BACKGROUND: Despite South Africa's substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown OBJECTIVES: Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants METHODS: Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression RESULTS: For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIV-VL <12 weeks before delivery accounted for 83% (n=119/143) of study-derived high-risk exposures and 81% (n=60/74) of missed high-risk exposures. Fewer mothers of high-risk infants had >4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks' gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant CONCLUSION: Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infants

BACKGROUND: Rapid switching from second-line to third-line antiretroviral therapy (TLART) is crucial for achieving viral suppression and reducing illness related to ART failure OBJECTIVES: This retrospective cohort study quantified the waiting periods for TLART initiation after virological failure on second-line therapy was detected, assessed factors associated with delays and assessed the outcomes of patients started on TLART METHOD: Data were abstracted from records of individuals eligible for TLART, and the time to TLART initiation was calculated. Reasons for delays were categorised according to patient, clinician and administrative processes RESULTS: Fifty-four patients were eligible for TLART. The median delay from the date of first viral load > 1000 copies/mL on second-line therapy to the start of TLART was 640 days (interquartile range [IQR]: 451-983 days). Of the patients that failed second-line and had an application for TLART, 41 (75.6%) were eventually initiated on TLART, and 11 (20.4%) died while waiting. Delays were primarily due to non-response to the first unsuppressed viral load while on second-line ART: 467 days (IQR: 232-803 days CONCLUSION: This study showed a prolonged waiting period for TLART initiation mainly between detected high viral load to requesting of resistance tests; many factors could have contributed, including clinicians' delayed responses to elevated viral loads. Mortality was high before TLART could be initiated. The process of TLART initiation needs to be made more efficient. Healthcare services should be strengthened to (1) recognise and manage virological failure early and identify those eligible for resistance testing, (2) ensure access to resistance testing and appropriately skilled clinicians, and (3) streamline approvals and delivery of TLART

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic resulted in unique programmatic opportunities to test hypotheses related to the initiation of antiretroviral treatment (ART) and viral load (VL) suppression during a global health crisis, which would not otherwise have been possible. OBJECTIVES: To generate practice-relevant evidence on the impact of initiating ART pre-COVID-19 versus during the COVID-19 pandemic on HIV VL. METHOD: Logistic regression was performed on data covering 6596 persons with HIV whose VL data were available, out of 36 585 persons who were initiated on ART between 01 April 2019 and 30 March 2021. RESULTS: After controlling for covariates such as age, gender, duration on ART, tuberculosis status at the time of the last visit, and rural vs urban status, the odds of having a VL < 1000 copies/mL were significantly higher for clients who started ART during the COVID-19 pandemic than the year before COVID-19 (adjusted odds ratio [AOR]: 2.50; confidence interval [CI]: 1.55-4.01; P < 0.001). Odds of having a VL < 1000 copies/mL were also significantly higher among female participants than male (AOR: 1.23; CI: 1.02-1.48), among patients attending rural clinics compared to those attending urban clinics (AOR: 1.83; CI: 1.47-2.28), and in clients who were 15 years or older at the time of their last visit (AOR: 1.50; CI: 1.07-2.11. CONCLUSION: Viral loads did not deteriorate despite pandemic-induced changes in HIV services such as the expansion of multi-month dispensing (MMD), which may have played a protective role regardless of the general negative impacts of response to the COVID-19 crises on communities and individuals. What this study adds: This research capitalises on the natural experiment of COVID-19-related changes in HIV services and provides new practice-relevant research evidence..

