HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape,South Africa

Introduction

There 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.

Methods

The 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.

Results

Of 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.

Conclusions

We 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.

     

Partner testing with HIV self-test distribution by Ugandan pregnant women living with HIV: a randomized trial

Introduction

Secondary distribution of HIV self-tests (HIVST) by HIV-negative pregnant women to male partners increases men's testing rates. We examined whether this strategy promotes male partner testing for pregnant women living with HIV (PWLHIV).

Methods

We conducted an open-label individually randomized trial in Kampala, Uganda, in which PWLHIV ≥18 years who reported a partner of unknown HIV status were randomized 2:1 to secondary distribution of HIVST for male partner(s) or standard-of-care (SOC; invitation letter to male partner for fast-track testing). Women were followed until 12 months post-partum. Male partners were offered confirmatory HIV testing and facilitated linkage to antiretroviral treatment (ART) or oral pre-exposure prophylaxis (PrEP). Using intention-to-treat analysis, primary outcomes were male partner testing at the clinic and initiation on PrEP or ART evaluated through 12 months post-partum (ClinicalTrials.gov, NCT03484533).

Results

From November 2018 to March 2020, 500 PWLHIV were enrolled with a median age of 27 years (interquartile range [IQR] 23–30); 332 were randomized to HIVST and 168 to SOC with 437 PWLHIV (87.4%) completing 12 months follow-up post-partum. Of 236 male partners who tested at the clinic and enrolled (47.2%), their median age was 31 years (IQR 27–36), 45 (88.3%) men with HIV started ART and 113 (61.1%) HIV-negative men started PrEP. There was no intervention effect on male partner testing (hazard ratio [HR] 1.04; 95% confidence interval [CI]: 0.79–1.37) or time to ART or PrEP initiation (HR 0.96; 95% CI: 0.69–1.33). Two male partners and two infants acquired HIV for an incidence of 0.99 per 100 person-years (95% CI: 0.12–3.58) and 1.46 per 100 person-years (95% CI: 0.18%–5.28%), respectively. Social harms related to study participation were experienced by six women (HIVST = 5, SOC = 1).

Conclusions

Almost half of the partners of Ugandan PWLHIV tested for HIV with similar HIV testing rates and linkage to ART or PrEP among the secondary distribution of HIVST and SOC arms. Although half of men became aware of their HIV serostatus and linked to services, additional strategies to reach male partners of women in antenatal care are needed to increase HIV testing and linkage to services among men.     

Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy

Antiretroviral therapy (ART) in people living with human immunodeficiency virus (HIV) is associated with bone loss, but data are limited in lactation, when physiological bone mineral mobilization is occurring. This research charted changes in areal bone mineral density (aBMD) during and after lactation in Ugandan women with HIV (WWH) initiated onto ART in pregnancy, compared to women without HIV (REF). One-hundred WWH on tenofovir-based ART and 100 REF were enrolled in pregnancy. Lumbar spine (LS), total hip (TH), and whole-body-less-head (WBLH) aBMD were measured by dual-energy X-ray absorptiometry (DXA) at 2, 14, and 26 weeks of lactation, and at 3 months postlactation. The primary outcome was the difference between groups in mean percent change in LS aBMD between 2 and 14 weeks. Statistical analysis was performed in hierarchical repeated measures ANOVA models that corrected for multiple testing. Median age was 23.4 (IQR, 21.0 to 26.8) years. WWH had lower body weight. aBMD decreased in both groups during lactation, but WWH had greater decreases at TH (2-to-26 weeks: WWH [n = 63] −5.9% [95% CI, −6.4 to −5.4] versus REF [n = 64] −4.3% [95% CI, −4.8 to −3.8]; group*time point interaction p = .008). Decreases in LS aBMD were similar in WWH and REF (2-to-26 weeks: −2.0% [95% CI, −2.5 to −1.5]), although there was a tendency toward a smaller decrease in WWH between 2 and 14 weeks (WWH [n = 77] −1.8% [95% CI, −2.2 to −1.4] versus REF [n = 69] −2.9% [95% CI, −3.3 to −2.5]; group*time point interaction p = .08). Postlactation, LS aBMD was higher relative to week 2 in both groups. TH and WBLH aBMD did not return to week 2 values in WWH but did in REF (TH postlactation versus week 2: WWH [n = 61] −3.1% [95% CI, −3.6 to −2.6]; REF [n = 29] +0.1% [95% CI, −0.9 to +1.1]). These data show accentuated bone loss during lactation and only partial skeletal recovery by 3 months postlactation in Ugandan WWH on tenofovir-based ART. Studies are ongoing to understand longer-term consequences for bone health. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

People living with HIV travel farther to access healthcare: a population-based geographic analysis from rural Uganda

Introduction

The availability of specialized HIV services is limited in rural areas of sub-Saharan Africa where the need is the greatest. Where HIV services are available, people living with HIV (PLHIV) must overcome large geographic, economic and social barriers to access healthcare. The objective of this study was to understand the unique barriers PLHIV face when accessing healthcare compared with those not living with HIV in a rural area of sub-Saharan Africa with limited availability of healthcare infrastructure.

Methods

We conducted a population-based cross-sectional study of 447 heads of household on Bugala Island, Uganda. Multiple linear regression models were used to compare travel time, cost and distance to access healthcare, and log binomial models were used to test for associations between HIV status and access to nearby health services.

