Metabolomic profiling of preterm birth in pregnant women living with HIV.

BACKGROUND: Preterm birth is a leading cause of death in children under the age of five. The risk of preterm birth is increased by maternal HIV infection as well as by certain antiretroviral regimens, leading to a disproportionate burden on low- and medium-income settings where HIV is most prevalent. Despite decades of research, the mechanisms underlying spontaneous preterm birth, particularly in resource limited areas with high HIV infection rates, are still poorly understood and accurate prediction and therapeutic intervention remain elusive. OBJECTIVES: Metabolomics was utilized to identify profiles of preterm birth among pregnant women living with HIV on two different antiretroviral therapy (ART) regimens. METHODS: This pilot study comprised 100 mother-infant dyads prior to antiretroviral initiation, on zidovudine monotherapy or on protease inhibitor-based antiretroviral therapy. Pregnancies that resulted in preterm births were matched 1:1 with controls by gestational age at time of sample collection. Maternal plasma and blood spots at 23-35 weeks gestation and infant dried blood spots at birth, were assayed using an untargeted metabolomics method. Linear regression and random forests classification models were used to identify shared and treatment-specific markers of preterm birth. RESULTS: Classification models for preterm birth achieved accuracies of 95.5%, 95.7%, and 80.7% in the untreated, zidovudine monotherapy, and protease inhibitor-based treatment groups, respectively. Urate, methionine sulfone, cortisone, and 17α-hydroxypregnanolone glucuronide were identified as shared markers of preterm birth. Other compounds including hippurate and N-acetyl-1-methylhistidine were found to be significantly altered in a treatment-specific context. CONCLUSION: This study identified previously known as well as novel metabolomic features of preterm birth in pregnant women living with HIV. Validation of these models in a larger, independent cohort is necessary to ascertain whether they can be utilized to predict preterm birth during a stage of gestation that allows for therapeutic intervention or more effective resource allocation.

Doxycycline post-exposure prophylaxis for sexually transmitted infections in South Africa.

South Africa has a large burden of bacterial sexually transmitted infections (STIs) with high rates among men who have sex with men (MSM). Randomised controlled trials have recently demonstrated high effectiveness of doxycycline post-exposure prophylaxis (PEP) for prevention of bacterial STIs in MSM, with 70% - 85% reductions in Chlamydia trachomatis infection and syphilis, and approximately 50% reduction in Neisseria gonorrhoeae infection. Doxycycline PEP was not demonstrated to be effective in reducing C. trachomatis and N. gonorrhoeae infection among Kenyan cisgender women. Although no worrisome trends in antimicrobial resistance (AMR) were observed in the trials, important concerns remain about doxycycline PEP and AMR development in STIs, other pathogens, commensals, and the microbiome. Tetracycline resistance in N. gonorrhoeae is already widespread in South Africa, but emergence of AMR in other STIs would be concerning. Larger sample sizes of doxycycline PEP users with longer follow-up time are needed to understand the impact that doxycycline PEP may have on AMR at individual and population level. In this opinion article, we weigh the benefits of doxycycline PEP for prevention of bacterial STIs against the existing AMR concerns and data gaps in the South African context. Based on the current evidence, we conclude that it would be reasonable to offer doxycycline PEP to high-risk MSM on a case-by-case basis, provided that it is offered by experienced sexual health clinicians in settings that have access to diagnostic STI testing and ongoing AMR surveillance.

A Single Question on Maternal HIV Status Can Improve Identification of Children Living With HIV in South Africa.

