Record linkage without patient identifiers: proof of concept using data from South Africa's national HIV program.

Background: Linkage between health databases typically requires identifiers such as patient names and personal identification numbers. We developed and validated a record linkage strategy to combine administrative health databases without the use of patient identifiers, with application to South Africa's public sector HIV treatment program. Methods: We linked CD4 counts and HIV viral loads from South Africa's HIV clinical monitoring database (TIER.Net) and the National Health Laboratory Service (NHLS) for patients receiving care between 2015-2019 in Ekurhuleni District (Gauteng Province). We used a combination of variables related to lab results contained in both databases (result value; specimen collection date; facility of collection; patient year and month of birth; and sex). Exact matching linked on exact linking variable values while caliper matching applied exact matching with linkage on approximate test dates (± 5 days). We then developed a sequential linkage approach utilising specimen barcode matching, then exact matching, and lastly caliper matching. Performance measures were sensitivity and positive predictive value (PPV); share of patients linked across databases; and percent increase in data points for each linkage approach. Results: We attempted to link 2,017,290 lab results from TIER.Net (representing 523,558 unique patients) and 2,414,059 lab results from the NHLS database. Linkage performance was evaluated using specimen barcodes (available for a minority of records in TIER.net) as a "gold standard". Exact matching achieved a sensitivity of 69.0% and PPV of 95.1%. Caliper-matching achieved a sensitivity of 75.7% and PPV of 94.5%. In sequential linkage, we matched 41.9% of TIER.Net labs by specimen barcodes, 51.3% by exact matching, and 6.8% by caliper matching, for a total of 71.9% of labs matched, with PPV=96.8% and Sensitivity = 85.9%. The sequential approach linked 86.0% of TIER.Net patients with at least one lab result to the NHLS database (N=1,450,087). Linkage to the NHLS Cohort increased the number of laboratory results associated with TIER.Net patients by 62.6%. Conclusions: Linkage of TIER.Net and NHLS without patient identifiers attained high accuracy and yield without compromising patient privacy. The integrated cohort provides a more complete view of patients' lab history and could yield more accurate estimates of HIV program indicators.

Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa.

Background: The integrase strand transfer inhibitor (INSTI) dolutegravir is recommended in World Health Organization guidelines, but is associated with weight gain. We evaluated weight change in patients switching from efavirenz to dolutegravir in first-line antiretroviral therapy (ART) in Johannesburg, South Africa. Methods: We conducted a prospective cohort study of adults (≥16 years) of black African ancestry with HIV who initiated ART between January 2010-December 2020. Patients were propensity score-matched 1:1 (unexposed i.e. remaining on efavirenz: exposed i.e. switched from efavirenz to dolutegravir) on sex, age, months on ART, first ART regimen, haemoglobin, body mass index (BMI), blood pressure, viral load and CD4 count. We used linear regression to assess the effect of switching from efavirenz to dolutegravir on weight change and hypertension 12 months after exposure. Findings: We matched 794 patients switching to dolutegravir to 794 remaining on efavirenz. Exposed patients had a higher mean change in weight (1.78 kg; 95% confidence interval (CI):1.04,2.52 kg) from start of follow-up to 12 months vs. unexposed. We also found a 14.2 percentage point increase (95% CI: 10.6,17.7) in the risk of hypertension in those exposed to dolutegravir vs those that remained on efavirenz. Interpretation: In a real-world population, patients gained more weight and were at higher risk of hypertension after switching from efavirenz to dolutegravir than those remaining on efavirenz. Longer follow-up is needed, however, to determine if INSTI-associated weight gain is associated with changes in non-communicable disease risk over the long-term, or whether weight gain is sustained, as seen in clinical trials. Funding: This study has been made possible by the generous support of the American People and the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID), under the terms of cooperative agreement cooperative Agreement 72067419CA00004. In addition to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 1K01MH105320-01A1.

Cohort profile: the South African National Health Laboratory Service (NHLS) National HIV Cohort.

