Mother-child dyads living with HIV in the Western Cape, South Africa: Undetectable = Undetectable?

Mother-child pairs may separate during early life, yet the health impacts thereof are unclear. We explored the patterns and impact of separation among women living with HIV (WLHIV) and their children in South Africa. WLHIV who had initiated antiretroviral therapy (ART) during pregnancy received HIV viral load (VL) testing and completed a timeline questionnaire of mother-child separation since delivery at 3-5years post-partum. Health care usage was abstracted from routine medical records. We examined associations between separation and (a) maternal health outcomes (engagement in HIV care and HIV viral suppression, [VS]) and (b) child health outcomes (post-breastfeeding HIV testing and immunisation completion), using logistic regression. Of 346 mother-child pairs (median maternal age at antenatal ART initiation, 28years), 24% were ever separated (median time to first separation 20months, interquartile range [IQR] 9, 31). Most separated children were living with their grandmothers (65/83, 78%). Mothers who ever separated were younger, and more likely to be employed, and to reside in informal housing than those who never separated. Any separation reduced the odds of VS≤50 copies/mL at four years post-partum (odds ratio 0.57; 95% CI 0.34-0.93); associations were similar for VL≤1000 copies/mL and maternal engagement in care. No association was found between separation and child confirmatory HIV testing or immunisation completion. In this setting, mother-child separation is common in the first four years of life and appears associated with suboptimal maternal outcomes. Further research is required to understand the drivers and implications of mother-child separation.

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To investigate whether an unrecognised diagnosis of tuberculosis (TB) at the start of antiretroviral therapy (ART) influences subsequent CD4+ T cell (CD4) count recovery in an urban HIV clinic in Uganda. In a retrospective cohort study, a multivariable polynomial mixed effects model was used to estimate CD4 recovery in the first 96 weeks of ART in two groups of patients: prevalent TB (started ART while on TB treatment), unrecognised TB (developed TB within 6 months after start ART). Included were 511 patients with a median baseline CD4 count of 57 cells/mm(3) (interquartile range: 22-130), of whom 368 (72%) had prevalent TB and 143 (28%) had unrecognised TB. Compared with prevalent TB, unrecognised TB was associated with lower CD4 count recovery at 96 weeks: -22.3 cells/mm(3) (95% confidence interval -43.2 to -1.5, P = 0.036). These estimates were adjusted for gender, age, baseline CD4 count and the use of zidovudine-based regimen. Unrecognised TB at the time of ART initiation resulted in impaired CD4 recovery compared with TB treated before ART initiation. More vigilant screening with more sensitive and rapid TB diagnostics prior to ART initiation is needed to decrease the risk of ART-associated TB and sub-optimal immune reconstitution.

British HIV Association guidelines for the management of HIV infection in pregnant women 2012 (2014 interim review).

SummaryBackgroundThe length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.MethodsThe UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.ResultsOf the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.InterpretationA substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.FundingUK Medical Research Council.

IntroductionMost people achieve and maintain viral load (VL) suppression on first-line antiretroviral therapy (ART) but for a minority this does not happen. It is unclear whether those who have maintained VL suppression for several years will be able to continue to do so, or if rates of VL failure – due to poor adherence, ART interruption and/or resistance – remain at appreciable levels.MethodsEligible participants were ART-naïve and started treatment after 1st January 2000, with ≥3 antiretrovirals and ≥9 months follow-up. VL failure was defined as failure to achieve VL suppression (≤50 copies/mL) by 9 months on ART or a single VL >200 copies/mL after 9 months after start of ART. Kaplan-Meier estimates were used to examine the cumulative probability of experiencing a VL >200 copies/mL over time, irrespective of treatment interruption (Figure 1). Follow-up was censored at last VL assessment but not at treatment interruption. In a sensitivity analysis, VL failure was instead defined as two consecutive VL >1000 copies/mL.ResultsA total of 13,556 participants were included. Median (IQR) age at start of ART was 37 (32–43), median follow-up 4.1 (2.3–6.7) years, pre-ART VL 71,400 (17,400–221,900) copies/mL and pre-ART CD4 count 204 (110–290) cells/mm3. Fifty-one percent were white, 71% male and 50% MSM. Of which, 5,351 (39%) participants experienced a VL >200 copies/mL. In sub-groups of participants the proportion experiencing a VL >200 copies/mL by one year after start of ART were: <50 years 22%, ≥50 years 17%, men 20%, women 26%, MSM 19%, black heterosexuals 23%, white heterosexuals 26% and other 23%. The median time to VL >200 copies/ml was 8 years. In sensitivity analyses based on 12,811 participants, 4274 (33%) experienced two consecutive VL >1000 copies/mL. Table 1 presents the rate of experiencing a VL >200 copies/mL (two consecutive VL >1000 copies/mL) by time since start of ART. The rate of VL >200 copies/mL declines over time, from 30 per 100 person-years after up to two years after ART, to two per 100 person-years after up to 11.5 years after ART. A sum of 2,047 (15%) participants stopped ART at some point (10, 14 and 17% had stopped ART by 1, 3, and 5 years, respectively).ConclusionsAlthough resistance will often not be present and, even if present, several drug options will likely remain, first occurrence of VL > 200 copies/mL after having attained viral suppression continues to occur after 10 years on ART.

