Vital Signs: Progress Toward Eliminating HIV as a Global Public Health Threat Through Scale-Up of Antiretroviral Therapy and Health System Strengthening Supported by the U.S. President's Emergency Plan for AIDS Relief - Worldwide, 2004-2022.

Introduction: In 2004, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), with CDC as a major U.S. government implementing agency, began providing HIV antiretroviral therapy (ART) worldwide. Through suppression of HIV viral load, effective ART reduces morbidity and mortality among persons with HIV infection and prevents vertical and sexual transmission. Methods: To describe program impact, data were analyzed from all PEPFAR programs and from six countries that have conducted nationally representative Population-based HIV Impact Assessment (PHIA) surveys, including PEPFAR programmatic data on the number of persons with HIV infection receiving PEPFAR-supported ART (2004-2022), rates of viral load coverage (the proportion of eligible persons with HIV infection who received a viral load test) and viral load suppression (proportion of persons who received a viral load test with <1,000 HIV copies per mL of blood) (2015-2022), and population viral load suppression rates in six countries that had two PHIA surveys conducted during 2015-2021. To assess health system strengthening, data on workforce and laboratory systems were analyzed. Results: By September 2022, approximately 20 million persons with HIV infection in 54 countries were receiving PEPFAR-supported ART (62% CDC-supported); this number increased 300-fold from the 66,550 reported in September 2004. During 2015-2022, viral load coverage more than tripled, from 24% to 80%, and viral load suppression increased from 80% to 95%. Despite increases in viral load suppression rates and health system strengthening investments, variability exists in viral load coverage among some subpopulations (children aged <10 years, males, pregnant women, men who have sex with men [MSM], persons in prisons and other closed settings [persons in prisons], and transgender persons) and in viral load suppression among other subpopulations (pregnant and breastfeeding women, persons in prisons, and persons aged <20 years). Conclusions and implications for public health practice: Since 2004, PEPFAR has scaled up effective ART to approximately 20 million persons with HIV infection in 54 countries. To eliminate HIV as a global public health threat, achievements must be sustained and expanded to reach all subpopulations. CDC and PEPFAR remain committed to tackling HIV while strengthening public health systems and global health security.

Group antenatal care for improving retention of adolescent and young pregnant women living with HIV in Kenya.

BACKGROUND: Pregnant and breastfeeding adolescents and young women living with HIV (AYWLH) have lower retention in prevention of mother-to-child transmission (PMTCT) services compared to older women. METHODS: We evaluated a differentiated service model for pregnant and postnatal AYWLH at seven health facilities in western Kenya aimed at improving retention in antiretroviral treatment (ART) services. All pregnant AYWLH < 25 years presenting for antenatal care (ANC) were invited to participate in group ANC visits including self-care and peer-led support sessions conducted by health facility nurses per national guidelines. ART register data were used to assess loss to follow-up (LTFU) among newly-enrolled pregnant adolescent (< 20 years) and young women (20-24 years) living with HIV starting ART in the pre-period (January-December 2016) and post-period (during implementation; December 2017-January 2019). Poisson regression models compared LTFU incidence rate ratios (IRR) in the first six months after PMTCT enrollment and risk ratios compared uptake of six week testing for HIV-exposed infants (HEI) between the pre- and post-periods. RESULTS: In the pre-period, 223 (63.2%) of 353 pregnant AYWLH newly enrolled in ANC had ART data, while 320 (71.1%) of 450 in the post-period had ART data (p = 0.02). A higher proportion of women in the post-period (62.8%) had known HIV-positive status at first ANC visit compared to 49.3% in the pre-period (p < 0.001). Among pregnant AYWLH < 20 years, the incidence rate of LTFU in the first six months after enrollment in ANC services declined from 2.36 per 100 person months (95%CI 1.06-5.25) in the pre-period to 1.41 per 100 person months (95%CI 0.53-3.77) in the post-period. In both univariable and multivariable analysis, AYWLH < 20 years in the post-period were almost 40% less likely to be LTFU compared to the pre-period, although this finding did not meet the threshold for statistical significance (adjusted incidence rate ratio 0.62, 95%CI 0.38-1.01, p = 0.057). Testing for HEI was 10% higher overall in the post-period (adjusted risk ratio 1.10, 95%CI 1.01-1.21, p = 0.04). CONCLUSIONS: Interventions are urgently needed to improve outcomes among pregnant and postnatal AYWLH. We observed a trend towards increased retention among pregnant adolescents during our intervention and a statistically significant increase in uptake of six week HEI testing.

