Southern African HIV Clinicians Society Guideline for the clinical management of syphilis.

Syphilis, 'the great imitator', caused by Treponema pallidum infection, remains a complex and multifaceted disease with a rich history of clinical diversity. This guideline aims to be a comprehensive guide for healthcare workers in Southern Africa, offering practical insights into the epidemiology, pathogenesis, clinical manifestations, diagnostic testing, therapeutic principles, and public health responses to syphilis. Although the syphilis burden has declined over the years, recent data indicate a troubling resurgence, particularly among pregnant women and neonates. This guideline highlights the diagnostic challenges posed by syphilis, stemming from the absence of a single high-sensitivity and -specificity test. While treatment with penicillin remains the cornerstone of treatment, alternative regimens may be used for specific scenarios. We highlight the importance of thorough patient follow-up and management of sex partners to ensure optimal care of syphilis cases. In the context of public health, we emphasise the need for concerted efforts to combat the increasing burden of syphilis, especially within high-risk populations, including people living with HIV.

Optimised paediatric antiretroviral treatment to achieve the 95-95-95 goals.

While the progress towards reaching the UNAIDS 95-95-95 targets in South African adults seems promising, the progress in the paediatric population is lagging far behind; only 79% percent of children living with HIV know their status. Of these, only 47% are on treatment, and a mere 34% of those are virally suppressed. Thus, virological suppression has been attained in only 13% of children living with HIV in South Africa. Multiple factors contribute to the high treatment failure rate, one of them being a lack of paediatric-friendly antiretroviral treatment (ART) formulations. For example, the Lopinavir/ritonavir syrup, which is the current mainstay of ART for young children, has an extremely unpleasant taste, contributing to the poor tolerability and lack of adherence by children using the formulation. Furthermore, the lack of appropriate formulations limits the optimisation of regimens, especially for young children and those who cannot swallow tablets. Switching from syrups to dispersible tablets will improve ease of administration and adherence and result in cost-saving. Despite the approval of simplified paediatric-friendly formulations internationally, including other sub-Saharan African countries, unnecessary delays are experienced in South Africa. Clinician groups and community organisations must speak up and demand that approvals be expedited to ensure the delivery of life-changing and life-saving formulations to our patients as a matter of urgency.

Bone outcomes in virally suppressed youth with HIV switching to tenofovir disoproxil fumarate.

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.

False-positive rapid diagnostic tests in paediatric and obstetric patients in South Africa.

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.

Mental health, substance use and viral suppression in adolescents receiving ART at a paediatric HIV clinic in South Africa.

INTRODUCTION: Mental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders. METHODS: Adolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre-screening questions followed by full screening (conditional on positive pre-screening) for depression (Patient Health Questionnaire-9 [PHQ-9]), suicide (Adolescent Innovations Project [AIP]-handbook), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), post-traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC-PTSD-5]) and substance use (CAGE Adapted to Include Drugs [CAGE-AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening. RESULTS: Out of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre-screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ-9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD-7 ≥10), 38 (3.2%) for PTSD (PC-PTSD-5 ≥3), 18 (1.7%) for substance use (CAGE-AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load. CONCLUSIONS: ALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care.

12-month outcomes of HIV-infected infants identified at birth at one maternity site in Johannesburg, South Africa: an observational cohort study.

BACKGROUND: Initiation of antiretroviral therapy (ART) following diagnosis of HIV infection at birth is an emerging area of paediatric HIV care. We present outcomes of HIV-infected infants identified at birth at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. METHODS: From September, 2013 (era 1), only high-risk HIV-exposed infants were offered diagnostic HIV PCR tests at birth. From June, 2014 (era 2), all HIV-exposed infants were offered laboratory-based diagnostic PCR tests. From October, 2014 (era 3), point of care (POC) diagnostic PCR tests were also done if staff availability allowed. We describe time to ART initiation, mortality, retention in care, and viral suppression among the HIV-infected infants identified across these eras. FINDINGS: We tested 5449 HIV-exposed infants who were born between Sept 1, 2013, and June 30, 2016. 88 neonates with confirmed HIV infection were identified and included in the study, of which 86 (98%) started ART. Median age at ART initiation decreased from 9 days (IQR 6-25) in eras 1 and 2 to 2 days (1-8) in era 3. In era 3, more neonates who were co-tested with POC testing started ART within 48 h of birth (29 [83%] of 35; median 1 day [IQR 1-2]) than infants who were not co-tested (one [4%] of 29; median 6 days [5-10]). The probability of mortality by 12 months across the eras was 14% (95% CI 8-24) and did not differ by era. Of the 72 infants who survived and initiated ART at the site, 56 (78%) were retained at 12 months. Of the 56 infants retained in care, 40 (71%) had a viral load less than 400 copies per mL at 12 months, with no differences between eras (p=0·23). INTERPRETATION: HIV-infected infants can be identified at birth and ART can be initiated within hours to days. Although most infants in our cohort started ART, mortality remained unacceptably high with suboptimal retention and viral suppression. Reducing mortality and improving retention and viral suppression remain urgent priorities. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institute of Allergy and Infectious Disease, National Institutes of Health, USAID/PEPfAR, and the South African National HIV Programme.