BACKGROUND: An increasing number of girls living with perinatally acquired HIV (PHIV) are reaching adolescence and adulthood and becoming pregnant. Youth living with PHIV (YLPHIV) may have HIV-associated infections/complications, long-term exposure to antiretroviral treatment (ART), drug resistance and increased psychosocial challenges, which may adversely affect pregnancy outcomes. There is a lack of published studies on pregnancy in YLPHIV in sub-Saharan AfricaOBJECTIVES: To describe characteristics of pregnant South African (SA) YLPHIV and their pregnancy outcomesMETHODS: We retrospectively identified pregnancies in YLPHIV, who were diagnosed with HIV when they were <12 years old and before their first pregnancy (as a proxy for perinatal route of infection), from routinely collected data in Western Cape Province, SA (2007 - 2018). We combined these with pregnancies from a Johannesburg cohort of YLPHIVRESULTS: We identified 258 pregnancies among 232 females living with likely PHIV; 38.8% of pregnancies occurred in YLPHIV <16 years old, 39.1% at age 17-19 years and 22.1% at age >20 years. In recent years, a steady increase in the number of pregnancies in YLPHIV was noted; more than two-thirds occurred during 2016 - 2018. ART was commenced prior to pregnancy in 84.9% of YLPHIV, during pregnancy in 6.6% and was not commenced by pregnancy end date in 8.5%. Of the pregnancies in young women with documented outcomes (88.8%; n=229), 80.3% were live births, 14.4% terminations, 3.1% miscarriages and 2.2% stillbirths. Mother-to-child transmission of HIV occurred in 2.2% of infants, 75.3% were uninfected when last tested and 22.6% had unknown HIV status. Among YLPHIV with CD4 counts available within 12 months of pregnancy end date (n=202), 20.3% had a CD4 count <200 cells/μL, 43.1% CD4 count 200 - 499 cells/uL and 36.6% CD4 count >500 cells/uL. Among those with a viral load (VL) available within 12 months of pregnancy end date (n=219), 66.7% had a VL <400 copies/mL, 5.0% VL 400 - 999 copies/mL and 28.3% VL >1 000 copies/mL. Of 186 neonates, 20.4% were preterm deliveries (<37 weeks' gestation). Among neonates with known birthweight (n=176), the mean birthweight was 2 900 g (95% confidence interval (CI) 2 747 - 2 935 g) and 20.5% had a low birthweight (<2 500 g). One congenital malformation (musculoskeletal) and 2 neonatal deaths were recordedCONCLUSIONS: In recent years, the number of pregnancies in YLPHIV has increased. A considerable proportion of pregnancies occurred in YLPHIV <16 years old. A high proportion of pregnancies was electively terminated. The prevalence of elevated VL and poor immunological status among pregnant YLPHIV is concerning

A recuperação imunológica reflete condições de saúde. Nosso objetivo foi estimar o tempo até a recuperação imunológica e fatores associados em pessoas vivendo com HIV (PVHIV) após de iniciar a terapia antirretroviral (TARV). Foi conduzida uma coorte histórica de PVHIV (> 18 anos) no Estado de Minas Gerais, Brasil, usando bancos de serviços públicos de saúde. Foram incluídos pacientes que iniciaram a TARV entre 2009 e 2018, com linfócitos T-CD4+ e carga viral registrados antes e depois do início da TARV. O desfecho foi a recuperação imunológica, definida como a primeira contagem de T-CD4+ > 500 cel/µL após o início da TARV. As variáveis explanatórias foram idade, sexo, local de residência, ano de início de TARV, carga viral basal, T-CD4+ na linha de base e carga viral e adesão à TARV no seguimento. Foi realizada uma análise descritiva com estimativa de incidência acumulada e taxa de incidência (pessoa-ano). O tempo mediano até a recuperação imunológica foi estimado pelo método Kaplan-Meier. Fatores associados à recuperação imune foram avaliados por meio de regressão de Cox. Entre as 26.430 PVHIV, 8.014 (30%) foram elegíveis. A maioria era do sexo masculino (67%), com média de idade = 38,7 anos, residência em regiões fora da região metropolitana, mediana de T-CD4+ baseline = 228 células/µL (< 200 células/µL = 43%) e mediana de carga viral baseline = 4,7 log10 cópias/mL (carga viral detectável = 99%). Tempo de seguimento = 15.872 pessoas-ano. A incidência acumulativa e a taxa de incidência foram foram 58% (IC95%: 57-58) (n = 4.678) e 29,47 casos/100 pessoas-ano, respectivamente. Tempo mediano até recuperação imune = 22,8 meses (IC95%: 21,9-24,0). Os fatores independentemente associados com recuperação imunológica foram sexo feminino, idade < 38 anos, T-CD4+ basal > 200 células/µL, carga viral detectável (linha de base), adesão à TARV e carga viral indetectável (no seguimento). O tempo até a recuperação imunológica ainda é longo e impactado pelo tratamento precoce e da adesão à TARV.