PURPOSE: South Africa's National Health Laboratory Service (NHLS) National HIV Cohort was established in 2015 to facilitate monitoring, evaluation and research on South Africa's National HIV Treatment Programme. In South Africa, 84.8% of people living with HIV know their HIV status; 70.7% who know their status are on ART; and 87.4% on ART are virologically suppressed. PARTICIPANTS: The NHLS National HIV Cohort includes the laboratory data of nearly all patients receiving HIV care in the public sector since April 2004. Patients are included in the cohort if they have received a CD4 count or HIV RNA viral load (VL) test. Using an anonymised unique patient identifier that we have developed and validated to linked test results, we observe patients prospectively through their laboratory results as they receive HIV care and treatment. Patients in HIV care are seen for laboratory monitoring every 6-12 months. Data collected include age, sex, facility location and test results for CD4 counts, VLs and laboratory tests used to screen for potential treatment complications. FINDINGS TO DATE: From April 2004 to April 2018, 63 million CD4 count and VL tests were conducted at 5483 facilities. 12.6 million unique patients had at least one CD4 count or VL, indicating they had accessed HIV care, and 7.1 million patients had a VL test indicating they had started antiretroviral therapy. The creation of NHLS National HIV Cohort has enabled longitudinal research on all lab-monitored patients in South Africa's national HIV programme, including analyses of (1) patient health at presentation; (2) care outcomes such as 'CD4 recovery', 'retention in care' and 'viral resuppression'; (3) patterns of transfer and re-entry into care; (4) facility-level variation in care outcomes; and (5) impacts of policies and guideline changes. FUTURE PLANS: Continuous updating of the cohort, integration with available clinical data, and expansion to include tuberculosis and other lab-monitored comorbidities.

Motivational interviewing retention counseling and adherence to early infant diagnostic HIV testing schedule in South Africa: The PAEDLINK randomized trial.

INTRODUCTION: We report the PAEDLINK randomized trial results on the effect of motivational interviewing (MI) retention counseling on the adherence of postpartum women to the early infant diagnostic human immunodeficiency virus (HIV) testing schedule. METHODS: HIV positive women and their babies were enrolled 3 to 6 days after delivery at 4 midwife obstetric units in the Gauteng province of South Africa and randomized into (A) MI retention counseling and telephonic tracing, (B) biannual telephonic tracing, and (C) standard care. Mother-baby pairs were followed up for 18 months via medical records. The uptake of child HIV tests and maternal retention in the 0 to 6 and 7 to 18 month periods were modeled using Log-binomial regression. RESULTS: Overall, 501/711 enrolled mother-baby pairs received a second HIV polymerase chain reaction test by 6 months (70.0%, 70.5%, and 70.0% in groups A, B, and C, respectively). A higher proportion of intervention children (60.9%) were tested at 7 to 90 days than group B (48.1%, adjusted risk ratio [aRR] 0.8 for B vs A, 95% confidence interval [CI]: 0.7-0.9) and group C children (52.7%, aRR 0.9 for C vs A, 95% CI: 0.9-1.0). Child testing between 7 and 18-months was also higher in group A than C (10.7% A, vs 5.5% C, RR 2.0, 95% CI: 1.0-3.7). However, maternal retention was similar across groups, with 41.6% and 16.3% retained during the 0 to 6 and the 7 to 18-months periods, respectively. CONCLUSION: MI retention counseling can reduce delays in the early infant diagnosis testing schedule for HIV-exposed infants. However, further support is necessary to maximize later HIV tests and maternal retention.

Assessment of facility-level antiretroviral treatment patient status utilizing a national-level laboratory cohort: Toward an understanding of system-level tracking and clinic switching in South Africa.

Background: Most estimates of HIV retention are derived at the clinic level through antiretroviral (ART) patient management systems, which capture ART clinic visit data, yet these cannot account for silent transfers across HIV treatment sites. Patient laboratory monitoring visits may also be observed in routinely collected laboratory data, which include ART monitoring tests such as CD4 count and HIV viral load, key to our work here. Methods: In this analysis, we utilized the NHLS National HIV Cohort (a system-wide viewpoint) to investigate the accuracy of facility-level estimates of retention in care for adult patients accessing care (defined using clinic visit data on patients under ART recorded in an electronic patient management system) at Themba Lethu Clinic (TLC). Furthermore, we describe patterns of facility switching among all patients and those patients classified as lost to follow-up (LTFU) at the facility level. Results: Of the 43,538 unique patients in the TLC dataset, we included 20,093 of 25,514 possible patient records (78.8%) in our analysis that were linked with the NHLS National Cohort, and we restricted the analytic sample to patients initiating ART between 1 January 2007 and 31 December 2017. Most (60%) patients were female, and the median age (IQR) at ART initiation was 37 (31-45) years. We found the laboratory records augmented retention estimates by a median of 860 additional active records (about 8% of all median active records across all years) from the facility viewpoint; this augmentation was more noticeable from the system-wide viewpoint, which added evidence of activity of about one-third of total active records in 2017. In 2017, we found 7.0% misclassification at the facility-level viewpoint, a gap which is potentially solvable through data integration/triangulation. We observed 1,134/20,093 (5.6%) silent transfers; these were noticeably more female and younger than the entire dataset. We also report the most common locations for clinic switching at a provincial level. Discussion: Integration of multiple data sources has the potential to reduce the misclassification of patients as being lost to care and help understand situations where clinic switching is common. This may help in prioritizing interventions that would assist patients moving between clinics and hopefully contribute to services that normalize formal transfers and fewer silent transfers.

