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Few national programs and research cohorts within low- and middle-income countries (LMICs) document transition-related processes and outcomes for adolescents and young adults living with HIV (AYLH) transitioning to adulthood. Between 2017-2020, The Global fRAmework of Data collection Used for Adolescent HIV Transition Evaluation (GRADUATE) project convened a collaborative advisory group to identify key variables and definitions capturing the process, predictors, and outcomes across the transition period. In total, 114 variables identified as essential to measuring AYLH transition-related data were identified and formatted into a GRADUATE Data Exchange Standard (DES), which was added to and harmonized with the existing International epidemiology Databases to Evaluate AIDS (IeDEA) DES. In 2019, the GRADUATE DES was pilot tested at four IeDEA facilities in Malawi, South Africa, and Thailand through a cross-sectional study. Upon comparing the variables to routine medical records, available data were too limited to adequately capture transition-related processes and outcomes. However, additional data collection using GRADUATE tools was feasible and improved completeness. Of the 100 (52% female) AYLH included in the pilot study, 71% had transitioned/transferred to adult care, with 42% transitioning from an adolescent-specific model of care within an integrated family clinic to having their clinic visits scheduled on a different day of the week while 58% transferred from a pediatric facility to one offering adult HIV care. While almost all (94%) had a transition-related discussion with their healthcare providers prior to the transition, we found that 69% (95% CI 49-85%) were somewhat or very satisfied/comfortable with the post-transfer clinic and the staff. Utilization of the GRADUATE DES better characterized AYLH transitioning to adulthood across LMICs, and optimally measured transition preparation activities and outcomes. Utilization of the GRADUATE DES in other settings could facilitate comparisons and identify gaps in the care of transitioning adolescents that need to be addressed.
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INTRODUCTION: To eliminate cervical cancer (CC), access to and quality of prevention and care services must be monitored, particularly for women living with HIV (WLHIV). We assessed implementation practices in HIV clinics across sub-Saharan Africa (SSA) to identify gaps in the care cascade and used aggregated patient data to populate cascades for WLHIV attending HIV clinics. METHODS: Our facility-based survey was administered between November 2020 and July 2021 in 30 HIV clinics across SSA that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We performed a qualitative site-level assessment of CC prevention and care services and analysed data from routine care of WLHIV in SSA. RESULTS: Human papillomavirus (HPV) vaccination was offered in 33% of sites. Referral for CC diagnosis (42%) and treatment (70%) was common, but not free at about 50% of sites. Most sites had electronic health information systems (90%), but data to inform indicators to monitor global targets for CC elimination in WLHIV were not routinely collected in these sites. Data were collected routinely in only 36% of sites that offered HPV vaccination, 33% of sites that offered cervical screening and 20% of sites that offered pre-cancer and CC treatment. CONCLUSIONS: Though CC prevention and care services have long been available in some HIV clinics across SSA, patient and programme monitoring need to be improved. Countries should consider leveraging their existing health information systems and use monitoring tools provided by the World Health Organization to improve CC prevention programmes and access, and to track their progress towards the goal of eliminating CC.
Subject(s)
HIV Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Humans , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/diagnosis , Female , Africa South of the Sahara/epidemiology , HIV Infections/prevention & control , HIV Infections/epidemiology , Adult , Papillomavirus Vaccines/administration & dosage , Papillomavirus Infections/prevention & control , Middle Aged , Young Adult , Surveys and Questionnaires , Health Services AccessibilityABSTRACT
Background: The use of big data and large language models in healthcare can play a key role in improving patient treatment and healthcare management, especially when applied to large-scale administrative data. A major challenge to achieving this is ensuring that patient confidentiality and personal information is protected. One way to overcome this is by augmenting clinical data with administrative laboratory dataset linkages in order to avoid the use of demographic information. Methods: We explored an alternative method to examine patient files from a large administrative dataset in South Africa (the National Health Laboratory Services, or NHLS), by linking external data to the NHLS database using specimen barcodes associated with laboratory tests. This offers us with a deterministic way of performing data linkages without accessing demographic information. In this paper, we quantify the performance metrics of this approach. Results: The linkage of the large NHLS data to external hospital data using specimen barcodes achieved a 95% success. Out of the 1200 records in the validation sample, 87% were exact matches and 9% were matches with typographic correction. The remaining 5% were either complete mismatches or were due to duplicates in the administrative data. Conclusions: The high success rate indicates the reliability of using barcodes for linking data without demographic identifiers. Specimen barcodes are an effective tool for deterministic linking in health data, and may provide a method of creating large, linked data sets without compromising patient confidentiality.