INTRODUCTION: Screening tools to improve identification of children living with HIV (CLHIV) have been validated and used in various settings. The aim of our study was to optimize a screening tool for Primary Healthcare Clinics (PHCs) in South Africa (SA). METHODS: A cross-sectional study was conducted at PHCs in Johannesburg and Mopani Districts, between June 2021 and June 2022. Children 5-14 years of age with HIV negative or unknown status accompanied by their mothers, or appropriate caregivers, were enrolled. Demographic data, responses to the screening tool questions, and HIV test results were captured. Logistic regression modeling was used to optimize an existing 10-item screening tool, and sensitivity, specificity, and number needed to test (NNT) used to choose the final tool. RESULTS: We enrolled 14,147 children in the study, with 62 children testing HIV positive (HIV positivity of 0.4%). The 10-item tool with a single positive response had a sensitivity of 91.9% and specificity of 43.3%. An optimal combination of 5-items with two positive responses had the lowest NNT of 72, 82.3% sensitivity and 74.2% specificity. Maternal HIV status alone, HIV positive or unknown, had a 95.2% sensitivity, 65.0% specificity and NNT of 84. The 1-item tool only would have missed 5% of CLHIV (N = 3) compared with the 5-item tool that missed 18% (n = 11). CONCLUSIONS: A 1-item screening tool asking about maternal HIV status can improve efficiency of testing of children in primary healthcare facilities in SA and improve identification of CLHIV who are not on treatment.

Thermal Debridement in the Management of Low Grade Scapholunate Ligament Tears.

Low grade scapholunate interosseous ligament (SLIL) tears are often managed with mechanical or thermal arthroscopic debridement, although this remains controversial. This study aimed to assess the short-term outcomes of thermal debride- ment of low-grade SLIL tears. Patients with low grade SLIL tears who underwent arthroscopic thermal debridement between 2010 and 2017 were identified and divided into two groups: isolated thermal debridement and concomitant pro- cedures. Patient reported outcomes, wrist range of motion, grip strength, return to work, and baseline activities were evaluated. Twenty-seven patients underwent isolated thermal debridement and 20 underwent concomitant procedures. Pain significantly improved in both groups. Grip strength significantly improved in the concomitant procedure group. There was no significant change in wrist range of motion in either group. Most patients returned to baseline activities. Arthroscopic thermal debridement provides good outcomes in patients with low grade SLIL tears both in isolation and in association with other injuries.

Supporting retention in HIV care through a holistic, patient-centred approach: a qualitative evaluation.

BACKGROUND: HIV is a complex disease which affects different facets (social, economic, physical, emotional and spiral) of an individual's life, making the goals of retention in care and adherence to treatment difficult to achieve. Holistic patient-centred approaches to providing care for people living with HIV bind together economic, social, emotional and physiological aspects and have the potential to improve retention in care and ART adherence. Case management is a holistic, patient-centred approach which is increasingly being implemented in the management of chronic illnesses. METHODS: We conducted a qualitative study based on semi-structured interviews with key informants (retention officers and social auxiliary workers) and patients. A total of 60 patients and 17 KIs (11 retention officers and 6 social auxiliary workers) participated in the study. The study was conducted in Johannesburg District, Gauteng province, South Africa. Key informants (KIs) and patients were drawn from 8 health facilities located in four management clusters of the district. RESULTS: The findings identified facilitators and barriers to adherence and retention in care, and demonstrated that case management offered holistic, patient-centred services which patients considered to be beneficial to their well-being and helped them overcome some of these barriers. The success of case management was driven by its holistic and patient-centred approach, which extended the focus to patients' non-clinical needs which impact on their quality of life. Complex interacting barriers and facilitators at different levels influenced implementation of the model and its outcomes. CONCLUSION: Holistic approaches such as case management have a strong potential to improve retention in care and adherence to ART. HIV is a complex disease which impacts different facets of an individual's life, hence requires holistic care to address all facets. Health systems need to transition towards holistic care to ensure that some patients do not slip through the cracks, improve patient outcomes and efficiency.

Exploring healthcare workers' experiences of managing patients returning to HIV care in Johannesburg, South Africa.