Advancing African Medicines Agency through Global Health Diplomacy for an Equitable Pan-African Universal Health Coverage: A Scoping Review.

The African continent is home to 15% of the world's population and suffers from a disease burden of more than 25% globally. In this COVID-19 era, the high burden and mortality are further worsened due to inequities, inequalities such as inadequate health systems, scarce financial and human resources, as well as unavailability of inexpensive medicines of good quality, safety, and efficacy. The Universal Health Coverage ensures that people have access to high-quality essential health services, secure, reliable, and affordable essential medicines and vaccines, as well as financial security. This paper aimed at addressing the critical need for a continental African Medicines Agency (AMA) in addressing the inequities and the role of global health diplomacy in building consensus to support the ratification of the Treaty of AMA. A literature review was done in Scopus, Web of Science, MEDLINE/PubMed, and Google Scholar search engine to identify the critical literature in the context of study objectives. All the articles published after 2015 till 2021 in the context of AMA were included. African Health Strategy 2016-2030 highlighted the importance of an African regulatory mechanism for medicines and medical products. Through global health diplomacy (GHD), the African Union and its partners can negotiate and cooperate in providing infrastructural, administrative, and regulatory support for establishing the AMA. The paper emphasizes the South-South cooperation and highlights the contributions of India and China in the supply of medicines and vaccines to Africa. A strong AMA created through GHD can be a vital instrument in utilizing Trade-Related Aspects of Intellectual Property Rights (TRIPS) flexibilities extension and an ideal partner for European and other regional regulatory authorities seeking to stem the tide of counterfeit, sub-standard, or fake products.

Perceived barriers to the uptake of health services among first-year university students in Johannesburg, South Africa.

BACKGROUND: Young people face many barriers to accessing appropriate health care services including screening for HIV and tuberculosis (TB). The study aimed to identify perceived barriers to the uptake of health services among young adults entering the tertiary education system in South Africa. METHODS: We conducted a cross-sectional study among first-year students aged 18-25 years, registered at one of three universities in Johannesburg, South Africa, in 2017. Participants completed a self-administered paper-based questionnaire. We describe perceived barriers to accessing health services, stratified by gender and recent engagement in TB or HIV services, together with sources of information about HIV and TB. RESULTS: Seven hundred and ninety-two (792) students were included in the study of which 54.8% were female. Perceived barriers to accessing services included long waiting time (n = 342,43.2%), attitude of health workers (n = 263,33.2%), lack of sufficient information/poor health literacy (n = 148,18.7%), and inability to leave/stay away from studies (n = 137,17.3%). Among participants who tested for HIV in the past 6 months (n = 400, 50.5%), waiting time and attitude of health care workers were perceived as barriers to accessing services. Compared to males, females were more likely to view attitudes of health workers (40.3% vs. 25.0%; p = 0.001) and inability to leave/stay away from studies (20.5% vs.13.4%; p = 0.025) as potential barriers. While just over half of the students (50.5%; 400/792) in this study had accessed health services in the past 6 months, very few (15.0%) opted to use campus health services, and even less (5%) reported receiving information about HIV and TB from the university itself. CONCLUSION: Despite perceived barriers to accessing HIV and TB services off campus, fewer than one in five students starting out at university opted to use campus health services. Campus health services could address many of the barriers unique to university students.

The South African National HIV Pregnancy Cohort: evaluating continuity of care among women living with HIV.