Immune recovery reflects health conditions. Our goal was to estimate the time it takes to achieve immune recovery and its associated factors, in people living with HIV (PLHIV), after antiretroviral therapy (ART) initiation. A historical cohort study was performed among PLHIV (> 18 years-old) in Minas Gerais State, Brazil, using data from healthcare databases. Patients initiating ART between 2009-2018, with T-CD4+ lymphocytes and viral load recorded before and after antiretroviral therapy were included. The outcome is achievement of immune recovery, defined as the first T-CD4+ > 500 cells/µL after ART initiation. Explanatory variables were age, gender, place of residence, year of ART initiation, baseline viral load and T-CD4+, viral load status, and adherence to ART at follow-up. Descriptive analysis, cumulative, and person-time incidences of immune recovery were estimated. Median-time to immune recovery was estimated using Kaplan-Meier method. Factors associated with immune recovery were assessed by Cox regression. Among 26,430 PLHIV, 8,014 (30%) were eligible. Most were male (67%), mean age 38.7 years, resided in non-central region, median-baseline T-CD4+ = 228 cells/µL (< 200 cells/µL = 43%) and viral load median-baseline = 4.7 log10 copies/mL (detectable viral load = 99%). Follow-up time = 15,872 person-years. Cumulative and incidence rate were 58% (95%CI: 57-58) (n = 4,678) and 29.47 cases/100 person-years, respectively. Median-time to immune recovery was of 22.8 months (95%CI: 21.9-24.0). Women living with HIV, younger than 38 years of age, with T-CD4+ baseline > 200 cells/µL, detectable viral load (baseline), antiretroviral therapy-adherence and undetectable viral load (follow-up) were independently associated with immune recovery. Time to immune recovery remains long and depends on early treatment and antiretroviral therapy-adherence.

La recuperación inmunológica refleja condiciones de salud. Nuestra meta fue estimar el tiempo y los factores asociados a la recuperación inmunológica en personas que viven con VIH (PVVIH), tras iniciar una terapia antirretroviral (TAR). Se realizó sobre una cohorte histórica entre PVVIH (> 18 años de edad) en Minas Gerais, Brasil, usando datos de las bases de datos del sistema de salud. Se incluyeron a pacientes que comenzaron una TAR entre 2009-2018, con T-CD4+ linfocitos y carga viral, registrada antes/después de TAR. El resultado fue el logro de recuperación inmunológica, definida como la primera T-CD4+ > 500 células/µL tras la iniciación TAR. Las variables explicatorias fueron: edad, género, lugar de residencia, año de iniciación TAR, base de referencia de carga viral, base de referencia de T-CD4+ y estatus de la carga viral y adherencia al TAR en el seguimiento. Se estimó: análisis descriptivo, acumulativo e incidencias persona-tiempo de recuperación inmunológica. La media de tiempo para la recuperación inmunológica se estimó usando el método Kaplan-Meier. Los factores asociados con la recuperación inmunológica se evaluaron mediante la regresión de Cox. Entre las 26.430 PVVIH, 8.014 (30%) fueron elegibles. La mayoría eran hombres (67%), media de edad = 38,7 años, residentes en una región no central, media de base de referencia T-CD4+ = 228 células/µL (< 200 células/µL = 43%) y carga viral media de base de referencia = 4,7 log10 copias/mL (carga viral detectable = 99%). El tiempo de seguimiento = 15.872 persona-años. La tasa acumulativa y de incidencia fue 58% (95%CI: 57-58) (n = 4.678) y 29,47 casos/100 persona-años, respectivamente. El tiempo de media para la recuperación inmunológica = 22,8 meses (95%CI: 21,9-24,0). Género femenino, PVVIH < 38 años de edad, T-CD4+ base de referencia > 200 células/µL, carga viral detectable (base de referencia), adherencia al TAR e carga viral indetectable (seguimiento) estuvieron independientemente asociadas con la recuperación inmunológica. El tiempo para la recuperación inmunológica sigue siendo largo y depende de un tratamiento temprano y de adherencia a la TAR.

