Can a routine peri-partum HIV counselling and testing service for women improve access to HIV prevention, early testing and treatment of children?

MSc (Med), Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, 2009Context Prevention of mother to child transmission (PMTCT) of HIV relies on identification of HIV-positive pregnant women at the first antenatal visit and at time points thereafter. As not all women who attend antenatal care initially agree to test or maintain an HIV-negative status the lack of re-establishing HIV prevalence at delivery may result in missed prevention opportunities and a false impression of PMTCT coverage. Objectives To assess whether a routine peri-partum HIV counseling and testing service improves access to HIV prevention, testing and care of infants by identifying additional HIV-positive women at the time of delivery. To assess the effect on the PMTCT coverage indicator when HIV prevalence is reestablished in the delivery population. Design and Patients All women 18 years or older with live births in the labour and postnatal wards of the Rahima Moosa Mother and Child Hospital (RMMCH) were interviewed and invited to enrol irrespective of their need to retest/test for HIV or their potential refusal of an HIV test. Rapid HIV antibody tests were offered to women who had no HIV result, reported an HIV-negative result performed more than six weeks prior to delivery or reported an HIV result discrepant with her documented result. vi Test acceptance and HIV prevalence were calculated for the enrolled population. The rate of return and results for early infant diagnosis in HIV-exposed infants and the follow-up of infected infants were documented. HIV polymerase chain reaction (PCR) results for infants not returning to the facility were retrieved from the National Health Laboratory Services database. Results Between 9th April 2008 and the 23rd of September 2008 there were 5169 women with live births. A total of 3684 (71.3%) of the 5169 women delivering were interviewed and 2419 (46.8%) were enrolled. Of the women enrolled, 2140 (88.5%) reported a known HIV status and 490 (22.9%) of these were HIV-positive. After counseling and testing, an additional 101 HIV-positive women were identified increasing the number of HIV-positive women by 20.6%. An additional 177 women were identified as being HIV-negative. The true infant PMTCT coverage increased by 17% as a result of newly identified HIV-positive women. Of 591 HIV-exposed infants identified, 284 (48.0%) underwent PCR testing at RMMCH or surrounding facilities and 16 (5.6%) tested PCR-positive. Of the infants expected to return to RMMCH for PCR testing 155/203 (76.4%) antenataly diagnosed versus 12/83 (14.5%) newly diagnosed women returned with their infants (p<0.001). Ten HIVinfected infants were diagnosed at RMMCH of which nine were in care with six initiated on antiretrovirals

Virologic failure and second-line antiretroviral therapy in children in South Africa--the IeDEA Southern Africa collaboration

Article approval pendingWith expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa

Growth of HIV-exposed uninfected infants in the first 6 months of life in South Africa: The IeDEA-SA collaboration

BACKGROUND: HIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life. METHODS: This is a retrospective cohort based on routine clinical data from two South African PMTCT programmes. Data were collected between 2007 and 2013. Linear regression assessed factors affecting birth weight-for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed effects models. RESULTS: We assessed the growth of 2621 HEU infants (median birth WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers with CD4 <200 cells/μl delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 ≥500 cells/μl. Similarly, mothers who did not receive antiretroviral drugs delivered infants with a lower birth WAZ (adjusted ß -0.39 [95% CI -0.67; -0.11], p = 0.007) compared to mothers who received antenatal antiretrovirals. Infants with a birth weight <2 500g (ß 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight ≥2 500g. Infants with any breastfeeding exposure experienced slower longitudinal growth compared to formula fed infants (adjusted ß -0.012 [95% CI 0.021; -0.003], p = 0.011). CONCLUSION: Less severe maternal disease and the use of antiretrovirals positively impacts birth weight in this cohort of South African HEU infants. Formula feeding was common with breastfed infants experiencing marginally slower longitudinal growth

Monitoring the South African National Antiretroviral Treatment Programme, 2003-2007: the IeDEA Southern Africa collaboration.

OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting

Abacavir safety and effectiveness in young infants with HIV in South African observational cohorts.

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

Recommendations for the management of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme

Indeterminate HIV PCR results represent missed diagnostic opportunities within South Africa’s early infant diagnosis programme. These results not only delay diagnosis and appropriate management but are also a source of confusion and apprehension amongst clinicians and caregivers. We describe the extent of indeterminate HIV PCR results within South Africa’s early infant diagnosis programme and provide recommendations for the management of these cases, both in terms of laboratory practice and the clinical care of the infants.They also thank the United Nations Children’s Emergency Fund (UNICEF) for partial funding of this work. A.H.M. acknowledges the Discovery Foundation for financial support.http://www.sajhivmed.org.zaam2016Medical Virolog

Lamivudine Monotherapy as a holding regimen for HIV-positive children

Background In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes. Methods We describe the characteristics of children (age 90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART. Findings We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3–14.6), duration on cART was 3.6 years (IQR 2.0–5.9) and median CD4 count was 605.5 cells/μL (IQR 427–901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7–55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3–73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART. Interpretation Most patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available

Field Performance and Diagnostic Accuracy of a Low-Cost Instrument-Free Point-of-Care CD4 Test (Visitect CD4) Performed by Different Health Worker Cadres among Pregnant Women

Measuring CD4 counts remains an important component of HIV care. The Visitect CD4 is the first instrument-free low-cost point-of-care CD4 test with results interpreted visually after 40 min, providing a result of 350 CD4 cells/mm3. The field performance and diagnostic accuracy of the test was assessed among HIVinfected pregnant women in South Africa. A nurse performed testing at the point-ofcare using both venous and finger-prick blood, and a counselor and laboratory staff tested venous blood in the clinic laboratory (four Visitect CD4 tests/participant). Performance was compared to the mean CD4 count from duplicate flow cytometry tests on venous blood (FACSCalibur Trucount). In 2017, 156 patients were enrolled, providing a total of 624 Visitect CD4 tests (468 venous and 156 finger-prick samples). Of 624 tests, 28 (4.5%) were inconclusive. Generalized linear mixed modeling showed better performance of the test on venous blood (sensitivity 81.7%; 95% confidence interval [CI] 72.3 to 91.1]; specificity 82.6%, 95% CI 77.1 to 88.1) than on finger-prick specimens (sensitivity 60.7%; 95% CI 45.0 to 76.3; specificity 89.5%, 95% CI 83.2 to 95.8; P 0.001). No difference in performance was detected by cadre of health worker (P 0.113) or between point-of-care versus laboratory-based testing (P 0.108). Adequate performance of Visitect CD4 with different operators and at the point of care, with no need of electricity or instrument, shows the potential utility of this device, especially for facilitating decentralization of CD4 testing services in rural areas

Virologic response to efavirenz-based first-line antiretroviral therapy in children with previous exposure to antiretrovirals to prevent mother-to-child transmission

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6–18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11)

Early mortality and loss to follow-up in HIV-infected children starting antiretroviral therapy in Southern Africa.

BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level