BACKGROUND: South Africa is home to more people living with HIV than any other country, including nearly one in three pregnant women attending antenatal care. Access to antiretroviral therapy (ART) has increased substantially since the start of the national ART program in 2004, with > 95% ART coverage during pregnancy and delivery, and vertical transmission of HIV greatly reduced. However, women who initiate ART during pregnancy are at heightened risk of dropping out of care, particularly after delivery, leading to the potential for viral transmission, morbidity and mortality. It is difficult to evaluate the success of policies of expanded access to ART care, and assess continuity of care, due to the lack of a national longitudinal HIV care database. Also, patient movement between unlinked facilities. For the first time on a national level, we propose to utilize routinely-collected laboratory data to develop and validate a cohort of pregnant women living with HIV in South Africa in a way that is uniquely robust to facility transfer. METHODS: Using laboratory test data matched to facility type, we will identify entry to antenatal care to build the cohort, then describe key treatment milestones, including 1) engagement in antenatal care, 2) initiation of ART, 3) HIV viremia, and 4) continuity of HIV care in the postpartum period. Second, we will measure the effect of system-wide factors impacting continuity of care among pregnant women. We will assess policies of expanded treatment access on continuity of care using regression-discontinuity analyses. We then will assess mobility and its effect on continuity of care during and after pregnancy. Third, we will identify individual-level risk factors for loss from HIV care in order to develop targeted interventions to improve engagement in HIV care. DISCUSSION: This work will create the world's largest national cohort of pregnant women living with HIV. This novel cohort will be a powerful tool available to policymakers, clinicians and researchers for improving our understanding of engagement in care among pregnant women in South Africa and assessing the performance of the South African national ART program in caring for pregnant women living with HIV. TRIAL REGISTRATION: N/A (not a clinical trial).

Delays in repeat HIV viral load testing for those with elevated viral loads: a national perspective from South Africa.

INTRODUCTION: In South Africa, HIV patients with an elevated viral load (VL) should receive repeat VL testing after adherence counselling. We set out to use a national HIV Cohort to describe time to repeat viral load testing across South Africa and identify predictors of time to repeat testing. METHODS: We conducted a cohort study of prospectively collected laboratory data. HIV treatment guidelines have changed over time in South Africa, but call for repeat VL testing within six months if 400 to 1000 copies/mL and two to three months if >1000 copies/mL. We included patients with suppressed viral loads (indicating they are on ART) and a first elevated VL (>400 copies/mL) between April 2004 and December 2014. Follow-up began at first elevated VL and continued until repeat testing, loss to follow-up or December 2016. We calculated adjusted hazard ratios (aHR) using Cox proportional hazard models. RESULTS: Of 371,648 patients with a VL > 400, 83.9% (311,790) had a repeat VL, in a median (IQR) of 7.0 (4.1 to 12.2) months. Of those with a first viral load 400 to 1000 copies/mL, 56.4% had a repeat VL within guideline recommended six months (defined as up to nine months), whereas among those >1000 copies/mL only 47.7% had a repeat viral load within guideline recommended two to three months (defined as up to six months). We found a small increase in repeat testing associated with higher VL value (aHR 1.11; 95% CI: 1.10 to 1.12 comparing >1000 vs 400 to 1000 copies/mL) and very low CD4 counts at first elevated VL (aHR 1.16; 95% CI: 1.13 to 1.19 comparing CD4 < 50 vs <500 cells/mm3 ). We also found strong variation in time to repeat VL testing by province. CONCLUSIONS: Median time to repeat viral load testing for those with an elevated viral load was longer than guidelines recommend. Future work should identify whether delays are due to patient or provider factors.

Time of HIV diagnosis, CD4 count and viral load at antenatal care start and delivery in South Africa.