Survival and HIV-Free Survival Among Children Aged ≤3 Years - Eight Sub-Saharan African Countries, 2015-2017.

Although mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) is preventable through antiretroviral treatment (ART) during pregnancy and postpartum, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates that 160,000 new HIV infections occurred among children in 2018 (1). Child survival and HIV-free survival rates* are standard measures of progress toward eliminating MTCT† (2). Nationally representative Population-based HIV Impact Assessment (PHIA)§ survey data, pooled from eight sub-Saharan African countries¶ were used to calculate survival probability among children aged ≤3 years by maternal HIV status during pregnancy and HIV-free survival probability among children aged ≤3 years born to women with HIV infection, stratified by maternal ART** status during pregnancy. Survival probability was significantly lower among children born to women with HIV infection (94.7%) than among those born to women without HIV infection (97.6%). HIV-free survival probability of children born to women with HIV infection differed significantly by the timing of initiation of maternal ART: 93.0% among children whose mothers received ART before pregnancy, 87.8% among those whose mothers initiated ART during pregnancy, and 53.4% among children whose mothers did not receive ART during pregnancy. Focusing on prevention of HIV acquisition and, among women of reproductive age with HIV infection, on early diagnosis of HIV infection and ART initiation when applicable, especially before pregnancy, can improve child survival and HIV-free survival.

Caregiver perspectives on TB case-finding and HIV clinical services for children diagnosed with TB in Tanzania.

Caregivers of children with tuberculosis (TB) and HIV play a critical role in seeking healthcare for their children. To assess the perspectives of caregivers of pediatric TB patients, we conducted 76 in-depth interviews at 10 TB clinics in 5 districts of Tanzania in March 2016. We assessed how the child received their TB diagnosis, the decision-making process around testing the child for HIV, and the process of linking the child to HIV treatment in the event of an HIV diagnosis. Caregivers suspected TB due to cases in their family, or the child being ill and not improving. Most caregivers noted delays before confirmation of a TB diagnosis and having to visit multiple facilities before a diagnosis. Once diagnosed, some caregivers reported challenges administering TB medications due to lack of pediatric formulations. Reasons for accepting HIV testing included recurrent illness and HIV symptoms, history of HIV in the family, and recommendation of the clinical provider. Caregivers described a relatively seamless process for linking their child to HIV treatment, highlighting the success of TB/HIV integration efforts. The multiple clinic visits required prior to TB diagnosis suggests the need for additional training and sensitization of healthcare workers and better TB diagnostic tools.

Addressing Vulnerable Population Needs in the Last Mile to the elimination of mother to child transmission of HIV: (Re)Claiming the HIV Response for Female Sex Workers and Their Children.

As countries strive to eliminate mother-to-child transmission of HIV, female sex workers (FSW) and their children still face barriers to accessing these essential services. Data on FSW uptake of HIV and reproductive health services before, during, and after pregnancy reveal inadequate service utilization. Stigma encountered by FSW in healthcare settings may contribute to low uptake of HIV testing, antiretroviral therapy (ART), and other prevention of mother-to-child HIV transmission (PMTCT) services. Coordination between community-based FSW and facility-based PMTCT programs can facilitate successful linkage of pregnant FSW to antenatal services to support PMTCT efforts. We offer a way forward to reach 90-90-90 targets for FSW and their families and eliminate mother-to-child transmission of HIV.

Bringing women's voices to PMTCT CARE: adapting CARE's Community Score Card© to engage women living with HIV to build quality health systems in Malawi.