Guideline on the management of occupational and non-occupational exposure to the human immunodeficiency virus and recommendations for post-exposure prophylaxis: 2015 Update.

This guideline is an update of the post-exposure prophylaxis (PEP) guideline published by the Southern African HIV Clinicians Society in 2008. It updates the recommendations on the use of antiretroviral medications to prevent individuals who have been exposed to a potential HIV source, via either occupational or non-occupational exposure, from becoming infected with HIV. No distinction is made between occupational or non-occupational exposure, and the guideline promotes the provision of PEP with three antiretroviral drugs if the exposure confers a significant transmission risk. The present guideline aligns with the principles of the World Health Organization PEP guidelines (2014), promoting simplification and adherence support to individuals receiving PEP.

Guideline on the Management of Occupational and Non-Occupational Exposure to the Human Immunodeficiency Virus and Recommendations for Post-Exposure Prophylaxis: 2015 Update

This guideline is an update of the post-exposure prophylaxis (PEP) guideline published by the Southern African HIV Clinicians Society in 2008. It updates the recommendations on the use of antiretroviral medications to prevent individuals who have been exposed to a potential HIV source; via either occupational or non-occupational exposure; from becoming infected with HIV. No distinction is made between occupational or non-occupational exposure; and the guideline promotes the provision of PEP with three antiretroviral drugs if the exposure confers a significant transmission risk. The present guideline aligns with the principles of the World Health Organization PEP guidelines (2014); promoting simplification and adherence support to individuals receiving PEP

Poor early virologic performance and durability of abacavir-based first-line regimens for HIV-infected children.

BACKGROUND: Concerns about stavudine (d4T) toxicity have led to increased use of abacavir (ABC) in first-line pediatric antiretroviral treatment (ART) regimens. Field experience with ABC in ART-naïve children is limited. METHODS: Deidentified demographic, clinical and laboratory data on HIV-infected children initiating ART between 2004 and 2011 in a large pediatric HIV treatment program in Johannesburg, South Africa, were used to compare viral suppression at 6 and 12 months by initial treatment regimen, time to suppression (<400 copies/mL) and rebound (>1000 copies/mL after initial suppression). Adjusted logistic regression was used to investigate confounders and calendar effects. RESULTS: Two thousand thirty-six children initiated either d4T/3TC- or ABC/3TC-based first-line regimens in combination with either boosted lopinavir (LPV/r) or efavirenz (EFV). 1634 received d4T regimens (LPV/r n = 672; EFV n = 962) and 402 ABC regimens (LPV/r n = 192; EFV n = 210). At 6 and 12 months on ART, viral suppression rate was poorer in ABC versus d4T groups within both the LPV/r and EFV groups (P < 0.0001 for all points). In ABC groups, time to suppression was significantly slower (log-rank P < 0.0001 and P = 0.0092 for LPV/r- and EFV-based, respectively) and time to rebound after suppression significantly faster (log-rank P = 0.014 and P = 0.0001 for LPV/r- and EFV-based, respectively). Logistic regression confirmed the worse outcomes in the ABC groups even after adjustment for confounders. CONCLUSION: Data from this urban pediatric ART service program show significantly poorer virological performance of ABC compared with d4T-based regimens, a signal that urgently warrants further investigation.

Radiology services for children in HIV- and TB-endemic regions: scope for greater collaboration between radiologists and clinicians caring for children.

There is limited literature documenting the interaction between radiologists and clinicians caring for children, especially in regions where HIV and tuberculosis (TB) are endemic. The dual burden of these diseases in resource-limited settings creates unique challenges for radiographic interpretation and utilization. This review aims to heighten awareness of issues confronting radiologists and clinicians caring for children and to encourage greater collaboration between these two disciplines in HIV- and TB-endemic regions. The Child-Friendly Healthcare Initiative is discussed, emphasizing opportunities to promote child friendliness in radiology services.