BACKGROUND: Despite the success of prevention of mother to child transmission (PMTCT) program in South Africa, the 30% HIV prevalence among women of childbearing age requires the PMTCT program to be maximally efficient to sustain gains in the prevention of vertical HIV transmission. We aimed to determine the immunologic and virologic status at entry into antenatal care (ANC) and at childbirth among HIV positive women who conceived under the CD4<500 cells/µl antiretroviral therapy (ART) eligibility threshold and universal test and treat (UTT) policies in the Gauteng province of South Africa. METHOD: We conducted a retrospective cohort study of 692 HIV positive adult (>18 years) postpartum women who gave birth between September 2016 and December 2017. Demographic, viral load (VL) and CD4 data at ANC start (3-9 months before delivery) and delivery (3 months before/after) were obtained from medical records of consenting women. We compared CD4≥500 cell/µl and viral load (VL) suppression (<400 copes/ml) rates at ANC start and delivery among women with a pre-pregnancy ART, women known HIV positive but with in-pregnancy ART and newly diagnosed women with in-pregnancy ART. Predictors of having a high CD4 and suppressed VL were assessed by log-binomial regression. RESULTS: Of the 692 participants, 394 (57.0%) had CD4 data and 326 (47.1%) had VL data. Overall women with a pre-pregnancy ART were more likely to start ANC with CD4 count≥500 cell/µl (46.3% vs 24.8%, adjusted risk ratio (aRR) = 1.9; 95% confidence interval (95% CI): 1.4-2.5), compared to newly diagnosed women. This difference was no longer apparent at the time of delivery (aRR 1.2 95% CI: 0.4-3.7). Similarly, viral suppression at delivery was higher among women with pre-pregnancy ART (87.2% vs 69.3%, aRR 1.3, 95% CI: 1.1-1.6) as compared to the newly diagnosed women. Viral suppression rate among newly diagnosed women increased substantially by the time of delivery from 43.5% to 69.3% (p = 0.001). CONCLUSION: These results show that pre-pregnancy ART improves immunologic and virologic control during pregnancy and call for renewed efforts in HIV testing, linkage to ART and viral monitoring.

Prevalence and predictors of postpartum depression by HIV status and timing of HIV diagnosis in Gauteng, South Africa.

BACKGROUND: Postpartum depression (PPD) is a common mental health condition that can compromise the quality of life and functional capacity of mothers and cause health and developmental problems in children born to affected mothers. OBJECTIVES: We set out to measure the prevalence of PPD comparing postpartum HIV-1 infected women with pre-pregnancy HIV care experience, newly diagnosed (in latest pregnancy) HIV-1 infected women and HIV negative women, and to identify predictors of major PPD among these women in a peri-urban clinic in South Africa. METHODS: We conducted a cross-sectional survey of 1151 adult (≥18 years) postpartum HIV-1 infected (690) and HIV negative (461) women who delivered up to 30 days before study enrolment, interviewed after their first post-natal visit (3-6 days post- delivery) at Midwife Obstetric Units in Gauteng, South Africa. PPD was categorised into no depression (CES-D 10 total score <5), low to medium depression (CES-D 10 total score ≥5 and <10) and major depressive symptoms (CES-D 10 total score≥10). We used ordered logistic regression to identify predictors of postpartum depression and report adjusted odds ratio (aOR) and 95% confidence intervals (CIs). RESULTS: Overall 288 (25.0%) women screened positive for postpartum depression, a total of 168 (14.6%) women had low to medium PPD and 120 (10.4%) had major PPD. A higher proportion of HIV negative women experienced PPD, 129/461 (28.0%) among HIV negative vs. 159/690 (23.0%) among HIV-1 infected. Among HIV positive women, there was no meaningful difference in PPD between newly HIV diagnosed and those diagnosed before the most recent pregnancy (aOR 1.3, 95% confidence interval (CI): 0.9-1.8). Predictors of PPD among HIV positive women were living with friends/in a house-share (aOR 0.5 for house-share vs. own home, 95% CI: 0.3-0.9), and attending antenatal care (ANC) for the most recent pregnancy (aOR 0.2 for ANC attendance vs. no ANC attendance, 95% CI: 0.0-0.5). Living with friends/in a house-share was also a predictor of PPD among HIV negative women (aOR 0.4 for house-share vs. own home, 95% CI: 0.2-0.8). CONCLUSIONS AND RECOMMENDATIONS: Targeted symptom screening based on identified risk factors should be considered for postpartum women to increase PPD case-finding and referral to specialised social support services.

Understanding Predictors of Early Antenatal Care Initiation in Relationship to Timing of HIV Diagnosis in South Africa.