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In a large, multi-regional cohort of African infants with HIV exposure, 44% of those with a positive HIV PCR lacked a confirmatory positive test. Efforts are needed to ensure high-fidelity implementation of HIV testing algorithms, so that all positive results are confirmed thereby reducing the risk of potentially false-positive results.
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BACKGROUND: The International epidemiology Databases to Evaluate AIDS conducts research in several regions, including in Southern Africa. We assessed authorship inequalities for the Southern African region, which is led by South African and Swiss investigators. METHODS: We analysed authorships of publications from 2007 to 2020 by gender, country income group, time and citation impact. We used 2020 World Bank categories to define income groups and the relative citation ratio (RCR) to assess citation impact. Authorship parasitism was defined as articles without authors from the countries where the study was conducted. A regression model examined the probability of different authorship positions. RESULTS: We included 313 articles. Of the 1064 contributing authors, 547 (51.4%) were women, and 223 (21.0%) were from 32 low-income/lower middle-income countries (LLMICs), 269 (25.3%) were from 13 upper middle-income countries and 572 (53.8%) were from 25 high-income countries (HICs). Most articles (150/157, 95.5%) reporting data from Southern Africa included authors from all participating countries. Women were more likely to be the first author than men (OR 1.74; 95% CI 1.06 to 2.83) but less likely to be last authors (OR 0.63; 95% CI 0.40 to 0.99). Compared with HIC, LLMIC authors were less likely to publish as first (OR 0.21; 95% CI 0.11 to 0.41) or last author (OR 0.20; 95% CI 0.09 to 0.42). The proportion of women and LLMIC first and last authors increased over time. The RCR tended to be higher, indicating greater impact, if first or last authors were from HIC (p=0.06). CONCLUSIONS: This analysis of a global health collaboration co-led by South African and Swiss investigators showed little evidence of authorship parasitism. There were stark inequalities in authorship position, with women occupying more first and men more last author positions and researchers from LLMIC being 'stuck in the middle' on the byline. Global health research collaborations should monitor, analyse and address authorship inequalities.
Subject(s)
Authorship , Global Health , Male , Humans , Female , Publishing , Income , Africa, SouthernABSTRACT
The risk of HIV acquisition is higher during pregnancy and postpartum than other times. Newly acquired maternal HIV infection associated with high primary viraemia, substantially increases the risk of vertical HIV transmission. Pre-exposure prophylaxis (PrEP) reduces the risk of HIV acquisition. Currently available products include oral tenofovir/emtricitabine (TDF/FTC) and tenofovir alafenamide (TAF)/FTC), long-acting cabotegravir (CAB-LA) and the dapivirine ring (DVR). All except oral TDF/FTC have limited safety data available for use in pregnant and breastfeeding women. The safety of new PrEP agents for pregnant women and the fetus, infant and child, either exposed in utero or during breastfeeding is an ongoing concern for health care workers and pregnant and breastfeeding women, particularly as the safety risk appetite for antiretroviral (ARV) agents used as PrEP is lower in pregnant and breastfeeding women who are HIV-uninfected, compared to women living with HIV taking ARVs as treatment. With the widespread rollout of TDF/FTC among pregnant women in South Africa and other low-middle income countries (LMIC) and the potential introduction of new PrEP agents for pregnant women, there is a need for safety surveillance systems to identify potential signals of risk to either the mother or fetus, measure the burden of such a risk, and where appropriate, provide specific reassurance to PrEP users. Safety data needs to be collected across the continuum of the product life cycle from pre-licensure into the post-marketing period, building a safety profile through both passive and active surveillance systems, recognising the strengths and limitations of each, and the potential for bias and confounding. Pharmacovigilance systems that aim to assess the risk of adverse birth outcomes in pregnant women exposed to PrEP and other agents need to consider the special requirements of pregnancy epidemiology to ensure that the data derived from surveillance are sufficiently robust to inform treatment policies. Here we review the known safety profiles of currently available PrEP candidates in women of child-bearing potential, pregnancy and breastfeeding and discuss pragmatic approaches for such surveillance in HIV-endemic LMICs.