BACKGROUND: Retention of patients in HIV care is a critical barrier to reaching the UNAIDS 90-90-90 goals in South Africa. In January 2019, Anova Health Institute launched a campaign to encourage patients who had interrupted antiretroviral therapy to return to care. The Welcome Back campaign included training of health care workers and implementation of Médecins Sans Frontiers Welcome Services principles. OBJECTIVE: The aim of this study was to explore the experiences of healthcare workers managing patients reinitiating antiretroviral therapy following training, including barriers and facilitators to implementation. METHODS: Data were collected from six clinics. This study consisted of three components: 1) surveys; 2) semi-structured interviews and 3) reflexive feedback sessions. Each component covered staff attitudes and facility management of patients reinitiating antiretroviral therapy. A descriptive analysis was conducted of survey responses. A thematic approach was used to analyze interviews. RESULTS: Thirty-six healthcare workers completed the survey and interview. Following analysis, feedback sessions were conducted with 99 healthcare workers. Twenty-two (61%) participants were lay counsellors. The majority of healthcare workers reported managing patients returning to care appropriately. However, barriers persisted: 9 (25%) responded that patients were sent to the back of the queue and that service providers continued to insist on transfer letters. Twenty-five (69%) responded they had seen/heard other healthcare workers act poorly towards returning patients after training. Many poor behaviours from healthcare workers stemmed from frustration with the clinical flow and their overburdened work environment. Many participants (78%) believed that the Welcome Back approach helped improve client-provider relationships. CONCLUSIONS: The Welcome Back approach supported healthcare workers to improve service provision for patients reinitiating antiretroviral therapy. Further support is needed to help providers consistently deliver services in line with the Welcome Back approach. Institutional level changes are required to implement patient-centred and trust-based models of care.

Risk profile of postnatal women and their babies attending a rural district hospital in South Africa.

Background: Maternal and neonatal mortality remain unacceptably high and inequitably distributed in South Africa, with the postnatal period being a dangerous time for both mother and baby. The aim of this paper is to describe the risk factors for poor postnatal outcomes, including postnatal mental health disorders, in a population of postnatal women and their babies utilising rural district hospital services in Limpopo Province, with a focus on HIV. We also describe health care provider compliance with relevant guidelines. Methods: All women discharged from the postnatal ward of the district hospital who consented to participate were enrolled. A research nurse used a structured questionnaire to collect data about sociodemographic information, pregnancy and pre-existing conditions, complications during labour and birth, pregnancy outcomes and mental health risk factors. Results: The questionnaire was completed for 882 women at the time of discharge. Only 354 (40.2%) of participants had completed secondary education, and 105 (11.9%) reported formal employment. Chronic hypertension was recorded in 20 women (2.3%), with an additional 49 (5.6%) developing a hypertensive disorder during pregnancy. HIV prevalence was 22.8%. 216 women (24.5%) had a mental health risk factor, with 40 reporting more than one (4.5%). Having no income, no antenatal care, having HIV and any hypertensive disorder were significantly associated with a positive mental health risk screen in multivariable analysis. There were 31 stillbirths and early neonatal deaths (3.5%), and 119 babies (13.4%) were born at a low birth weight. Stillbirth or early neonatal death was significantly associated with no antenatal care in multivariable analysis. Conclusions: Women and babies in this study experienced multiple risk factors for poor outcomes in the postpartum period. Postnatal care should be strengthened in order to address the dominant risks to mothers and babies, including socioeconomic challenges, HIV and hypertension, and risks to mental health. Tools to identify mothers and babies at risk of postnatal complications would allow limited resources to be allocated where they are most needed.

High rate of loss to follow-up and virological non-suppression in HIV-infected children on antiretroviral therapy highlights the need to improve quality of care in South Africa.

