.4%) at GMH health facility, median time to enhanced adherence counselling was 8 days and majority of those with documented outcomes had re-suppressed VL (20/32; 62.5%). Median time to ART initiation among Xpert EID positive infants at GMH was 1 day [IQR: 0-1]. CONCLUSION: Implementation of near point-of-care GeneXpert platform for integrated multi-disease testing within district and sub-district healthcare settings is feasible and will increase access to VL, and EID testing to priority populations. Quality management systems including monitoring of performance indicators, together with regular on-site supervision are crucial, and near-POC test results must be promptly actioned-on by clinicians for patient management.

Greater retention in care among adolescents on antiretroviral treatment accessing "Teen Club" an adolescent-centred differentiated care model compared with standard of care: a nested case-control study at a tertiary referral hospital in Malawi.

INTRODUCTION: There are numerous barriers to the care and support of adolescents living with HIV (ALHIV) that makes this population particularly vulnerable to attrition from care, poor adherence and virological failure. In 2010, a Teen Club was established in Zomba Central Hospital (ZCH), Malawi, a tertiary referral HIV clinic. Teen Club provides ALHIV on antiretroviral treatment (ART) with dedicated clinic time, sexual and reproductive health education, peer mentorship, ART refill and support for positive living and treatment adherence. The purpose of this study was to evaluate whether attending Teen Club improves retention in ART care. METHODS: We conducted a nested case-control study with stratified selection, using programmatic data from 2004 to 2015. Cases (ALHIV not retained in care) and controls (ALHIV retained in care) were matched by ART initiation age group. Patient records were reviewed retrospectively and subjects were followed starting in March 2010, the month in which Teen Club was opened. Follow-up ended at the time patients were no longer considered retained in care or on 31 December 2015. Cases and controls were drawn from a study population of 617 ALHIV. Of those, 302 (48.9%) participated in at least two Teen Club sessions. From the study population, 135 (non-retained) cases and 405 (retained) controls were selected. RESULTS: In multivariable analyses, Teen Club exposure, age at the time of selection and year of ART initiation were independently associated with attrition. ALHIV with no Teen Club exposure were less likely to be retained than those with Teen Club exposure (adjusted odds ratio (aOR) 0.27; 95% CI 0.16, 0.45) when adjusted for sex, ART initiation age, current age, reason for ART initiation and year of ART initiation. ALHIV in the age group 15 to 19 were more likely to have attrition from care than ALHIV in the age group 10 to 14 years of age (aOR 2.14; 95% CI 1.12, 4.11). CONCLUSIONS: This study contributes to the limited evidence evaluating the effectiveness of service delivery interventions to support ALHIV within healthcare settings. Prospective evaluation of the Teen Club package with higher methodological quality is required for programmes and governments in low- and middle-income settings to prioritize interventions for ALHIV and determine their cost-effectiveness.

The burden of gynecomastia among men on antiretroviral therapy in Zomba, Malawi.

BACKGROUND: Many Africans who are on life-saving ART face challenges from a variety of toxicities. After the introduction of a standardized first-line efavirenz-containing ART regimen, reports of gynecomastia appeared in Malawian popular media, however data on the prevalence and risk factors of gynecomastia from Africa are lacking. METHODS: We conducted a cross-sectional study in males ≥18 years registered on ART at the HIV clinic in Zomba Central Hospital. Men who reported to have ever experienced breast or nipple enlargement received a standard questionnaire and underwent physical examination. Questions included perceptions and concerns about gynecomastia. Clinicians confirmed the presence and severity of gynecomastia. Routinely collected data on current and previous ART regimens, CD4 count, WHO clinical stage, anthropometric measurements and history of tuberculosis were extracted from the electronic database. RESULTS: We enrolled 1,027 men with median age 44 years (IQR: 38-52). The median ART duration was 57 months (IQR: 27-85); 46.7% were in WHO stage III/IV at ART initiation, 88.2% had exposure to efavirenz and 9% were overweight or obese. The prevalence of self-reported gynecomastia was 6.0% (62/1027) (95%-CI: 4.7-7.7%). Of men with gynecomastia 83.6% reported nipple enlargement and 98.4% enlarged breasts (85.5% bilateral). One-third said they had not reported gynecomastia to a health care worker. Over three-quarters mentioned that gynecomastia was an important or very important problem for them, while more than half were embarrassed by it. On examination gynecomastia was present in 90% (confirmed gynecomastia prevalence 5.5%; 95%-CI: 4.2-7.0%) and 51.8% had severity grade III or IV. History of tuberculosis treatment was independently associated with self-reported gynecomastia, adjusted OR 2.10 (95%-CI: 1.04-4.25). CONCLUSIONS: The burden of gynecomastia among men on ART in Malawi was higher than previously reported, and was associated with adverse psychological consequences, calling for increased awareness, a proactive diagnostic approach and diligent clinical management.