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BACKGROUND: WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited. METHODS: We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg. RESULTS: Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23-71), CD4 percentage was 27.9 (19.2-38.0), and weight was 4.0 kg (3.0-4.7) at ART initiation. In those with ≥1 month's follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5-39.5). Abacavir discontinuations did not differ by age or weight category (p = 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10-0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (p = 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (p = 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.2). CONCLUSION: Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg.
Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Child , Infant, Newborn , Infant , Humans , Zidovudine/adverse effects , Anti-HIV Agents/adverse effects , HIV Infections/drug therapy , Lamivudine/therapeutic use , South Africa/epidemiology , Dideoxynucleosides/adverse effects , Anti-Retroviral Agents/therapeutic use , Viral LoadABSTRACT
BACKGROUND: Among children in Southern Africa severe immune suppression (SIS) has declined, but most continue to initiate antiretroviral therapy (ART) with SIS. SETTING: Using data from South Africa, we describe SIS at ART start and on ART between 2007 and 2020, among children <5 years with a CD4%/cell count at ART start and ≥1 subsequent measure. METHODS: Gap in care was defined as >9 months without a recorded visit. We defined SIS according to age and CD4%/cell count. A multistate model was used to estimate transition probabilities between 5 states: SIS on ART; Stable, not SIS; Early Gap, commencing <9 months from ART start; Late Gap, commencing ≥9 months on ART; and Death. RESULTS: Among 2536 children, 70% had SIS at ART start, and 36% experienced SIS on ART. An increasing proportion were age <1 year at ART initiation (2007-2009: 43% to 2013-2020: 55%). Increasingly, SIS on ART occurred after a gap, in those with SIS on ART for >1 year, and after a period of unknown immune status. Later year of ART initiation was associated with reduced transition from SIS on ART to Stable. Infants and those initiating ART with SIS were more likely to transition from Stable to SIS. Viremia strongly predicted death from both the on ART states. CONCLUSIONS: Increasingly SIS occurred among ART-experienced children. Those starting ART with SIS and during infancy remained especially vulnerable to SIS once on treatment. Managing ART in these children may be more complex and further reducing AIDS-related mortality is likely to remain challenging.