Provision of high-quality care and ensuring retention of children on antiretroviral therapy (ART) are essential to reduce human immunodeficiency virus (HIV)-associated morbidity and mortality. Virological non-suppression (≥1000 viral copies/ml) is an indication of suboptimal HIV care and support. This retrospective cohort study included ART-naïve children who initiated first-line ART between July 2015 and August 2017 in Johannesburg and rural Mopani district. Of 2739 children started on ART, 29.5% (807/2739) were lost to care at the point of analysis in August 2018. Among retained children, overall virological non-suppression was 30.2% (469/1554). Virological non-suppression was associated with higher loss to care 30.3% (229/755) compared with suppressed children (9.7%, 136/1399, P < 0.001). Receiving treatment in Mopani was associated with virological non-suppression in children under 5 years (adjusted odds ratio (aOR) 1.7 (95% confidence interval (CI) 1.1-2.4), 5-9 years (aOR 1.8 (1.1-3.0)) and 10-14 years (aOR 1.9 (1.2-2.8)). Virological non-suppression was associated with lower CD4 count in children 5-9 years (aOR 2.1 (1.1-4.1)) and 10-14 years (aOR 2.1 (1.2-3.8)). Additional factors included a shorter time on ART (<5 years aOR 1.8-3.7 (1.3-8.2)), and male gender (5-9 years, aOR1.5 (1.01-2.3)), and receiving cotrimoxazole prophylaxis (10-14 years aOR 2.0 (1.2-3.6)). In conclusion, virological non-suppression is a factor of subsequent programme loss in both regions, and factors affecting the quality of care need to be addressed to achieve the third UNAIDS 90 in paediatric HIV.

Mother-to-child transmission of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis in HIV-infected pregnant women in South Africa.

BACKGROUND: Sexually transmitted infections (STIs) can be transmitted from mother to neonate. We determined the frequency of mother-to-child transmission (MTCT) of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis to the newborn nasopharynx. METHODS: This study was nested in a cohort study of etiologic testing versus syndromic management for STIs among pregnant women living with human immunodeficiency virus in South Africa. Mothers were tested for STIs using the GeneXpert platform within 60 days after delivery. Nasopharyngeal swabs were obtained from newborns of mothers with a positive STI test; these were then tested by Xpert® on the same day based on the maternal STI diagnosis. RESULTS: We tested nasopharyngeal swabs from 85 STI-exposed newborns; 74 (87%) were tested within 2 weeks after birth (median five; range 2-12 days). MTCT frequency of any STI was 30/74 (41%); 43% (23/53) for C. trachomatis, 29% (2/7) for N. gonorrhoeae, and 24% (6/25) for T. vaginalis. Also, 4/11 (36%) swabs obtained between 14 and 60 days after delivery tested positive for STI. CONCLUSIONS: There was a high frequency of MTCT of STIs to the nasopharynx of newborns in our setting. The impact of nasopharyngeal colonization and the benefits of STI testing on newborn health remain to be determined.

Single-Dose Azithromycin for Genital Lymphogranuloma Venereum Biovar Chlamydia trachomatis Infection in HIV-Infected Women in South Africa: An Observational Study.

ABSTRACT: We conducted an observational study of lymphogranuloma venereum (LGV) biovar Chlamydia trachomatis infection in HIV-infected women in South Africa. The LGV biovar was detected in vaginal specimens of 17 (20%) of 85 women with C. trachomatis infection; 29% were symptomatic. All cases were negative for the LGV biovar after single-dose azithromycin.

Increases in HIV status disclosure and sexual communication between South African men who have sex with men and their partners following use of HIV self-testing kits.

Availability of HIV self-testing may increase HIV testing frequency among men who have sex with men (MSM). It is unclear, however, if self-testing may impact HIV-related sexual behaviors among MSM, including HIV status disclosure and condom use. We conducted a mixed methods analysis of changes in HIV-related behaviors after HIV self-testing introduction, using data from 110 MSM participating in a feasibility and acceptability study of HIV self-testing in Mpumalanga Province, South Africa. We found increased HIV status disclosure from study participants to sexual partners after HIV self-testing introduction, from 61.8% at baseline to 75.5% at 6-month follow-up (p = 0.04), but decreased condom use with female partners (p = 0.03). Qualitative interviews reveal that some participants used test results to inform condom use. Distribution of self-testing kits can improve mutual disclosure, but should be accompanied by information stressing that the tests may not detect early HIV infections or other sexually transmitted infections.