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. 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. 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). 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.

Objectives:South Africa has made remarkable progress in increasing the coverage of antiretroviral therapy (ART) among pregnant women; however, viral suppression among pregnant women receiving ART is reported to be low. Access to routine viral load testing is crucial to identify women with unsuppressed viral load early in pregnancy and to provide timely intervention to improve viral suppression. This study aimed to determine the coverage of maternal viral load monitoring nationally, focusing on viral load testing, documentation of viral load test results, and viral suppression (viral load < 50 copies/mL). At the time of this study, the first-line regimen for women initiating ART during pregnancy was non-nucleoside reverse transcriptase (NNRTI)-based regimen.Methods:Between 1 October and 15 November 2019, a cross-sectional survey was conducted among 15- to 49-year-old pregnant women attending antenatal care in 1589 nationally representative public health facilities. Data on ART status, viral load testing and viral load test results were extracted from medical records. Logistic regression was used to examine factors associated with coverage of viral load testing.Results:Of 8112 participants eligible for viral load testing, 81.7% received viral load testing, and 94.1% of the viral load test results were documented in the medical records. Of those who had viral load test results documented, 74.1% were virally suppressed. Women initiated on ART during pregnancy and who received ART for three months had lower coverage of viral load testing (73%) and viral suppression (56.8%) compared with women initiated on ART before pregnancy (82.8% and 76.1%, respectively). Initiating ART during pregnancy rather than before pregnancy was associated with a lower likelihood of receiving a viral load test during pregnancy (adjusted odds ratio = 1.6, 95% confidence interval: 1.4–1.8).Conclusions:Viral load result documentation was high; viral load testing could be improved especially among women initiating ART during pregnancy. The low viral suppression among women who initiated ART during pregnancy despite receiving ART for three months highlights the importance of enhanced adherence counselling during pregnancy. Our finding supports the WHO recommendation that a Dolutegravir-containing regimen be the preferred regimen for women who are newly initiating ART during pregnancy for more rapid viral suppression.

Data on tuberculosis (TB) incidence and risk factors among children living with HIV (CLHIV) in the universal ART era are limited. We analyzed routinely collected data on TB diagnoses for CLHIV age ≤5 years, born 2018-2022, in the Westen Cape, South Africa. We examined factors associated with TB diagnosis, with death and loss to follow-up as competing events. Among 2219 CLHIV, 30% were diagnosed with HIV at birth. Median follow-up from birth was 38 months [interquartile range (IQR: 24-50); 90% started antiretroviral therapy (ART). TB was diagnosed in 28% of CLHIV (n = 626/2219); 62% were first diagnosed before/within 3 months of ART start ("TB before ART") and 38% >3 months after ART start ("TB after ART"). Of those with "TB before ART" (n = 390), median age at HIV diagnosis was 13 months (IQR: 6-22); median time between HIV and TB diagnoses was 5 days (IQR: 0-31). "TB before ART" was associated with older age at HIV diagnosis and advanced/severe immunodeficiency. Of those with "TB after ART" (n = 258), median age at HIV diagnosis was 2 months (IQR: 0-8) and median time from ART start to TB diagnosis was 12 months (IQR: 7-21). "TB after ART" was associated with increased viral load and advanced/severe immunosuppression (time updated). Overall, 5% (n = 112/2219) of CLHIV died, 36% of whom were diagnosed with TB (median time from TB diagnosis to death: 58 days; IQR: 17-191). Young CLHIV in this setting have high TB-associated morbidity and mortality. Efforts to improve early HIV and TB diagnosis, viral suppression, and TB preventive therapy are needed.

IntroductionThere are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.MethodsThe Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.ResultsOf 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.ConclusionsWe found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

IntroductionThe World Health Organization (WHO) recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa.MethodsWe analysed data from 14 HIV treatment programmes in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in 2005 to 2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3) or failing to suppress viral replication (>1000 HIV‐RNA copies/mL) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex.ResultsAmong 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017; the probability declined by 14% each year (odds ratio (OR) 0.86; 95% CI 0.86 to 0.86). Frequency of CD4 testing also declined. The percentage starting ART with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018; each year the probability declined by 20% (OR 0.80; 95% CI 0.80 to 0.81). VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested, but fewer than 2% were tested in the other four countries. The probability of VL testing after ART start increased only modestly each year (OR 1.06; 95% CI 1.05 to 1.06). The percentage with unsuppressed VL was 8.6%. There was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99 to 1.01).ConclusionsCD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub‐Saharan Africa.