Subject(s)
Anti-HIV Agents , HIV Infections , Infant , Humans , Child , HIV Infections/drug therapy , South Africa/epidemiology , Anti-HIV Agents/therapeutic use , Prevalence , Africa, Southern , CD4 Lymphocyte CountABSTRACT
BACKGROUND: Fixed-dose combination of dolutegravir (DTG) with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC) likely improves adherence and has a favorable resistance profile. We evaluated predicted efficacy of TLD (TDF-3TC-DTG) in children and adolescents failing abacavir (ABC), zidovudine (AZT), or TDF containing regimens. METHODS: Drug resistance mutations were analyzed in a retrospective dataset of individuals <19 years of age, failing ABC (n = 293) AZT (n = 288) or TDF (n = 69) based treatment. Pol sequences were submitted to Stanford HIVdb v8.9. Genotypic susceptibility scores were calculated for various DTG-containing regimens. RESULTS: Genotypes were assessed for 650 individuals with a median age of 14 years (IQR 10-17 years). More individuals failed a protease inhibitor (PI)-based (78.3%) than a non-nucleoside reverse transcriptase inhibitors (NNRTI)-based (21.7%) regimen. Most individuals in the AZT group (n = 288; 94.4%) failed a PI-based regimen, compared with 71.0% and 64.2% in the TDF (n = 69) and ABC group (n = 293). Genotypic sensitivity scores <2 to TLD were observed in 8.5% and 9.4% of ABC- and AZT-exposed individuals, compared with 23.2% in the TDF group. The M184V mutation was most often detected in the ABC group (70.6%) versus 60.0% and 52.4% in TDF and AZT groups. The presence of K65R was rare (n = 13, 2.0%) and reduced TLD susceptibility was commonly caused by accumulation of nucleoside reverse transcriptase inhibitor (NRTI) mutations. CONCLUSIONS: Cross-resistance to TDF was limited, further reducing concerns about use of transition to TLD in children and adolescents. The NADIA trial has subsequently shown that patients failing a TDF/3TC/EFV regimen can safely be transitioned to a TLD regimen but we do not have data for patients failing an ABC/3TC/NNRTI or PI regimens. Frequent virological monitoring is recommended after switch to DTG, especially in children continuing ABC in the backbone. Clinical studies correlating predicted resistance with clinical outcomes, especially in settings without access to genotyping, are required.
Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Child , HIV Infections/drug therapy , Heterocyclic Compounds, 3-Ring , Humans , Lamivudine/therapeutic use , Oxazines , Piperazines , Protease Inhibitors/therapeutic use , Pyridones , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Tenofovir/therapeutic use , Zidovudine/therapeutic useABSTRACT
OBJECTIVE: To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. DESIGN: We included data on children initiating ART between 2004 and 2016 at less than 16âyears old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180âdays. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180âdays of ART start were excluded. METHODS: The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. RESULTS: Among 53â674 children included, 23â437 (44%) had a care interruption, of which 10â629 (20%) had a first care interruption within 6 months on ART and 12â808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). CONCLUSION: The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.
Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Africa, Southern , Anti-HIV Agents/therapeutic use , Child , Databases, Factual , HIV Infections/drug therapy , Humans , Proportional Hazards ModelsABSTRACT
BACKGROUND: Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described. METHODS: Sixty-three neonates diagnosed with HIV-1 <48 hours after birth in Johannesburg, South Africa, were started on ART as soon as possible. Fifty-nine (94%) infants received nevirapine prophylaxis from birth until ART start. Viably preserved peripheral blood mononuclear cells (PBMCs) collected at regular intervals to 48 weeks, and from mothers at enrollment, were tested using integrase-targeted, semi-nested, real-time quantitative hydrolysis probe (TaqMan) PCR assays to quantify total HIV-1 subtype C viral DNA (vDNA). Predictors were investigated using generalized estimating equation regression. RESULTS: Thirty-one (49.2%) infants initiated ART <48 hours, 24 (38.1%) <14 days, and 8 (12.7%) >14 days of birth. Three-quarters were infected despite maternal antenatal ART (however, only 9.5% of women had undetectable viral load closest to delivery) and 86% were breastfed. Higher infant CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART were associated with lower vDNA in the first 48 weeks after ART start. No antenatal maternal ART and breastfeeding were also associated with lower vDNA. Older age at ART initiation had a discernible negative impact when initiated >14 days. CONCLUSIONS: Among very early treated infants, higher CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART, infection occurring in the absence of maternal antenatal ART, and breastfeeding were associated with lower levels of HIV-1 DNA in the first 48 weeks of treatment. Clinical Trials Registration. clinicaltrials.gov (NCT02431975).
Subject(s)
Anti-HIV Agents , HIV Infections , HIV-1 , Anti-HIV Agents/therapeutic use , DNA, Viral , Female , HIV Infections/prevention & control , HIV-1/genetics , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Leukocytes, Mononuclear , Pregnancy , South Africa/epidemiology , Viral LoadABSTRACT
OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.