Defining gaps in pre-exposure prophylaxis delivery for pregnant and post-partum women in high-burden settings using an implementation science framework.

Pregnancy is a high-risk period for HIV acquisition in African women, and pregnant women who become acutely infected with HIV account for up to a third of vertical HIV transmission cases in African settings. To protect women and eliminate vertical transmission, WHO recommends offering oral pre-exposure prophylaxis (PrEP) based on tenofovir to HIV-negative pregnant and post-partum women with a substantial risk of HIV acquisition. PrEP implementation for pregnant and post-partum women lags behind implementation for other high-risk populations. Unique considerations for PrEP implementation arise during pregnancy and post partum, including the integration of provider training with clinical delivery and monitoring of PrEP exposure and outcomes within existing maternal health systems, yet scarce implementation data are available to generate evidence in this context.

Implementation of a PMTCT programme in a high HIV prevalence setting in Johannesburg, South Africa: 2002-2015.

BACKGROUND: Great strides have been made in decreasing paediatric human immunodeficiency virus (HIV) infections, especially in sub-Saharan Africa. In South Africa, new paediatric HIV infections decreased by 84% between 2009 and 2015. This achievement is a result of a strong political will and the rapid evolution of the country's prevention of mother-to-child transmission (PMTCT) guidelines. OBJECTIVES: In this paper we report on the implementation of a large PMTCT programme in Soweto, South Africa. METHODS: We reviewed routinely collected PMTCT data from 13 healthcare facilities, for the period 2002-2015. Antiretroviral therapy (ART) coverage among pregnant women living with HIV (PWLHIV) and the mother-to-child transmission (MTCT) rate at early infant diagnosis were evaluated. RESULTS: In total, 360 751 pregnant women attended the facilities during the review period, and the HIV prevalence remained high throughout at around 30%. The proportion of PWLHIV presenting with a known HIV status increased from 14.3% in 2009 when the indicator was first collected to 45% in 2015, p < 0.001. In 2006, less than 10% of the PWLHIV were initiated on ART, increasing to 88% by 2011. The MTCT rate decreased from 6.9% in 2007 to under 1% from 2013 to 2015, p < 0.001. CONCLUSION: The achievements in decreasing paediatric HIV infections have been hailed as one of the greatest public health achievements of our times. While there are inherent limitations with using routinely collected aggregate data, the Soweto data reflect progress made in the implementation of PMTCT programmes in South Africa. Progress with PMTCT has, however, not been accompanied by a decline in HIV prevalence among pregnant women.

Same-day antiretroviral therapy initiation for HIV-infected adults in South Africa: Analysis of routine data.

Same-day initiation (SDI) of antiretroviral therapy (ART) has been recommended to improve ART programme outcomes in South Africa since August 2017. This study assessed implementation of SDI over time in two South African districts, describing the characteristics of same-day initiators and evaluating the impact of SDI on retention in ART care. Routine data were analysed for HIV-infected adults who were newly initiating ART in Johannesburg or Mopani Districts between October 2017 and June 2018. Characteristics of same-day ART initiators were compared to later initiators, and losses to follow-up (LTFU) to six months were assessed using Kaplan Meier survival analysis and multivariate logistic regression. The dataset comprised 32 290 records (29 964 from Johannesburg and 2 326 from Mopani). The overall rate of SDI was 40.4% (n = 13 038), increasing from 30.3% in October 2017 to 54.2% in June 2018. Same-day ART initiators were younger, more likely to be female and presented with less advanced clinical disease than those initiating treatment at later times following diagnosis (p<0.001 for all). SDI was associated with disengagement from care: LTFU was 30.1% in the SDI group compared to 22.4%, 19.8% and 21.9% among clients initiating ART 1-7 days, 8-21 days and ≥22 days after HIV diagnosis, respectively (p<0.001). LTFU was significantly more likely among clients in Johannesburg versus Mopani (adjusted odds ratio (aOR) = 1.43, p<0.001) and among same-day versus later initiators (aOR = 1.45, p<0.001), while increasing age reduced LTFU (aOR = 0.97, p<0.001). In conclusion, SDI has increased over time as per national guidelines, but there is serious concern regarding the reduced rate of retention among same-day initiators. Nevertheless, SDI may result in a net programmatic benefit provided that interventions are implemented to support client readiness for treatment and ongoing engagement in ART care, particularly among younger adults in large ART programmes such as Johannesburg.