BackgroundSustained viral suppression is a critical measure of the effectiveness of antiretroviral therapy (ART) and a vital component in achieving the UNAIDS "95-95-95" strategy, which seeks to ensure that 95% of people with HIV on ART attain viral load suppression by 2030. In the Kyrgyz Republic, where HIV incidence continues to rise, an increasing number of people are on ART. Understanding the factors associated with viral suppression is important for interrupting HIV transmission.Table 1.General characteristics of the study population of people living with HIV on antiretroviral treatment in Kyrgyzstan, 2023.Table 2.Factors associated with viral load suppression among people living with HIV on antiretroviral treatment in Kyrgyzstan, 2023RR: relative risk from bivariable Poisson regression estimators.aRR: adjusted relative risk from multivariable Poisson regression including all variables listed in the tableMethodsWe conducted a retrospective cohort study among adults >18 years old with HIV in Kyrgyzstan. Participants included people initiating or reinitiating ART from June 2021 to June 2023 and who were on ART for at least 6 months. We performed logistic regression to identify factors associated with viral load suppression, defined as >200 copies/ml based on the most recent viral load test.ResultsAmong 377 participants, 95% achieved HIV viral suppression and 85% had undetectable viral load (≤40 copies/ml) (Table 1). Participants were mostly male (60%), 30-49 years old (60%), and self-employed (49%). All were on a dolutegravir containing ART. The proportion of those with viral suppression was below 90% for people who were re-initiating ART, with advanced HIV disease at diagnosis, who started ART more than 3 months after their HIV diagnosis, who injected drugs in last 12 months, and with monthly or unclear frequency of ART appointments. One-quarter of people self-reported an interruption in ART. People without skipped ART doses had higher likelihood of being virally suppressed (adjusted relative risk: 1.11 (95% confidence interval: 1.03-1.19) (Table 2).ConclusionThe results of the study show a high level of viral suppression and Kyrgyzstan is achieving the target of 95% viral load suppression among PLHIV, even though one-quarter of participants reported skipping ART doses. Understanding the frequency and reasons for missed doses is important to maintain high viral suppression.DisclosuresAll Authors: No reported disclosures

Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs when treatment fails to suppress a person's VL and is associated with decreased survival and increased HIV transmission. The objective of this study was to evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients currently in care on first-line ART for ≥ 6 months attending South African public healthcare facilities. We analysed electronic medical records of ART patients with a VL result on record who started ART between January 2004 and April 2016 from 271 public health facilities. We present descriptive and multivariable logistic regression for unsuppressed VL at last visit using a priori variables. We included 244,370 patients (69% female) on first-line ART in April 2016 for ≥ 6 months. Median age at ART start was 33 years (7% were < 15 years old). Median duration on ART was 3.7 years. Adjusting for other variables, factors associated with having an unsuppressed VL at the most recent visit among patients in care included: (1) < 15 years old at ART start (adjusted odds ratio [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR = 1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95% CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI = 1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved viral suppression, though men, youth/adolescents, patients with prior ART exposure, those with short duration of ART, and patients on TB treatment had increased odds of not achieving viral suppression. There is a need to develop and evaluate targeted interventions for ART patients in care who are at high risk of unsuppressed VL.

Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

the Human Immunodeficiency Virus (HIV) remains a global health concern, with South Africa among the hardest hit countries. Viral suppression in HIV patients is a positive treatment outcome when monitoring progress and using antiretrovirals (ART). Despite the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 strategy which focuses on monitoring viral suppression, unsuppressed viral loads keep persisting because of several factors. The study sought to determine viral load suppression and contributing factors among adult patients on first-line ART in Ekurhuleni District, South Africa. the study reviewed 379 patient files of adult patients on first-line ART between April and June 2018. Standardized tools were used to collect sociodemographic and clinical data. Descriptive data was analyzed using frequency tabulations and percentages, and multivariable logistic regression was used to identify factors associated with viral load suppression. the study included 379 patient records. Mean age; DS of 38.9 years with standard deviation at 10.1. The prevalence of viral load suppression at 12 months was 75.2% (n=285). Female participants had higher suppression rates 77.7% (n=188) than males 70.8% (n=97), received pre-ART counseling 73.1% (n=277) as well as no history of tuberculosis 92.4% (n=350). Being female with (aOR=7.29, 95% CI: 1.02 - 52.26; p=0.04) and having completed a six-month viral load assessment (aOR=1.85, 95% CI: 1.00 - 3.41; p=0.04) were independently associated with higher odds of having a suppressed viral load. However, being referred for adherence (aOR=0.61, 95% CI: 0.37 - 0.99; p=0.05) and having a previous history of ART exposure (aOR=0.29, 95% CI 0.10 - 0.77; p=0.01) were independently associated with lower odds of having a suppressed viral load. a higher suppression rate among female patients, suggests that more targeted interventions should be facilitated among HIV-positive male patients linkage to care and initiated on ART. Exposing the patient to a few enhanced support programs hinders progress toward reducing nonadherence, lack of awareness, and inadequate knowledge about the benefits of achieving viral suppression among people living with HIV.