Subject(s)
Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count/methods , Adolescent , Adult , Africa, Southern , Female , HIV Infections/diagnosis , HIV Infections/drug therapy , Health Policy , Humans , Male , Regression Analysis , Viral Load , Young AdultABSTRACT
BACKGROUND: Tenofovir disoproxil fumarate (TDF) is included in first-line antiretroviral treatment (ART) for adolescents living with HIV (ALWH). Associated toxicities remain a concern. OBJECTIVE: We evaluated bone and renal safety outcomes in virologically suppressed South African ALWH after switching to TDF. METHOD: We recruited virally suppressed (< 100 copies/mL) adolescents, aged 15-20 years, who switched from an abacavir (ABC)-based to a TDF-based efavirenz regimen. Bone mass and renal function were assessed at Week 0 and at Week 24 after the switch to TDF using dual-energy X-ray absorptiometry (DXA) and serum renal markers. A change in the lumbar spine (LS) and the whole-body less head (WBLH) bone mineral density (BMD) Z-scores and the estimated glomerular filtration rate (eGFR) between the two measures were compared (paired t-tests) and stratified by sex. RESULTS: Fifty participants (48% male), with a median duration of prior ART of 11.4 years, were enrolled. Among 47 participants with 24-week DXA results, 15 (32%) had either no change or a decreased LS-BMD after the switch, with a mean change of -1.6%. Overall, more female participants experienced this outcome: 58% versus 4%, P < 0.0001. The mean change (standard deviation) in the LS-Z-score was -0.03 (0.25) and in the WBLH-Z-score was 0.02 (0.24). A decrease in the eGFR from 132.2 to 120.4 was observed (P = 0.0003); however, the levels remained clinically acceptable. CONCLUSION: South African ALWH switching from abacavir to TDF-based ART experienced statistically significant decreases in eGFR but not in LS and WBLH BMD. Female ALWH were more likely to experience a decrease in LS-BMD and may require closer monitoring.
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The increased coverage of antiretroviral therapy has resulted in a decrease in the positive predictive value (PPV) and diagnostic sensitivity of early infant diagnosis assays. To evaluate the diagnostic performance of the Aptima HIV-1 Quant DX assay (Aptima) in detecting HIV infection at birth. The study was a cross-sectional laboratory based evaluation using whole blood DBS specimens. Samples were collected from HIV-exposed neonates at birth at two paediatric facilities in Gauteng between 1st March 2018 - 31st January 2020. Performance of the Aptima compared to the Cobas® AmpliPrep/Cobas® TaqMan HIV-1 Qualitative Test v2.0 was calculated using a two-by-two table and reported as proportions with 95% confidence intervals. A total of 363 infants met the inclusion criteria of which 4 (1.1%) had an Aptima result discordant with CAP/CTM HIV status: two (50%) negative and two (50%) positive. The Aptima assay had a sensitivity of 93.75% (95% CI: 79.19%-99.23%), specificity of 99.4% (95% CI: 97.83%-99.93%), PPV of 93.75% (95% CI: 78.98%-98.36%), negative predictive value of 99.4% (95% CI: 97.73%-99.84%), and overall accuracy of 98.9% (95% CI: 97.2%-99.7%). The Aptima yielded an error code on 37 (10.19%) results, of which 35 (94.59%) were resolved on repeat testing. Of the 32 HIV-detected specimens, 20 had a plasma VL result available (18 on Abbott and 2 on Cobas). The absolute median difference was 0.66 log10 (IQR: 0.36-1.71). The Aptima demonstrated good EID performance and can be considered as a qualitative EID assay.