A recuperação imunológica reflete condições de saúde. Nosso objetivo foi estimar o tempo até a recuperação imunológica e fatores associados em pessoas vivendo com HIV (PVHIV) após de iniciar a terapia antirretroviral (TARV). Foi conduzida uma coorte histórica de PVHIV (> 18 anos) no Estado de Minas Gerais, Brasil, usando bancos de serviços públicos de saúde. Foram incluídos pacientes que iniciaram a TARV entre 2009 e 2018, com linfócitos T-CD4+ e carga viral registrados antes e depois do início da TARV. O desfecho foi a recuperação imunológica, definida como a primeira contagem de T-CD4+ > 500 cel/µL após o início da TARV. As variáveis explanatórias foram idade, sexo, local de residência, ano de início de TARV, carga viral basal, T-CD4+ na linha de base e carga viral e adesão à TARV no seguimento. Foi realizada uma análise descritiva com estimativa de incidência acumulada e taxa de incidência (pessoa-ano). O tempo mediano até a recuperação imunológica foi estimado pelo método Kaplan-Meier. Fatores associados à recuperação imune foram avaliados por meio de regressão de Cox. Entre as 26.430 PVHIV, 8.014 (30%) foram elegíveis. A maioria era do sexo masculino (67%), com média de idade = 38,7 anos, residência em regiões fora da região metropolitana, mediana de T-CD4+ baseline = 228 células/µL (< 200 células/µL = 43%) e mediana de carga viral baseline = 4,7 log10 cópias/mL (carga viral detectável = 99%). Tempo de seguimento = 15.872 pessoas-ano. A incidência acumulativa e a taxa de incidência foram foram 58% (IC95%: 57-58) (n = 4.678) e 29,47 casos/100 pessoas-ano, respectivamente. Tempo mediano até recuperação imune = 22,8 meses (IC95%: 21,9-24,0). Os fatores independentemente associados com recuperação imunológica foram sexo feminino, idade < 38 anos, T-CD4+ basal > 200 células/µL, carga viral detectável (linha de base), adesão à TARV e carga viral indetectável (no seguimento). O tempo até a recuperação imunológica ainda é longo e impactado pelo tratamento precoce e da adesão à TARV.

Immune recovery reflects health conditions. Our goal was to estimate the time it takes to achieve immune recovery and its associated factors, in people living with HIV (PLHIV), after antiretroviral therapy (ART) initiation. A historical cohort study was performed among PLHIV (> 18 years-old) in Minas Gerais State, Brazil, using data from healthcare databases. Patients initiating ART between 2009-2018, with T-CD4+ lymphocytes and viral load recorded before and after antiretroviral therapy were included. The outcome is achievement of immune recovery, defined as the first T-CD4+ > 500 cells/µL after ART initiation. Explanatory variables were age, gender, place of residence, year of ART initiation, baseline viral load and T-CD4+, viral load status, and adherence to ART at follow-up. Descriptive analysis, cumulative, and person-time incidences of immune recovery were estimated. Median-time to immune recovery was estimated using Kaplan-Meier method. Factors associated with immune recovery were assessed by Cox regression. Among 26,430 PLHIV, 8,014 (30%) were eligible. Most were male (67%), mean age 38.7 years, resided in non-central region, median-baseline T-CD4+ = 228 cells/µL (< 200 cells/µL = 43%) and viral load median-baseline = 4.7 log10 copies/mL (detectable viral load = 99%). Follow-up time = 15,872 person-years. Cumulative and incidence rate were 58% (95%CI: 57-58) (n = 4,678) and 29.47 cases/100 person-years, respectively. Median-time to immune recovery was of 22.8 months (95%CI: 21.9-24.0). Women living with HIV, younger than 38 years of age, with T-CD4+ baseline > 200 cells/µL, detectable viral load (baseline), antiretroviral therapy-adherence and undetectable viral load (follow-up) were independently associated with immune recovery. Time to immune recovery remains long and depends on early treatment and antiretroviral therapy-adherence.