BACKGROUND: Coverage of prevention of mother-to-child transmission of HIV (PMTCT) services has expanded rapidly but approaches to ensure service delivery is patient-centered have not always kept pace. To better understand how the inclusion of women living with HIV in a collective, quality improvement process could address persistent gaps, we adapted a social accountability approach, CARE's Community Score Card© (CSC), to the PMTCT context. The CSC process generates perception-based score cards and facilitates regular quality improvement dialogues between service users and service providers. METHODS: Fifteen indicators were generated by PMTCT service users and providers as part of the CSC process. These indicators were scored by each population during three sequential cycles of the CSC process which culminates in a sharing of scores in a collective meeting followed by action planning. We aggregated these scores across facilities and analyzed the differences in first and last scorings to understand perceived improvements over the course of the project (z-test comparing the significance of two proportions; one-tailed p-value ≤ .05). Data were collected over 12 months from September 2017 to August 2018. RESULTS: Fourteen of the fifteen indicators improved over the course of this project, with eight showing statistically significant improvement. Out of the indicators that showed statistically significant improvement, the majority fell within the control of local communities, local health facilities, or service providers (7 out of 8) and were related to patient or user experience and support from families and community members (6 out of 8). From first to last cycle, scores from service users' and service providers' perspectives converged. At the first scoring cycle, four indicators exhibited statistically significant differences (p-value ≤ .05) between service users and service providers. At the final cycle there were no statistically significant differences between the scores of these two groups. CONCLUSIONS: By creating an opportunity for mothers living with HIV, health service providers, communities, and local government officials to jointly identify issues and implement solutions, the CSC contributed to improvements in the perceived quality of PMTCT services. The success of this model highlights the feasibility and importance of involving people living with HIV in quality improvement and assurance efforts. TRIAL REGISTRATION: Trial registration: ClincalTrials.gov NCT04372667 retrospectively registered on May 1st 2020.

What will it take for the Global Plan priority countries in Sub-Saharan Africa to eliminate mother-to-child transmission of HIV?

BACKGROUND: The 2016 'Start Free, Stay Free, AIDS Free' global agenda, builds on the 2011-2015 'Global Plan'. It prioritises 22 countries where 90% of the world's HIV-positive pregnant women live and aims to eliminate vertical  transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries. METHODS: A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation's building blocks to strengthen health systems, van Olmen's Health System Dynamics framework and Baral's socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate). RESULTS: EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (p<0.001); in simple linear regression it is 53% protective against percent MTCT. In contrast, SEM demonstrated that the case rate was driven by the number of HIV exposed infants (HEI) i.e. maternal HIV prevalence (p<0.001). In linear regression models, ART access alone explains only 17% of the case rate while HEI alone explains 81% of the case rate. In multiple regression, HEI and ART access accounts for 83% of the case rate, with HEI making the most contribution (coef. infant HIV exposure=82.8, 95% CI: 64.6, 101.1, p<0.001 vs coef. ART access=-3.0, 95% CI: -6.2, 0.3, p=0.074). CONCLUSION: Reducing infant HIV exposure, is critical to reducing the paediatric HIV case rate; increasing ART access is critical to reduce percent MTCT. Additionally, our study of four validated countries underscores the importance of contact tracing, strengthening programme monitoring, leadership and governance, as these are potentially-modifiable factors.

Symptom screening for active tuberculosis in pregnant women living with HIV.

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: To assess the accuracy of the four-symptom screen (cough, fever, night sweats, or weight loss) for identifying active TB in pregnant PLHIV who are screened in an outpatient or community setting. To investigate potential sources of heterogeneity of the accuracy of the four-symptom screen between studies including: ART status, CD4 cell count, gestational age, pregnancy stage (pregnancy vs. postpartum), screening test definition of cough (any cough vs. cough greater than 2 weeks).To describe the accuracy of single symptoms included within the four-symptom screen, additioal symptoms or symptom combinations, for identifying active TB in pregnant PLHIV. For example, additional symptoms may include failure to gain weight or fatigue.

Screening in Maternity to Ascertain Tuberculosis Status (SMATS) study.

BACKGROUND: Diagnosis of tuberculosis is difficult among pregnant women because the signs and symptoms of the disease, such as fatigue, shortness of breath, sweating, cough, and mild fever are similar to some manifestations of pregnancy. It is particularly challenging among HIV-infected women as symptoms are often masked or atypical. Currently, WHO recommends a standard four-symptom screening tool for pregnant and lactating women. There is evidence from South Africa that this screening tool (which, despite complex symptomology in this population, recommends identification of patients with weight loss, fever, current cough and night sweats), may be missing true active TB cases. However there exist several laboratory and clinical procedures that have the potential to improve the sensitivity and specificity of this screening tool. METHODS: This study will evaluate the sensitivity and specificity of the current TB screening tool for pregnant and lactating women, both HIV positive and negative. We will also assess several different enhanced screening algorithm using LAM, IGRA, TST and chest radiography and clinical/laboratory procedures and tests. The study will use a cross-sectional analytical study design involving pregnant and lactating women up to six months post-delivery attending antenatal or postnatal care, respectively in one of three selected public health units in Swaziland. Participants will be consecutively enrolled and will be in one of four groups of interest: HIV infected pregnant women, non-HIV infected pregnant women, HIV infected lactating women and non-HIV infected lactating women. DISCUSSION: We expect in conducting all procedures on all participants regardless of result of the symptom screening we may experience a high refusal rate. However, this risk will be mitigated by the long data collection period of five or more months.

Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel.

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.

More Frequent HIV Viral Load Testing With Point-Of-Care Tests Detects Elevated Viral Load Earlier in Postpartum HIV-Positive Women in a Randomized Controlled Trial in Two Clinics in Johannesburg, South Africa.

BACKGROUND: Elevated maternal HIV viral load (VL) increases vertical transmission risk for breastfeeding children. This randomized controlled trial in Johannesburg primarily evaluated whether 3-monthly point-of-care testing, with laboratory-based standard-of-care testing (arm 2), compared with 6-monthly laboratory-based VL testing (arm 1) in postpartum women living with HIV receiving first-line tenofovir-emtricitabine-efavirenz antiretroviral treatment improved VL suppression, factors associated with nonsuppression, and drug resistance in those with virologic failure. METHODS: Mother-child pairs were enrolled July 2018-April 2019 at the child's 6/10/14-week clinic visit. Women were randomized 1:1 to arm 1 or 2. Trained staff performed point-of-care VL testing using the Cepheid's Xpert HIV-1 VL assay. We fitted a generalized linear mixed model with VL suppression (<50 copies/mL (cps/mL) and <1000 cps/mL) at enrollment and 6, 12, and 18 months postpartum as the outcome and indicator variables for time, study site, study arm, and interaction variables. The final model tested for a difference by study arm, pooling across time points. RESULTS: Of 405 women enrolled (204 arm 1 and 201 arm 2), 249 (61%) remained in follow-up through 18 months. There was no difference in VL suppression between arms at 6, 12, or 18 months. VL suppression rate (<50 cps/mL) at 18 months was 64.8% in arm 1 and 63.0% in arm 2 (P = 0.27). On bivariate analysis, there was an association with late antenatal booking and being in arm 2 for nonsuppressed VL, but no significant association with breastfeeding. HIV drug resistance was found in 12 of 23 participants (52.2%). CONCLUSION: We found no significant difference in VL suppression with more frequent VL testing in postpartum women living with HIV receiving first-line efavirenz-based antiretroviral treatment.

Characteristics of multidrug-resistant tuberculosis in Namibia.

BACKGROUND: To describe the epidemiology and possible risk factors for the development of multidrug-resistant tuberculosis (MDR-TB) in Namibia. METHODS: Using medical records and patient questionnaires, we conducted a case-control study among patients diagnosed with TB between January 2007 and March 2009. Cases were defined as patients with laboratory-confirmed MDR-TB; controls had laboratory-confirmed drug-susceptible TB or were being treated with WHO Category I or Category II treatment regimens. RESULTS: We enrolled 117 MDR-TB cases and 251 TB controls, of which 100% and 2% were laboratory-confirmed, respectively. Among cases, 97% (113/117) had been treated for TB before the current episode compared with 46% (115/251) of controls (odds ratio [OR] 28.7, 95% confidence interval [CI] 10.3-80.5). Cases were significantly more likely to have been previously hospitalized (OR 1.9, 95% CI 1.1-3.5) and to have had a household member with MDR-TB (OR 5.1, 95% CI 2.1-12.5). These associations remained significant when separately controlled for being currently hospitalized or HIV-infection. CONCLUSIONS: MDR-TB was associated with previous treatment for TB, previous hospitalization, and having had a household member with MDR-TB, suggesting that TB control practices have been inadequate. Strengthening basic TB control practices, including expanding laboratory confirmation, directly observed therapy, and infection control, are critical to the prevention of MDR-TB.

Enhanced Integration of TB Services in Reproductive Maternal Newborn and Child Health (RMNCH) Settings in Eswatini.