Virological outcomes of antiretroviral therapy in Zomba central prison, Malawi; a cross-sectional study.

INTRODUCTION: Antiretroviral therapy (ART) outcomes that include viral suppression rates are rarely reported among African prison populations. Prisoners deal with specific challenges concerning adherence to ART. We aimed to describe virological outcomes of ART in a large prison in Malawi. METHODS: A cross-sectional study of ART outcomes was conducted at the Zomba Central Prison HIV clinic, Malawi, following the introduction of routine viral load monitoring. All prisoners on ART for at least 6 months were eligible for a viral load test. Patients with ≥1,000 copies/ml received adherence support for 3 months, after which a second VL sample was taken. Patients with ≥5,000 copies/ml on the second sample had virological failure and started 2nd line ART. We describe demographics and patient characteristics and report prevalence of potential- and documented virological failure. In the potential virological failure rate, those who could not be sampled after 3 months adherence support are included as virological failures. Logistic regression analysis was used to determine factors associated with potential ART failure. RESULTS AND DISCUSSION: Viral load testing was started at the end of 2014, when 1054 patients had ever registered on ART. Of those, 501 (47.5%) had transferred out to another clinic, 96 (9.1%) had died, 11 defaulted (1.0%) and 3 (0.3%) stopped ART. Of 443 (42.0%) remaining alive in care, an estimated 322 prisoners were on ART >6 months, of whom 262 (81.4%) were sampled. Their median age was 35 years (IQR 31-40) and 257 (98.1%) were male. Self-reported adherence was good in 258 (98.5%). The rate of potential ART failure was 8.0%, documented ART failure was 4.6% and documented HIV suppression 95.0%. No patient characteristics were independently associated with potential ART failure, possibly due to low numbers with this outcome. CONCLUSIONS: Good virological suppression rates can be achieved among Malawian prisoners on ART, under challenging circumstances.

The burden of hypertension, diabetes mellitus, and cardiovascular risk factors among adult Malawians in HIV care: consequences for integrated services.

BACKGROUND: Hypertension and diabetes prevalence is high in Africans. Data from HIV infected populations are limited, especially from Malawi. Integrating care for chronic non-communicable co-morbidities in well-established HIV services may provide benefit for patients by preventing multiple hospital visits but will increase the burden of care for busy HIV clinics. METHODS: Cross-sectional study of adults (≥18 years) at an urban and a rural HIV clinic in Zomba district, Malawi, during 2014. Hypertension and diabetes were diagnosed according to stringent criteria. Proteinuria, non-fasting lipids and cardio/cerebro-vascular disease (CVD) risk scores (Framingham and World Health Organization/International Society for Hypertension) were determined. The association of patient characteristics with diagnoses of hypertension and diabetes was studied using multivariable analyses. We explored the additional burden of care for integrated drug treatment of hypertension and diabetes in HIV clinics. We defined that burden as patients with diabetes and/or stage II and III hypertension, but not with stage I hypertension unless they had proteinuria, previous stroke or high Framingham CVD risk. RESULTS: Nine hundred fifty-two patients were enrolled, 71.7% female, median age 43.0 years, 95.9% on antiretroviral therapy (ART), median duration 47.7 months. Rural and urban patients' characteristics differed substantially. Hypertension prevalence was 23.7% (95%-confidence interval 21.1-26.6; rural 21.0% vs. urban 26.5%; p = 0.047), of whom 59.9% had stage I (mild) hypertension. Diabetes prevalence was 4.1% (95%-confidence interval 3.0-5.6) without significant difference between rural and urban settings. Prevalence of proteinuria, elevated total/high-density lipoprotein-cholesterol ratio and high CVD risk score was low. Hypertension diagnosis was associated with increasing age, higher body mass index, presence of proteinuria, being on regimen zidovudine/lamivudine/nevirapine and inversely with World Health Organization clinical stage at ART initiation. Diabetes diagnosis was associated with higher age and being on non-standard first-line or second-line ART regimens. CONCLUSION: Among patients in HIV care 26.6% had hypertension and/or diabetes. Close to two-thirds of hypertension diagnoses was stage I and of those few had an indication for antihypertensive pharmacotherapy. According to our criteria, 13.0% of HIV patients in care required drug treatment for hypertension and/or diabetes.