La recuperación inmunológica refleja condiciones de salud. Nuestra meta fue estimar el tiempo y los factores asociados a la recuperación inmunológica en personas que viven con VIH (PVVIH), tras iniciar una terapia antirretroviral (TAR). Se realizó sobre una cohorte histórica entre PVVIH (> 18 años de edad) en Minas Gerais, Brasil, usando datos de las bases de datos del sistema de salud. Se incluyeron a pacientes que comenzaron una TAR entre 2009-2018, con T-CD4+ linfocitos y carga viral, registrada antes/después de TAR. El resultado fue el logro de recuperación inmunológica, definida como la primera T-CD4+ > 500 células/µL tras la iniciación TAR. Las variables explicatorias fueron: edad, género, lugar de residencia, año de iniciación TAR, base de referencia de carga viral, base de referencia de T-CD4+ y estatus de la carga viral y adherencia al TAR en el seguimiento. Se estimó: análisis descriptivo, acumulativo e incidencias persona-tiempo de recuperación inmunológica. La media de tiempo para la recuperación inmunológica se estimó usando el método Kaplan-Meier. Los factores asociados con la recuperación inmunológica se evaluaron mediante la regresión de Cox. Entre las 26.430 PVVIH, 8.014 (30%) fueron elegibles. La mayoría eran hombres (67%), media de edad = 38,7 años, residentes en una región no central, media de base de referencia T-CD4+ = 228 células/µL (< 200 células/µL = 43%) y carga viral media de base de referencia = 4,7 log10 copias/mL (carga viral detectable = 99%). El tiempo de seguimiento = 15.872 persona-años. La tasa acumulativa y de incidencia fue 58% (95%CI: 57-58) (n = 4.678) y 29,47 casos/100 persona-años, respectivamente. El tiempo de media para la recuperación inmunológica = 22,8 meses (95%CI: 21,9-24,0). Género femenino, PVVIH < 38 años de edad, T-CD4+ base de referencia > 200 células/µL, carga viral detectable (base de referencia), adherencia al TAR e carga viral indetectable (seguimiento) estuvieron independientemente asociadas con la recuperación inmunológica. El tiempo para la recuperación inmunológica sigue siendo largo y depende de un tratamiento temprano y de adherencia a la TAR.

BACKGROUND: During the era of the Millennium Development Goals (MDG), children were shown to have less access to human immunodeficiency virus (HIV) services than their adult counterparts; hence the call to prioritise children in the implementation of the Sustainable Development Goals (SDGs). However, South African (SA) national data in 2019 indicated that almost 3 years into the implementation of the 90-90-90 strategy, only 59% of children living with HIV had been tested for HIV compared to 90% of adults. OBJECTIVES: To evaluate the access of children to HIV services and record the viral load (VL) suppression rates during the implementation of the 90-90-90 strategy in the City of Johannesburg (COJ), South Africa. METHODS: This study applied a quasi-experimental interrupted time-series (ITS) design using the monthly District Health Information System (DHIS) and National Health Laboratory Services (NHLS) databases spanning the period from 2015 to 2020, that is, before and after the implementation and roll-out of the 90-90-90 strategy. Data were extracted from these databases into MS Excel 2010 spreadsheets and analysed with Stata 15 software from Stata Corp using a two-tailed t-test at a 5% level of significance RESULTS: Overall, a significant increase was observed in the number of individuals tested for HIV, n = 757, p = 0.0086, and retained in care n = 2523, p = 0.001 over the whole period of analysis beginning in April 2015. Adult HIV testing, antiretroviral treatment (ART) initiation and retention in care had been decreasing in absolute numbers over a 10-month period before the intervention. An increase in these three data elements was observed following the implementation of the 90-90-90 program. On the other hand, children aged 0-15 years had demonstrated a significant increase in absolute numbers tested for HIV, n = 171, p = 0.001, but an insignificant increase in number of ART initiations, n = 14.33, p = 0.252, before implementation but a decrease after this. The overall VL suppression rates for children were lower than those of adults. CONCLUSION: Although the COJ has recorded progress in adult HIV testing, ART initiation and retention, children living with HIV aged 0-15 years continue to experience less access to HIV services and lower VL suppression than youths and adults of ≥ 15 years. Therefore, to ensure that the 90-90-90 targets are achieved across different age groups, children must be prioritised so that they can equally access these services with adults

BACKGROUND: The UNAIDS 2020 Global strategy to reduce the transmission of HIV includes ensuring HIV viral load (VL) testing coverage of at least 90% on all patients on antiretroviral therapy (ART). Routine VL monitoring has been shown to result in earlier detection of treatment failure, timely regimen switches, promotion of adherence to treatment and improved survival. We wanted to assess the introduction of the wellness anniversary in improving routine viral load monitoring. OBJECTIVES: We retrospectively assessed effects of the wellness anniversary on routine VL coverage, timeliness and suppression rates. METHOD: The month when the patient initiated ART was designated as the wellness anniversary. On the anniversary month a package of care, which included a routine VL, was delivered. We conducted a retrospective chart audit to assess VL coverage and timeliness between two time periods, from January 2016 to December 2016 (pre-implementation) and from January 2017 to December 2017 (post-implementation. RESULTS: Timeliness of VL testing improved from 27.5% in the pre-implementation cohort to 49.7% in the post-implementation cohort. Our study showed high VL testing coverage before the implementation of the wellness anniversary with an average of 98.3% VL. There was a significant correlation between timeliness and VL suppression (VLS) in the post-implementation group. CONCLUSION: Implementation of the wellness anniversary may improve timeliness of routine VL testing in settings with high VL coverage. Studies looking at the effect of timeliness on VLS and clinical outcomes are needed.