Contextual factors affecting the integration of community health workers into the health system in Limpopo Province, South Africa.

BACKGROUND: Community health workers (CHWs) are an essential cadre in the health systems of many low- and middle-income countries. These workers provide a wide variety of services and are key to ongoing processes of task shifting within human immunodeficiency virus programmes in particular. Ward-based outreach teams (WBOTs) are South Africa's latest iteration of the CHW programme and have been introduced as part of the National Department of Health's Primary Health Care Re-engineering programme. METHODS: In order to assess the perceived effectiveness of the WBOTs in supporting the ongoing rollout of antiretroviral therapy, tuberculosis care and patient support, we conducted a qualitative investigation focusing on the perceived successes and challenges of the programme among CHWs, community leaders, healthcare workers and community members in the Mopani district, Limpopo province, South Africa. RESULTS: The CHW programme operates across these contexts, each associated with its own set of challenges and opportunities. CONCLUSIONS: While these challenges may be interrelated, a contextual analysis provides a useful means of understanding the programme's implementation as part of ongoing decision-making processes.

CD4 testing after initiation of antiretroviral therapy: Analysis of routine data from the South African HIV programme.

BACKGROUND: People living with HIV (PLHIV) who have low CD4 counts require advanced clinical care (ACC) to minimise morbidity and mortality risk. These patients include immunological non-responders (INRs) with low CD4 counts despite a suppressed viral load. OBJECTIVES: To determine the proportion of patients with low CD4 counts after antiretroviral therapy (ART) initiation and to describe INRs within that group. METHODS: Routine Three Interlinked Electronic Registers.Net (TIER.Net) data from four South African districts were analysed for adult PLHIV on ART > 12 months. Immunological non-responders were defined as patients on ART > 4 years who were virally suppressed (viral load < 1000 copies/mL) with a CD4 count ≤ 350 cell/mm3. RESULTS: Baseline CD4 was recorded for 80.9% of the 869 571 patients newly initiating ART, with 37.2% of those starting ART since 2017 having baseline counts ≤ 200 cells/mm3. Amongst all 1 178 190 patients on ART, only 46.5% had a CD4 test after ART initiation and of these, 14.3% had CD4 ≤ 200 cells/mm3. This proportion was highest amongst patients on ART ≤ 2 years (19.7%) (p < 0.001). Amongst virally suppressed patients, 20.0% were INRs. Immunological non-response was significantly more likely amongst patients on second-line ART (adjusted odds ratio [aOR] 1.79), those aged 35-45 and ≥ 45 years (aOR 1.15 and 1.50, respectively), males (aOR 2.28) and patients with confirmed TB (aOR 2.49), and was significantly less likely in cases with higher baseline CD4 count (aOR 0.35). CONCLUSION: CD4 testing subsequent to ART initiation is poorly implemented and there is a notable proportion of patients with low CD4 counts. Guidelines regarding CD4 testing and ACC need to be more widely implemented to identify patients with low CD4 counts and improve their outcomes.

Linked dual-class HIV resistance mutations are associated with treatment failure.