Incidence of AIDS-defining and Other Cancers in HIV-positive Children in South Africa: Record Linkage Study.

BACKGROUND: Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa. METHODS: We linked the records of 5 ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria. RESULTS: Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI: 55-122). The most frequent cancers were Kaposi sarcoma (34 per 100,000 person-years) and non-Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR: 0.29; 95% CI: 0.09-0.86), and increased with age at enrollment (>10 vs. <3 years: HR: 7.3; 95% CI: 2.2-24.6) and immunodeficiency at enrollment (advanced/severe versus no/mild: HR: 3.5; 95% CI: 1.1-12.0). The HR for the effect of ART from complete case analysis was similar but ceased to be statistically significant (P = 0.078). CONCLUSIONS: Early HIV diagnosis and linkage to care, with start of ART before advanced immunodeficiency develops, may substantially reduce the burden of cancer in HIV-positive children in South Africa and elsewhere.

Growth in Virologically Suppressed HIV-Positive Children on Antiretroviral Therapy: Individual and Population-level References.

BACKGROUND: Combination antiretroviral therapy (ART) suppresses viral replication in HIV-infected children. The growth of virologically suppressed children on ART has not been well documented. We aimed to develop dynamic reference curves for weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ). METHODS: Children aged <11 years at ART initiation with continuously undetectable viral loads (<400 copies/mL) treated at 7 South African ART programs with routine viral load monitoring were included. We used multilevel models to define trajectories of WAZ and HAZ up to 3 years and developed a web application to monitor trajectories in individual children. RESULTS: A total of 4876 children were followed for 7407 person-years. Analyses were stratified by baseline Z scores and age, which were the most important predictors of growth response. The youngest children showed the most pronounced increase in weight and height initially but catch-up growth stagnated after 1-2 years. Three years after starting ART, WAZ ranged from -2.2 [95% prediction interval (PrI), -5.6 to 0.8] in children with baseline age >5 years and Z score less than -3 to 0.0 (95% PrI, -2.7 to 2.4) in children with baseline age <2 years and WAZ greater than -1. For HAZ, the corresponding range was -2.3 (95% PrI, -4.9 to 0.3) in children with baseline age >5 years and Z score less than -3 to 0.3 (95% PrI, -3.1 to 3.4) in children with baseline age 2-5 years and HAZ greater than -1. CONCLUSIONS: We have developed an online tool to calculate reference trajectories in fully suppressed children. The web application could help to define "optimal" growth response and identify children with treatment failure.

Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral therapy in Southern Africa: a prospective multicohort study.

BACKGROUND: The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. METHODS: We included patient data of 6 ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. FINDINGS: We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. Five hundred and sixty-four incident cases were diagnosed during 343,927 person-years (pys). The overall KS incidence rate was 164/100,000 pys [95% confidence interval (CI): 151 to 178]. The incidence rate was highest 30-90 days after ART initiation (413/100,000 pys; 95% CI: 342 to 497) and declined thereafter [86/100,000 pys (95% CI: 71 to 105), >2 years after ART initiation]. Male sex [adjusted hazard ratio (HR): 1.34; 95% CI: 1.12 to 1.61], low current CD4 counts (≥500 versus <50 cells/µL, adjusted HR: 0.36; 95% CI: 0.23 to 0.55), and age (5-9 years versus 30-39 years, adjusted HR: 0.20; 95% CI: 0.05 to 0.79) were relevant risk factors for developing KS. INTERPRETATION: Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality.