Tuberculosis (TB) primarily affects women during their reproductive years and contributes to maternal mortality and poor pregnancy outcomes. For pregnant women living with HIV (WLHIV), TB is the leading cause of non-obstetric maternal mortality, and pregnant WLHIV with TB are at increased risk of transmitting both TB and HIV to their infants. TB diagnosis among pregnant women, particularly WLHIV, remains challenging, and TB preventive treatment (TPT) coverage among pregnant WLHIV is limited. This project aimed to strengthen integrated TB and reproductive, maternal, neonatal and child health (RMNCH) services in Eswatini to improve screening and treatment for TB disease, TPT uptake and completion among women receiving RMNCH services. The project was conducted from April-December 2017 at four health facilities in Eswatini and introduced enhanced monitoring tools and on-site technical support in RMNCH services. We present data on TB case finding among women, and TPT coverage and completion among eligible WLHIV. A questionnaire (S1 Appendix) measured healthcare provider perspectives on the project after three months of project implementation, including feasibility of scaling-up integrated TB and RMNCH services. A total of 5,724 women (HIV-negative or WLHIV) were screened for active TB disease while attending RMNCH services; 53 (0.9%) were identified with presumptive TB, of whom 37 (70%) were evaluated for TB disease and 6 (0.1% of those screened) were diagnosed with TB. Among 1,950 WLHIV who screened negative for TB, 848 (43%) initiated TPT and 462 (54%) completed. Forty-three healthcare providers completed the questionnaire, and overall were highly supportive of integrated TB and RMNCH services. Integration of TB/HIV services in RMNCH settings was feasible and ensured high TB screening coverage among women of reproductive age, however, symptom screening identified few TB cases, and further studies should explore various screening algorithms and diagnostics that optimize case finding in this population. Interventions should focus on working with healthcare providers and patients to improve TPT initiation and completion rates.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.

Approaches to transitioning women into and out of prevention of mother-to-child transmission of HIV services for continued ART: a systematic review.

INTRODUCTION: Women living with HIV are required to transition into the prevention of mother-to-child transmission of HIV (PMTCT) services when they become pregnant and back to ART services after delivery. Transition can be a vulnerable time when many women are lost from HIV care yet there is little guidance on the optimal transition approaches to ensure continuity of care. We reviewed the available evidence on existing approaches to transitioning women into and out of PMTCT, outcomes following transition and factors influencing successful transition. METHODS: We searched PubMed and SCOPUS, as well as abstracts from international HIV-focused meetings, from January 2006 to July 2020. Studies were included that examined three points of transition: pregnant women already on ART into PMTCT (transition 1), pregnant women living with HIV not yet on ART into treatment services (transition 2) and postpartum women from PMTCT into general ART services after delivery (transition 3). Results were grouped and reported as descriptions of transition approach, comparison of outcomes following transition and factors influencing successful transition. RESULTS & DISCUSSION: Out of 1809 abstracts located, 36 studies (39 papers) were included in this review. Three studies included transition 1, 26 transition 2 and 17 transition 3. Approaches to transition were described in 26 studies and could be grouped into the provision of information at the point of transition (n = 8), strengthened communication or linkage of data between services (n = 4), use of transition navigators (n = 12), and combination approaches (n = 4). Few studies were designed to directly assess transition and only nine compared outcomes between transition approaches, with substantial heterogeneity in study design, setting and outcomes. Four themes were identified in 25 studies reporting on factors influencing successful transition: fear, knowledge and preparedness, clinic characteristics and the transition requirements and process. CONCLUSIONS: This review highlights that, despite the need for women to transition into and out of PMTCT services for continued ART in many settings, there is very limited evidence on optimal transition approaches. Ongoing operational research is required to identify sustainable and acceptable transition approaches and service delivery models that support continuity of HIV care during and after pregnancy.

Improving retention in antenatal and postnatal care: a systematic review of evidence to inform strategies for adolescents and young women living with HIV.