Subject(s)
HIV Infections/diagnosis , HIV-1/genetics , Molecular Diagnostic Techniques/standards , Neonatal Screening/methods , Reagent Kits, Diagnostic/standards , Viral Load/standards , Cross-Sectional Studies , HIV Infections/blood , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Molecular Diagnostic Techniques/methods , RNA, Viral/blood , Sensitivity and Specificity , South Africa , Viral Load/methodsABSTRACT
BACKGROUND: The proportion of children living with HIV and receiving antiretroviral therapy (ART) in sub-Saharan Africa has increased greatly since 2006, yet the changes in their demographic characteristics and treatment outcomes have not been well described. We examine the trends in characteristics and outcomes of children living with HIV who were younger than 5 years at ART initiation, and compare outcomes over time and across country income groups. METHODS: We conducted a retrospective cohort analysis of data from children living with HIV who were younger than 5 years at ART initiation from 45 paediatric sites in 16 low-income, lower-middle-income, and upper-middle-income countries in sub-Saharan Africa (Benin, Burundi, Côte d'Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe). Outcomes were trends in patient characteristics at ART initiation (age, weight, height, and CD4%), and comparisons of mortality and loss to follow-up during ART over time and in various economic settings. We identified risk factors for mortality using Cox proportional hazards models. Each participating region had relevant institutional ethics review board approvals to contribute data to the analysis. FINDINGS: We included 32 221 children living with HIV and initiating ART younger than 5 years between Jan 1, 2006, and Dec 31, 2017. Median age at ART initiation was 20·4 months (IQR 9·4-36·0) in 2006-10, 19·2 months (8·3-33·6) in 2011-13, and 19·2 months (8·8-33·7) in 2014-17. Median age at ART initiation was 13·2 months (IQR 4·7-26·8) in upper-middle-income countries, 22·6 months (13·2-37·5) in lower-middle-income countries and 24·2 months (13·5-39·1) in low-income countries. The proportion of children initiating ART younger than 3 months increased from 770 (5·1%) of 14 943 children in 2006-10 to 728 (10·0%) of 7290 children in 2014-17. The proportion of children initiating ART with severe immunosuppression decreased from 5469 (74·7%) of 7314 children for whom CD4% data were available in 2006-10 to 2353 (55·2%) of 4269 children in 2014-17. Mortality at 24 months on ART decreased from 970 (6·5%) of 14 943 children in 2006-10 to 214 (2·9%) of 7290 children in 2014-17. Loss to follow-up was 20·5% (95% CI 20·1-21·0) overall, and was similar across time periods. In multivariable analysis, lower mortality was observed for more recent ART initiation cohorts (adjusted hazard ratio 0·70, 95% CI 0·63-0·79 for 2011-13; 0·53, 0·45-0·72 for 2014-17 vs 2006-10) and for those residing in an upper-middle-income country (0·42, 0·35-0·49 vs low-income countries). INTERPRETATION: Mortality declined significantly after universal ART recommendations for children younger than 2 years in 2010 and children younger than 5 years in 2013. However, substantial variations persisted across country income groups, and one in five children continue to be lost to follow-up. Targeted interventions are required to improve outcomes of children living with HIV, especially in the poorest countries. FUNDING: National Institute of Allergy and Infectious Disease.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Africa, Northern/epidemiology , Child , Child, Preschool , HIV Infections/economics , HIV Infections/epidemiology , HIV Infections/mortality , Humans , Income , Infant , Male , Poverty , Proportional Hazards Models , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION: Providing easily accessible, quick and accurate human immunodeficiency virus (HIV) testing services (HTS) is central to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets. Rapid diagnostic tests (RDTs) for HIV are affordable and technically easy to perform. Two positive RDTs from different manufacturers are required to make a diagnosis of HIV in South Africa. Difficulty arises when there are discordant results from the two kits. In this case report, we will discuss four instances of false-positive RDTs. PATIENT PRESENTATION: Case 1 is a 10-year-old female, referred for initiation of antiretroviral treatment (ART). She was diagnosed using two of the same brand RDT at her local clinic. Case 2 is a 21-year-old female who presented to obstetric admissions in labour. Case 3 is a 39-year-old female who was screened for HIV during a routine antenatal appointment. Case 4 is a 22-year-old female who was admitted 21 days postpartum with puerperal sepsis. All four cases had discordant RDTs when screened for HIV at our facility. MANAGEMENT AND OUTCOME: The results of all the investigations conducted on all four patients confirmed HIV negative status. The reference laboratory verified the results and reran the RDTs, which remained discordant. This confirmed a false-positive result in all four cases with the screening RDT. CONCLUSION: With high numbers tested and a low yield of new cases, each individual case of discordancy may cause unnecessary distress, confusion and treatment, particularly in high-risk scenarios like pregnancy. Trends of false-positive and discordant RDT results should be monitored and inform HTS guidelines.