INTRODUCTION: There is very limited published experience with intravenous (IV) antituberculosis (anti-TB) and antiretroviral therapy (ART) especially in children. We have described a human immunodeficiency virus (HIV)-infected child with complicated abdominal tuberculosis who was initially treated with IV anti-TB and a partially IV ART regimen before transitioning to oral therapy PATIENT PRESENTATION: A 3-year-old boy presented with hypovolaemic shock with a 3-day history of inability to pass stools, abdominal distension and bile-stained vomiting. Abdominal ultrasound and X-ray showed small-bowel obstruction. Human immunodeficiency virus antibody testing was positive, and Cluster of Differentiation (CD)4+ lymphocyte count was 56 cells/mL (15%). Xpert Mycobacterium tuberculosis (MTB)/Rifampicin (RIF) Ultra and TB culture on induced sputum detected MTB complex sensitive to rifampicin and isoniazid MANAGEMENT AND OUTCOME: Following laparotomy and closure of bowel perforations, the child was commenced on IV rifampicin, moxifloxacin and amikacin. Amikacin was stopped after 3 days because of nephrotoxicity, and meropenem and IV linezolid were added. After 20 days, ART comprising IV zidovudine, oral lamivudine solution, oral lopinavir/ritonavir solution and additional oral ritonavir solution for super boosting was commenced. By day 40, the patient was well established on oral feeds and was switched to standard oral anti-TB medications. Sputum examined 1 month after starting the treatment was found culture-negative for MTB. After 4 months of treatment, the HIV viral load was < 100 copies/mL. He completed a total of 12 months of anti-TB treatment. CONCLUSION: Despite limited experience and few available IV formulations of standard anti-TB and ARV medications, initial IV therapy may be beneficial for patients in whom oral medication is not an option

BACKGROUND: Pooled testing, or pooling, has been used for decades to efficiently diagnose relatively rare conditions, such as infection in blood donors. Programmes for the prevention of mother-to-child transmission of HIV and for antiretroviral therapy (ART) are being rolled out in much of Africa and are largely successful. This increases the need for early infant diagnosis (EID) of HIV using qualitative nucleic acid testing and for virological monitoring of patients on ART using viral load testing. While numbers of patients needing testing are increasing, infant HIV infections and ART failures are becoming rarer, opening an opportunity for pooled testing approaches. AIM: This review highlights the need for universal EID and viral load coverage as well as the challenges faced. We introduce the concept of pooled testing and highlight some important considerations before giving an overview of studies exploring pooled testing for EID and virological monitoring. RESULTS: For ART monitoring, pooling has been shown to be accurate and efficient; for EID it has not been tried although modelling shows it to be promising. The final part attempts to place pooling into the context of current mother-to-child transmission of HIV and ART programmes and their expected trajectories over the next years. CONCLUSION: Several points warrant consideration: pre-selection to exclude samples with an elevated pre-test probability of positivity from pooled testing, the use of dried blood or plasma spots, and choosing a pooling strategy that is both practically feasible and economical. Finally, novel ideas are suggested to make pooling even more attractive.