INTRODUCTION: Young pregnant and postpartum women living with HIV (WLHIV) are at high risk of poor outcomes in prevention of mother-to-child transmission services. The aim of this systematic review was to collate evidence on strategies to improve retention in antenatal and/or postpartum care in this population. We also conducted a secondary review of strategies to increase attendance at antenatal care (ANC) and/or facility delivery among pregnant adolescents, regardless of HIV status, to identify approaches that could be adapted for adolescents and young WLHIV. METHODS: Selected databases were searched on 1 December 2020, for studies published between January 2006 and November 2020, with screening and data abstraction by two independent reviewers. We identified papers that reported age-disaggregated results for adolescents and young WLHIV aged <25 years at the full-text review stage. For the secondary search, we included studies among female adolescents aged 10 to 19 years. RESULTS AND DISCUSSION: Of 37 papers examining approaches to increase retention among pregnant and postpartum WLHIV, only two reported age-disaggregated results: one showed that integrated care during the postpartum period increased retention in HIV care among women aged 18 to 24 years; and another showed that a lay counsellor-led combination intervention did not reduce attrition among women aged 16 to 24 years; one further study noted that age did not modify the effectiveness of a combination intervention. Mobile health technologies, enhanced support, active follow-up and tracing and integrated services were commonly examined as standalone interventions or as part of combination approaches, with mixed evidence for each strategy. Of 10 papers identified in the secondary search, adolescent-focused services and continuity of care with the same provider appeared to be effective in improving attendance at ANC and/or facility delivery, while home visits and group ANC had mixed results. CONCLUSIONS: This review highlights the lack of evidence regarding effective strategies to improve retention in antenatal and/or postpartum care among adolescents and young WLHIV specifically, as well as a distinct lack of age-disaggregated results in studies examining retention interventions for pregnant WLHIV of all ages. Identifying and prioritizing approaches to improve retention of adolescents and young WLHIV are critical for improving maternal and child health.

Uninterrupted HIV treatment for women: Policies and practices for care transitions during pregnancy and breastfeeding in Côte d'Ivoire, Lesotho and Malawi.

Transitions between services for continued antiretroviral treatment (ART) during and after pregnancy are a commonly overlooked aspect of the HIV care cascade, but ineffective transitions can lead to poor health outcomes for women and their children. In this qualitative study, we conducted interviews with 15 key stakeholders from Ministries of Health along with PEPFAR-supported and other in-country non-governmental organizations actively engaged in national programming for adult HIV care and prevention of mother-to-child-transmission of HIV (PMTCT) services in Côte d'Ivoire, Lesotho and Malawi. We aimed to understand perspectives regarding transitions into and out of PMTCT services for continued ART. Thematic analysis revealed that, although transitions of care are necessary and a potential point of loss from ART care in all three countries, there is a lack of clear guidance on transition approach and no formal way of monitoring transition between services. Several opportunities were identified to monitor and strengthen transitions of care for continued ART along the PMTCT cascade.

Associations of Sociodemographic and Clinical Factors with Late Presentation for Early Infant HIV Diagnosis (EID) Services in Kenya.

BACKGROUND: Understanding the missed opportunities in early infant HIV testing within the PMTCT program is essential to address any gaps. The study set out to describe the clinical and sociodemographic characteristics of the infants presenting late for early infant diagnosis in Kenya. METHODS: We abstracted routinely collected clinical and sociodemographic characteristics, in a cross-sectional study, on all HIV-infected infants with a positive polymerase chain reaction (PCR) test from 1,346 President's Emergency Plan for AIDS Relief (PEPFAR) supported health facilities for the period October 2016 to September 2018. We used multivariate logistic regression to examine the association of sociodemographic and clinical characteristics with late (>2 months after birth) presentation for infant HIV testing. RESULTS: Of the 4,011 HIV-infected infants identified, the median infant age at HIV diagnosis was 3 months [interquartile range (IQR), 1-16 months], and two-thirds [2,669 (66.5%)] presented late for infant HIV testing. Factors that were associated with late presentation for infant testing were: maternal ANC non-attendance, adjusted odds ratio (aOR) 1.41 (95% confidence interval (CI) 1.18 -1.69); new maternal HIV diagnosis, aOR 1.45, (95%CI 1.24 -1.7); and lack of maternal antiretroviral therapy(ART), aOR 1.94, (95% CI 1.64 - 2.30). There was a high likelihood of identifying HIV-infected infants among infants who presented for medical services in the outpatient setting (aOR 18.9; 95% CI 10.2 - 34.9) and inpatient setting (aOR 12.2; 95% CI 6.23-23.9) compared to the infants who presented late in maternity. CONCLUSION AND GLOBAL HEALTH IMPLICATIONS: Gaps in early infant HIV testing suggest the need to increase maternal pre-pregnancy HIV diagnosis, timely antenatal care, early infant diagnosis services, early identification of mothers who seroconvert during pregnancy or breastfeeding and improved HIV screening in outpatient and inpatient settings. Early referral from the community and access to health facilities should be strengthened by the implementation of national PMTCT guidelines.