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Mode of HIV acquisition for adolescents with HIV is often not recorded within routine healthcare databases. Hence, age at enrollment in HIV care is often used as a proxy for perinatal versus nonperinatal infection. Using routine cohort data from adolescents presenting for HIV care 10-14 years of age, we developed logistic regression models to predict likely mode of infection.
Subject(s)
Disease Transmission, Infectious/classification , HIV Infections/epidemiology , HIV Infections/etiology , HIV Infections/transmission , Adolescent , Age Factors , Area Under Curve , Child , Female , Humans , Infectious Disease Transmission, Vertical , Male , Predictive Value of Tests , ROC Curve , Routinely Collected Health DataABSTRACT
BACKGROUND AND OBJECTIVES: Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with non-perinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence. DESIGN: A retrospective cohort study. METHODS: We included ALPHIV who initiated ART before age 9.5âyears in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004-2016); with viral load (VL) values <400âcopies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs. RESULTS: We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex. CONCLUSIONS: As adolescents age between 10 and 14âyears, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
Subject(s)
Anti-HIV Agents , HIV Infections , Adolescent , Adult , Africa, Southern , Anti-HIV Agents/therapeutic use , Child , Female , HIV Infections/drug therapy , Humans , Male , Retrospective Studies , South Africa/epidemiology , Viral LoadABSTRACT
BACKGROUND: With expansion of antiretroviral therapy (ART) programs, transmission rates are low but new infant infections still occur. We investigated predictors of pre-ART viral load (VL) and CD4+ T-cell counts and percentages in infants diagnosed with HIV at birth in a setting with high coverage of maternal ART and infant prophylaxis. METHODS: As part of an early treatment study, 97 infants with confirmed HIV-infection were identified at a hospital in Johannesburg, South Africa. Infant VL and CD4+ T-cell parameters were measured before ART initiation. Data were collected on maternal characteristics, including VL, CD4+ T-cell counts and ART, and infant characteristics, including sex, birth weight, and mode of delivery. RESULTS: Pre-ART, median infant VL was 28,405 copies/mL [interquartile range (IQR): 2515-218,150], CD4+ T-cell count 1914 cells/mm (IQR: 1474-2639) and percentage 40.8% (IQR: 32.2-51.2). Most (80.4%) infants were born to mothers who received ART during pregnancy and 97.9% of infants received daily nevirapine prophylaxis until ART initiation at median of 2 days of age (IQR: 1-7). Infant pre-ART VL was more likely to be ≥1000 copies/mL when their mothers had VL ≥1000 copies/mL [Odds Ratio (OR): 6.88, 95% confidence interval (CI): 2.32-20.41] and was higher in boys than girls (OR: 3.29, 95% CI: 1.07-9.95). Lower maternal CD4+ T-cell count (<350 cells/mm) was associated with lower infant CD4+ T-cell count (<1500 cells/mm) (OR: 3.59, 95% CI: 1.24-10.43). CONCLUSIONS: Pre-ART VL and CD4+ T-cell parameters of intrauterine-infected infants were associated with VL and CD4+ T-cell counts of their mothers. Maternal ART during pregnancy may begin treatment of intrauterine infection and may mask the severity of disease in infected infants identified in the current era with high-maternal ART coverage.