Rilpivirine, a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), is included as an option in first-line antiretroviral therapy (ART) for antiretroviral-naïve individuals in treatment guidelines in high-income countries, including the United States and many European countries. Rilpivirine is available in a single-tablet fixed-dose combination, has a favourable tolerability profile and is of relatively low cost. However, rilpivirine has reduced efficacy in patients commencing ART at high viral loads. Therefore, baseline viral load testing is required before commencing rilpivirine, and it is not recommended for patients commencing therapy with a viral load greater than 100 000 copies/mL. Rilpivirine is not included in the treatment regimens recommended by the World Health Organization (WHO), which form the basis of treatment guidelines in many lower- and middle-income countries. Some patients commencing standard first-line regimens experience treatment-limiting toxicity. A low-cost rilpivirine-containing fixed-dose combination would potentially be a useful addition to treatment options available in South Africa and other countries in the region, for patients who do not tolerate standard first-line ART. In this article, we explore the utility of rilpivirine as an option in ART in South Africa and the region in the context of current public-sector regimens. We consider what role rilpivirine might play if first-line therapy moves to a dolutegravir-based regimen, as has already happened in some lower- and middle-income countries, including Botswana, Kenya and Brazil. Finally, we describe emerging evidence for rilpivirine in the prevention of HIV transmission.

BACKGROUND. Kaposi's sarcoma (KS) typically occurs in the setting of immunodeficiency and specifically in the presence of HIV infection, when it is called AIDS-associated KS (AIDS-KS). In spite of impressive gains in the South African (SA) antiretroviral therapy (ART) roll-out programme since 2004, AIDS-KS still causes significant morbidity and mortality, and the treatment of advanced disease can be challenging owing to the centralisation of oncology services and the high incidence of concurrent infections. In 2014, a multidisciplinary AIDS-KS clinic (MKSC) was established at Tygerberg Hospital, Cape Town, with the goal of optimising management of AIDS-KS patients. OBJECTIVES. To report on the characteristics and outcomes of patients seen during the first 6 months after the inception of the MKSC. METHODS. A retrospective observational study was performed of all new cases referred to the MKSC from February to August 2014. RESULTS. Forty-two patients were included in the study. The median age was 34 years (range 20 - 60). Forty-one patients were on ART at time of diagnosis or were initiated by a median of 3 months after diagnosis. The median CD4+ count before diagnosis was 147 cells/uL (range 4 -811). The HIV viral load was undetectable in 22 cases (52.4%). Thirty-eight patients (90.5%) were classified as AIDS Clinical Trials Group (ACTG) poor risk, 10 patients (23.8%) had visceral KS, 14 patients (33.3%) were on tuberculosis (ih) treatment at time of presentation, and 22 patients (52.4%) received oncological therapy in addition to ART. After median follow-up of 25.6 months, 2-year overall survival (OS) was 61.1%. On univariate analysis, factors significantly associated with poor 2-year OS included ACTG SI stage (S = systemic illness), visceral KS, being on ih treatment, and Eastern Cooperative Oncology Group performance status score >2. In the T1 (T = tumour extent) subgroup, receiving chemotherapy was significantly associated with improved 2-year OS. CONCLUSIONS. Advanced AIDS-KS significantly affects young people in the Western Cape Province of SA despite 10 years of ART roll-out. There is a high prevalence of concomitant ih infection that could adversely affect adherence and response to treatment. Despite advanced disease at presentation and palliative treatment intent, survival outcomes are encouraging and seem to be positively affected by the increased use of chemotherapy. A multidisciplinary approach to diagnosis, staging and treatment and the exploration of prognostic indices specific to the sub-Saharan setting would be valuable in designing appropriate treatment algorithms.

Alguns pacientes sob terapêutica antirretroviral (TARV) não obtêm recuperação imune quando a carga viral se torna indetectável. Isto é chamado resposta imunológica e virológica discordante. A prevalência varia entre 8% e 24%. Este estudo descreve sua prevalência e características dos afetados em ambulatório de um centro de cuidados especializados brasileiro. De 934 pacientes sob TARV, 536 tinham carga viral indetectável. A prevalência foi 51/536, ou 9% (Intervalo de Confiança de 95% de 6,6% a 11,4%). Idade mediana no início da TARV foi 37 anos (distância interquartílica - DQ: 31 a 45). Gênero masculino e cor parda predominaram (76,5% e 47,1%, respectivamente). Doenças definidoras de Aids estavam ausentes no início da TARV em 60,8%. Cinquenta e um por cento recebiam inibidores da Protease, 43,2% Efavirenz e 5,8% ambos. Tempo mediano de TARV foi 36 meses (DQ: 17-81). Tratamento irregular foi registrado em 21,6%. TARV havia sido anteriormente modificado em 63% e 15,7% haviam usado mono ou dupla terapêutica. A contagem mediana de CD4 foi 255 células/mm³ (DQ: 200-284). O logaritmo mediano da carga viral antes do TARV foi 4,7 (DQ: 4,5-5,2). Aqueles com resposta discordante não eram diferentes dos pacientes com AIDS em geral, mas houve alta frequência de múltiplos esquemas terapêuticos.

