• Lamivudine monotherapy as a holding regimen for HIV-positive children.

      Patten, G; Bernheimer, J; Fairlie, L; Rabie, H; Sawry, S; Technau, K; Eley, B; Davies, MA (Public Library of Science, 2018-10-11)
      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 <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >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.
    • The Last and First Frontier--Emerging Challenges for HIV Treatment and Prevention in the First week of Life With Emphasis on Premature and Low Birth Weight Infants

      Cotton, MF; Holgate, S; Nelson, A; Rabie, H; Wedderburn, C; Mirochnick, M (International AIDS Society, 2015-12-02)
      There is new emphasis on identifying and treating HIV in the first days of life and also an appreciation that low birth weight (LBW) and preterm delivery (PTD) frequently accompany HIV-related pregnancy. Even in the absence of HIV, PTD and LBW contribute substantially to neonatal and infant mortality. HIV-exposed and -infected infants with these characteristics have received little attention thus far. As HIV programs expand to meet the 90-90-90 target for ending the HIV pandemic, attention should focus on newborn infants, including those delivered preterm or of LBW.
    • The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure.

      Davies, M-A; Boulle, A; Technau, K; Eley, B; Moultrie, H; Rabie, H; Garone, D; Giddy, J; Wood, R; Egger, M; et al. (2012-09-14)
      Objectives  To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure. Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months. Results  Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%. Conclusion  The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
    • Southern African HIV Clinicians Society guideline for the prevention, diagnosis and management of cryptococcal disease among HIV-infected persons: 2019 update

      Govender, NP; Meintjes, G; Mangena, P; Nel, J; Potgieter, S; Reddy, D; Rabie, H; Wilson, D; Black, J; Boulware, D; et al. (Health and Medical Publishing Group, 2019-11-08)
    • Viral Load Versus CD4⁺ Monitoring and 5-Year Outcomes of Antiretroviral Therapy in HIV-Positive Children in Southern Africa: a Cohort-Based Modelling Study

      Salazar-Vizcaya, L; Keiser, O; Karl, T; Davies, MA; Haas, Andreas D; Blaser, N; Cox, V; Eley, B; Rabie, H; Moultrie, H; et al. (Lippincott Williams & Wilkins, 2014-10-23)
      Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4⁺ to monitor ART. We assessed the benefit of replacing CD4⁺ by viral load monitoring.
    • Virologic response of adolescents living with perinatally acquired HIV receiving antiretroviral therapy in the period of early adolescence (10-14 years) in South Africa.

      Nyakato, P; Schomaker, M; Sipambo, N; Technau, KG; Fatti, G; Rabie, H; Tanser, F; Eley, B; Euvrard, J; Wood, R; et al. (Lippincott, Williams & Wilkins, 2021-01-21)
      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 nonperinatally 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 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/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 nonnucleoside 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 14 years, 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.
    • Where do HIV-infected adolescents go after transfer? - Tracking transition/transfer of HIV-infected adolescents using linkage of cohort data to a health information system platform

      Davies, MA; Tsondai, P; Tiffin, N; Eley, B; Rabie, H; Euvrard, J; Orrell, C; Prozesky, H; Wood, R; Cogill, D; et al. (Wiley, 2017-03-16)
      To evaluate long-term outcomes in HIV-infected adolescents, it is important to identify ways of tracking outcomes after transfer to a different health facility. The Department of Health (DoH) in the Western Cape Province (WCP) of South Africa uses a single unique identifier for all patients across the health service platform. We examined adolescent outcomes after transfer by linking data from four International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) cohorts in the WCP with DoH data.