We hypothesized that HIV-1 with dual-class but not single-class drug resistance mutations linked on the same viral genome, present in the virus population before initiation of antiretroviral therapy (ART), would be associated with failure of ART to suppress viremia. To test this hypothesis, we utilized an ultrasensitive single-genome sequencing assay that detects rare HIV-1 variants with linked drug resistance mutations (DRMs). A case (ART failure) control (nonfailure) study was designed to assess whether linkage of DRMs in pre-ART plasma samples was associated with treatment outcome in the nevirapine/tenofovir/emtricitabine arm of the AIDS Clinical Trials Group A5208/Optimal Combined Therapy After Nevirapine Exposure (OCTANE) Trial 1 among women who had received prior single-dose nevirapine. Ultrasensitive single-genome sequencing revealed a significant association between pre-ART HIV variants with DRMs to 2 drug classes linked on the same genome (dual class) and failure of combination ART with 3 drugs to suppress viremia. In contrast, linked, single-class DRMs were not associated with ART failure. We conclude that linked dual-class DRMs present before the initiation of ART are associated with ART failure, whereas linked single-class DRMs are not.

Baseline CD4 and mortality trends in the South African human immunodeficiency virus programme: Analysis of routine data.

BACKGROUND: Despite widespread availability of antiretroviral therapy (ART) in South Africa, there remains a considerable burden of human immunodeficiency virus (HIV)-related morbidity and mortality. OBJECTIVES: To describe ART initiation and outcome trends over time, with a focus on clients presenting with advanced HIV-infection, so as to identify interventions to reduce morbidity and mortality. METHODS: Routine TIER.Net data from HIV-infected adults who had a documented baseline CD4 count and were newly initiating ART in Johannesburg or Mopani districts from 2004 to 2017 were analysed. Trends in baseline CD4 count and 5-year mortality were investigated and the population initiating ART with CD4 < 200 cells/mm3 was described. RESULTS: The Johannesburg and Mopani data sets comprised 203 131 and 101 814 records, respectively. Although median CD4 count increased over time, the proportion of initiations at CD4 < 200 cells/mm3 in 2017 remained high (Johannesburg 39%, Mopani 35%). Mortality was significantly increased among clients with CD4 < 200 compared to those with higher baseline counts (p < 0.001). Even though mortality among clients with low CD4 declined over time, likely because of improved drug regimens, in 2016-2017 mortality was still significantly increased among these clients (p < 0.001). Delivery of cotrimoxazole prophylaxis to clients with low CD4 declined over time to < 30% in 2017 and was associated with clinical stage. Presentation with CD4 < 200 cells/mm3 was associated with older age, male gender and hospitalisation. CONCLUSION: A concerningly large proportion of South Africans still initiate ART at low CD4 counts. This is associated with increased mortality and requires targeted interventions to improve delivery of prophylactic regimens and early engagement in care.

Time to viral rebound and safety after antiretroviral treatment interruption in postpartum women compared with men.

OBJECTIVE(S): The short-term safety of treatment interruptions, a necessary part of cure studies, is not well established, particularly in women. We explored viral rebound kinetics and safety in a group of postpartum women discontinuing ART and compared results to men in historical interruption trials. DESIGN: Prospective evaluation of time to virologic rebound. METHODS: One thousand and seventy-six asymptomatic, virally suppressed, postpartum women living with HIV enrolled in the PROMISE trial with baseline CD4 cell counts at least 350 cells/µl underwent antiretroviral treatment (ART) discontinuation. Proportion with virologic suppression at weeks 4 and 12 were compared with participants in ACTG treatment interruption trials (91% male population). RESULTS: In PROMISE, using interval censored methods, the estimated median time to HIV viral rebound was 2 weeks. An estimated 6% of women would remain virally suppressed at 30 weeks. Of those who had viral rebound by 30 weeks (N = 993), less than 4% experienced grade 3 or higher laboratory events, and 1% experienced WHO stage 2 or higher clinical events. Overall, less than 1% of participants progressed from WHO Stage 1 to Stage 2 or higher after discontinuation of ART, and 3.9% experienced a decline in CD4 cell count to less than 350 cells/µl or local treatment guidelines. A significantly higher proportion of women in PROMISE (25.4%) were virologically suppressed (<400 copies/ml) at 12 weeks compared with ACTG NWCS 371 participants (6.4%). CONCLUSION: Temporary treatment interruptions in healthy, HIV-infected women with high CD4 cell counts can be well tolerated. Potential sex differences need to be considered in cure studies examining time to virologic rebound.