Some patients under antiretroviral therapy (ART) do not reach immune recovery when the viral load becomes undetectable. This is called discordant immunologic and virologic responses. Its prevalence varies between 8% and 24%. This study describes its prevalence and the characteristics of the affected subjects in the outpatient clinic of a Brazilian specialized-care center. Of 934 patients on ART, 536 had undetectable viral loads. Prevalence was 51/536 or 9% (95% confidence interval: 6.6% to 11.4%). Median age at the beginning of ART was 37 years (interquartile range - IQR: 31 to 45). Male gender and mixed race predominated (76.5% and 47.1% respectively). AIDS-defining illnesses were absent at the beginning of ART in 60.8%. Fifty-one percent were taking protease inhibitors, 43.2% Efavirenz and 5.8% both. Median time on ART was 36 months (IQR: 17-81 months). Irregular treatment was recorded for 21.6%. ART had been modified for 63% prior to the study, and 15.7% had used monotherapy or double therapy. Median CD4 count was 255 cells/mm³ (IQR: 200-284). Median viral load before ART was 4.7 log10 copies/mL (IQR: 4.5-5.2). Discordant responders were not different from AIDS patients in general, but there was a high frequency of multiple schedules of treatment.

OBJECTIVES: To examine the uptake of ART among pregnant women referred to an ART service and the associated rates and risk factors for vertical HIV transmission. METHODS: Retrospective analysis of an observational cohort at a community ART clinic in Cape Town. RESULTS: Between 2002 and 2008, 367 treatment-naïve pregnant women accessed the clinic. The median age was 27.5 years, and median gestation at presentation was 28 weeks. The median baseline CD4 count and viral load were 134 cells/µl and 28 282 copies/ml. Two hundred and sixty-five women (72%) commenced ART before giving birth, 73 women (20%) were referred for prevention of mother-to-child transmission therapy (PMTCT), and 29 (8%) received no intervention. Among ART-eligible women, 13% were lost to follow-up. Of those starting ART, median duration of therapy prior to birth was 7.6 weeks (interquartile range (IQR) 4 - 11.9).The HIV transmission rate was 5.1% (95% confidence interval (CI) 2.8 - 9.0%). Factors associated with transmission were advanced maternal WHO disease stage (odds ratio (OR) 9.57, p=0.02), and follow-up viral load above 50 copies/ml (OR 3.64, p=0.03). Each additional week on ART reduced transmission by 20% (p=0.05). There was no HIV transmission among women who received more than 8 weeks' therapy. CONCLUSIONS: The rate of HIV transmission in this study was higher than reported in high-income countries. Prevention of vertical transmission with ART was hindered by women presenting late in pregnancy and with advanced stage of HIV disease. Interventions that facilitate earlier ART commencement and improve programmatic retention of pregnant women are required.

OBJECTIVES: To assess paediatric antiretroviral treatment (ART) outcomes and their associations from a collaborative cohort representing 20% of the South African national treatment programme. DESIGN AND SETTING: Multi-cohort study of 7 public sector paediatric ART programmes in Gauteng, Western Cape and KwaZulu-Natal provinces. SUBJECTS: ART-naïve children (<16 years) who commenced treatment with >3 antiretroviral drugs before March 2008. OUTCOME MEASURES: Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART. RESULTS: The median (interquartile range) age of 6 078 children with 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% being <18 months. Most were severely ill at ART initiation. More than 75% of children were appropriately monitored at 6-monthly intervals with viral load suppression (<400 copies/ml) being 80% or above throughout 36 months of treatment. Mortality and retention in care at 3 years were 7.7% (95% confidence interval 7.0 - 8.6%) and 81.4% (80.1 - 82.6%), respectively. Together with young age, all markers of disease severity (low weight-for-age z-score, high viral load, severe immune suppression, stage 3/4 disease and anaemia) were independently associated with mortality. CONCLUSIONS: Dramatic clinical benefit for children accessing the national ART programme is demonstrated. Higher mortality in infants and those with advanced disease highlights the need for early diagnosis of HIV infection and commencement of ART.