Mortality in patients with HIV-1 infection starting antiretroviral therapy in South Africa, Europe, or North America: a collaborative analysis of prospective studies.

BACKGROUND: High early mortality in patients with HIV-1 starting antiretroviral therapy (ART) in sub-Saharan Africa, compared to Europe and North America, is well documented. Longer-term comparisons between settings have been limited by poor ascertainment of mortality in high burden African settings. This study aimed to compare mortality up to four years on ART between South Africa, Europe, and North America. METHODS AND FINDINGS: Data from four South African cohorts in which patients lost to follow-up (LTF) could be linked to the national population register to determine vital status were combined with data from Europe and North America. Cumulative mortality, crude and adjusted (for characteristics at ART initiation) mortality rate ratios (relative to South Africa), and predicted mortality rates were described by region at 0-3, 3-6, 6-12, 12-24, and 24-48 months on ART for the period 2001-2010. Of the adults included (30,467 [South Africa], 29,727 [Europe], and 7,160 [North America]), 20,306 (67%), 9,961 (34%), and 824 (12%) were women. Patients began treatment with markedly more advanced disease in South Africa (median CD4 count 102, 213, and 172 cells/µl in South Africa, Europe, and North America, respectively). High early mortality after starting ART in South Africa occurred mainly in patients starting ART with CD4 count <50 cells/µl. Cumulative mortality at 4 years was 16.6%, 4.7%, and 15.3% in South Africa, Europe, and North America, respectively. Mortality was initially much lower in Europe and North America than South Africa, but the differences were reduced or reversed (North America) at longer durations on ART (adjusted rate ratios 0.46, 95% CI 0.37-0.58, and 1.62, 95% CI 1.27-2.05 between 24 and 48 months on ART comparing Europe and North America to South Africa). While bias due to under-ascertainment of mortality was minimised through death registry linkage, residual bias could still be present due to differing approaches to and frequency of linkage. CONCLUSIONS: After accounting for under-ascertainment of mortality, with increasing duration on ART, the mortality rate on HIV treatment in South Africa declines to levels comparable to or below those described in participating North American cohorts, while substantially narrowing the differential with the European cohorts. Please see later in the article for the Editors' Summary.

Mortality among adults transferred and lost to follow-up from antiretroviral therapy programmes in South Africa: a multicenter cohort study.

BACKGROUND AND OBJECTIVES: Little is known about outcomes after transfer out (TFO) and loss to follow-up (LTF) and how differential outcomes might bias mortality estimates, as analyses generally censor or exclude TFOs/LTF. Using data linked to the National Population Register, we explored mortality among TFO and LTF patients compared with patients who were retained and investigated how linkage impacted on mortality estimates. METHODS: A cohort analysis of routine data on adults with civil identification numbers starting antiretroviral therapy (ART) 2004-2009 in 4 large South African ART cohorts. The number, proportion, timing, and mortality of TFOs and LTF were reported. Mortality was compared using Kaplan-Meier curves, Cox's proportional hazards, and competing risks regression. RESULTS: Before linkage, 1207 patients (6%) had died, 2624 (13%) were LTF, 1067 (5%) were TFO and 14,583 (75%) were retained. Compared with retained, mortality risk was 3 times higher among TFO patients [adjusted hazard ratio (aHR), 3.11; 95% confidence interval (CI): 2.42 to 3.99] and 20 times higher among LTF patients (aHR, 22.03; 95% CI: 20.05 to 24.21). Excluding early deaths after TFO or LTF, the risk was comparable among TFOs and retained (aHR, 0.75; 95% CI: 0.54 to 1.03) and higher among LTF (aHR, 2.85; 95% CI: 2.43 to 3.33). After linkage, corrected mortality was higher than site-reported mortality. Censoring did not, however, lead to substantial underestimation of mortality among TFOs. CONCLUSIONS: Although TFO and LTF predicted mortality, the lower incidence of TFO and subsequent death compared with LTF meant that censoring TFOs did not bias mortality estimates. Future cohort analyses should explicitly consider proportions of TFO/LTF and mortality event rates.