Effective prevention of mother-to-child transmission benefits from early presentation to antenatal care (ANC). It is, however, unclear whether a previous HIV diagnosis results in earlier initiation of ANC. We estimated the probability of early ANC initiation among women with a previous HIV-positive diagnosis compared to those who first tested for HIV during ANC and explored determinants of early ANC among HIV-positive women. We conducted an analysis of a cross-sectional survey among 411 HIV-positive adult (>18 years) women who gave birth at midwife obstetrics units in Gauteng between October 2016 and May 2017. Predictors of early ANC (defined as initiating ANC before or at 14 weeks of gestation) were assessed by multivariate log-binomial regression model. Overall, 51% (210) were diagnosed during pregnancy with 89% (188) initiating antiretroviral therapy on the same day of diagnosis. There was no meaningful difference in the timing of ANC initiation between women with previous HIV diagnosis [adjusted risk ratio (aRR) = 1.2; 95% confidence interval (95% CI): 0.9-1.7] compared with those diagnosed during pregnancy. Early ANC was predicted by planned pregnancy [aRR = 1.3; 95% CI: 1.1-1.7], parity (>2 children) [aRR = 0.6; 95% CI: 0.2-0.9] compared to not having a child, and tuberculosis diagnosis [aRR = 2.9; 95% CI: 1.4-6.1]. Our results suggest the need for a targeted intervention among HIV-positive women by improving the quality, content and outreach of ANC services to enhance early ANC uptake, and minimize mother-to-child transmission risk.

Persistent High Burden of Advanced HIV Disease Among Patients Seeking Care in South Africa's National HIV Program: Data From a Nationwide Laboratory Cohort.

Background: The South African national HIV program has increased antiretroviral therapy (ART) coverage over the last decade, supported by policy changes allowing for earlier ART initiation. However, many patients still enter care with advanced (<200 cells/µL) and very advanced (<100 cells/µL) HIV disease. We assessed disease progression at entry to care using nationwide laboratory data. Methods: We constructed a national HIV cohort using laboratory records containing HIV RNA loads and CD4 counts from 2004 to 2016 to determine entry into care. We estimated numbers and proportions of adults with the first CD4 count <100 cells/ µL or 100-199 cells/µL. We calculated relative risks of presenting with advanced disease associated with male sex. Results: 8.04 million first CD4 results were identified. From 2005 to 2011, the proportion of patients entering into care with CD4 count <200 cells/µL declined from 46.8% to 35.6%. From 2011 onward, the proportion of patients entering ART with advanced HIV disease has remained relatively unchanged. In 2016, we estimated that of 654 868 patients entering care, 32.9% had advanced HIV disease, and 16.8% had very advanced HIV disease. Men were almost twice as likely as women (23.1% vs 12.6% ) to enter care with very advanced HIV disease. Conclusions: The proportion of patients presenting with advanced HIV disease in South Africa remains consistently high despite ART scale-up, representing a large and avoidable burden of morbidity. Early HIV diagnosis, rapid linkage to ART and approaches to attract men into early ART initiation should be prioritized.

Predicting the Need for Third-Line Antiretroviral Therapy by Identifying Patients at High Risk for Failing Second-Line Antiretroviral Therapy in South Africa.

Although third-line antiretroviral therapy (ART) is available in South Africa's public sector, its cost is substantially higher than first and second line. Identifying risk factors for failure on second-line treatment remains crucial to reduce the need for third-line drugs. We conducted a case-control study including 194 adult patients (≥18 years; 70 cases and 124 controls) who initiated second-line ART in Johannesburg, South Africa. Unconditional logistic regression was used to assess predictors of virologic failure (defined as 2 consecutive viral load measures ≥1000 copies/mL, ≥3 months after switching to second line). Variables included a social instability index, ART adherence, self-reported as well as diagnosed adverse drug reactions (ADRs), HIV disclosure, depression, and factors affecting access to HIV clinics. Overall 60.0% of cases and 54.0% of controls were female. Mean ages of cases and controls were 41.8 ± 9.6 and 43.3 ± 8.0, respectively. Virologic failure was predicted by ART adherence <90% [odds ratio (OR) 4.7; 95% confidence interval (95% CI): 2.1-10.5], younger age (<40 years of age; OR 0.6; 95% CI: 0.3-1.1), high social instability (OR 3.8; 95% CI: 1.30-11.5), self-reported ADR (OR 1.9; 95% CI: 1.0-3.5), disclosure to friends/colleagues rather than partner/relatives (OR 3.4; 95% CI: 1.3-9.1), and medium/high depression compared to low/no depression (OR 4.4; 95% CI: 1.5-13.4). Our results suggest complex socioeconomic factors contributing to risk of virologic failure, possibly by impacting ART adherence, among patients on second-line therapy in South Africa. Identifying patients with possible indicators of nonadherence could facilitate targeted interventions to reduce the risk of second-line treatment failure and mitigate the demand for third-line regimens.

Determinants of loss to follow-up in patients on antiretroviral treatment, South Africa, 2004-2012: a cohort study.

BACKGROUND: The number of Human Immunodeficiency Virus (HIV) infected people eligible for initiation on antiretroviral Therapy (ART) is increasing. ART programmatic success requires that patients who are taking ART remain on treatment and are followed up regularly. This study investigated factors associated with being lost to follow-up, in a cohort of patients enrolled in a pharmacovigilance study in South Africa. METHODS: This was a retrospective observational cohort study performed at one of the Medunsa National Pharmacovigilance Centre's (MNPC) ART sentinel surveillance sites. Loss to Follow-up (LTFU) was defined as "a patient who had been followed up at the sentinel site, who had not had contact with the health facility for 180 days or more since their last recorded expected date of return or if there were 180 days or more between the expected date of return and the next clinic visit". RESULTS: Out of 595 patients, 65.5% (n = 390) were female and 23.4% (n = 139) were LTFU. The median time on ART before LTFU was 21.5 months (interquartile range: 12.9 - 34.7 months). The incidence rate of LTFU was 103 per 1000 person-years in the first year on ART and increased to 405 per 1000 person-years in the eighth year of taking ART. Factors associated with becoming LTFU included not having a committed partner (Adjusted Hazard Ratio (aHR): 2.9, 95% Confidence Interval (CI):1.19-6.97, p = 0.019), being self-employed (aHR: 13.9, 95% CI:2.81 - 69.06, p = 0.001), baseline CD4 count > 200 cells/ml (aHR: 3.8, 95% CI: 1.85-7.85, p < 0.001), detectable last known Viral Load (VL) (aHR: 3.6, 95% CI:1.98-6.52, p < 0.001) and a last known World Health Organisation clinical stage three or four (aHR: 2.0, 95% CI:1.22-3.27, p = 0.006). Patients that previously had an ART adverse event had a lower risk (aHR: 0.6, 95% CI: 0.38 - 0.99, p = 0.044) of becoming LTFU than those that had not. CONCLUSION: The incidence rate of LTFU increases with additional years on ART. Intensified measures to improve patient retention on ART must be prioritised with increasing patient time on ART and in patients that are at increased risk of becoming lost to follow-up.

Relationship between household socio-economic status and under-five mortality in Rufiji DSS, Tanzania.

BACKGROUND: Disparities in health outcomes between the poor and the better off are increasingly attracting attention from researchers and policy makers. However, policies aimed at reducing inequity need to be based on evidence of their nature, magnitude, and determinants. OBJECTIVES: The study aims to investigate the relationship between household socio-economic status (SES) and under-five mortality, and to measure health inequality by comparing poorest/least poor quintile mortality rate ratio and the use of a mortality concentration index. It also aims to describe the risk factors associated with under-five mortality at Rufiji Demographic Surveillance Site (RDSS), Tanzania. METHODS: This analytical cross sectional study included 11,189 children under-five residing in 7,298 households in RDSS in 2005. Principal component analysis was used to construct household SES. Kaplan-Meier survival incidence estimates were used for mortality rates. Health inequality was measured by calculating and comparing mortality rates between the poorest and least poor wealth quintile. We also computed a mortality concentration index. Risk factors of child mortality were assessed using Poisson regression taking into account potential confounders. RESULTS: Under-five mortality was 26.9 per 1,000 person-years [95% confidence interval (CI) (23.7-30.4)]. The poorest were 2.4 times more likely to die compared to the least poor. Our mortality concentration index [-0.16; 95% CI (-0.24, -0.08)] indicated considerable health inequality. Least poor households had a 52% reduced mortality risk [incidence rate ratio (IRR) = 0.48; 95% CI 0.30-0.80]. Furthermore, children with mothers who had attained secondary education had a 70% reduced risk of dying compared to mothers with no education [IRR = 0.30; 95% CI (0.22-0.88)]. CONCLUSION: Household socio-economic inequality and maternal education were associated with under-five mortality in the RDSS. Targeted interventions to address these factors may contribute towards accelerating the reduction of child mortality in rural Tanzania.