Results

PLHIV travelled an additional 1.9 km (95% CI (0.6, 3.2 km), p=0.004) to access healthcare compared with those not living with HIV, and they were 56% less likely to access healthcare at the nearest health facility to their residence, so long as that facility lacked antiretroviral therapy (ART) services (aRR=0.44, 95% CI (0.24 to 0.83), p=0.011). We found no evidence that PLHIV travelled further for care if the nearest facility supplies ART services (aRR=0.95, 95% CI (0.86 to 1.05), p=0.328). Among those who reported uptake of care at one of two facilities on the island that provides ART (81% of PLHIV and 68% of HIV-negative individuals), PLHIV tended to seek care at a higher tiered facility that provides ART, even when this facility was not their closest facility (30% of PLHIV travelled further than the closest ART facility compared with 16% of HIV-negative individuals), and travelled an additional 2.2 km (p=0.001) to access that facility, relative to HIV-negative individuals (aRR=1.91, 95% CI (1.00 to 3.65), p=0.05). Among PLHIV, residential distance was associated with access to facilities providing ART (RR=0.78, 95% CI (0.61 to 0.99), p=0.044, comparing residential distances of 3–5 km to 0–2 km; RR=0.71, 95% CI (0.58 to 0.87), p=0.001, comparing residential distances of 6–10 km to 0–2 km).

Conclusions

PLHIV travel longer distances for care, a phenomenon that may be driven by both the limited availability of specialized HIV services and preference for higher tiered facilities.     

Decrease in sexual risk behaviours after early initiation of antiretroviral therapy: a 24‐month prospective study in Côte d'Ivoire

Introduction

Whether early antiretroviral therapy (ART) initiation could impact sexual risk behaviours remains to be documented. We aimed to investigate changes in sexual behaviours within the 24 months following an early versus standard ART initiation in HIV-positive adults with high CD4 counts.

Methods

We used data from a prospective behavioural study nested in a randomized controlled trial of early ART (Temprano-ANRS12136). Time trends in sexual behaviours from enrolment in the trial (M0) to 12-month (M12) and 24-month (M24) visits were measured and compared, using Generalized Estimating Equations models, between participants randomly assigned either to initiate ART immediately (early ART) or to defer ART initiation until on-going WHO starting criteria are met (standard ART). Indicators of sexual behaviours included 1) sexual activity in the past year, 2) multiple partnership in the past year, 3) unprotected sex at last intercourse and 4) risky sex (i.e. unprotected sex with a partner of HIV negative/unknown status) at last intercourse.

Results

Analyses included 1952 participants (975 with early ART and 977 with standard ART; overall median baseline CD4 count: 469/mm³). Among participants with early ART, significant decreases were found between M0 and M24 in sexual activity (Odds Ratio [OR] 0.72, 95% Confidence Interval [95% CI] 0.57–0.92), multiple partnership (OR 0.57, 95% CI 0.41–0.79), unprotected sex (OR 0.59, 95% CI 0.47–0.75) and risky sex (OR 0.58, 95% CI 0.45–0.76). Among participants with standard ART, sexual behaviours showed similar trends over time. These decreases mostly occurred within the 12 months following enrolment in the trial in both groups and prior to ART initiation in participants with standard ART. For unprotected sex and risky sex, decreases were or tended to be more pronounced among patients reporting that their last sexual partner was non-cohabiting.

Conclusions

In these sub-Saharan adults with high CD4 counts, entry into HIV care, rather than ART initiation, resulted in decreased sexual activity and risky sexual behaviours. We did not observe any evidence of a risk compensation phenomenon associated with early ART initiation. These results illustrate the potential behavioural preventive effect of early entry into care, which goes hand in hand with early ART initiation.     

Closer to 90–90–90. The cascade of care after 10 years of ART scale-up in rural Malawi: a population study

Introduction

The antiretroviral therapy (ART) programme supported by Médecins Sans Frontières in the rural Malawian district of Chiradzulu was one of the first in sub-Saharan Africa to scale up ART delivery in 2002. After more than a decade of continuous involvement, we conducted a population survey to evaluate the cascade of care, including population viral load, in the district.

Methods

A cross-sectional household-based survey was conducted between February and May 2013. Using a multistage cluster sampling method, we recruited all individuals aged 15 to 59 years living in 4125 randomly selected households. Each consenting individual was interviewed and tested for HIV at home. All participants who tested positive had their CD4 count and viral load measured. The LAg-Avidity assay was used to distinguish recent from long-term infections. Viral suppression was defined as a viral load below 1000 copies/mL.

Results

Of 8271 individuals eligible for the study, 7269 agreed to participate and were tested for HIV (94.1% inclusion for women and 80.3% for men). Overall HIV prevalence and incidence were 17.0% (95% CI 16.1 to 17.9) and 0.39 new cases per 100 person-years (95% CI 0.0 to 0.77), respectively. Coverage at the other steps along the HIV care cascade was as follows: 76.7% (95% CI 74.4 to 79.1) had been previously diagnosed, 71.2% (95% CI 68.6 to 73.6) were under care and 65.8% (95% CI 62.8 to 68.2) were receiving ART. Finally, the proportion of participants who were HIV positive with a viral load ≤1000 copies/mL reached 61.8% (95% CI 59.0 to 64.5).

Conclusions

This study demonstrates that a high level of population viral suppression and low incidence can be achieved in high HIV prevalence and resource-limited settings.     

Diagnostic accuracy of a point-of-care urine tenofovir assay,and associations with HIV viraemia and drug resistance among people receiving dolutegravir and efavirenz-based antiretroviral therapy

Introduction

Novel point-of-care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout.

Methods

We conducted a cross-sectional evaluation among PLHIV receiving first-line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point-of-care immunoassay to detect urine TFV compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS). We evaluated the association between point-of-care urine TFV results and self-reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir-based ART.

Results

Between August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34–45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC-MS/MS were 96.1% (95% CI 90.0−98.8) and 95.2% (75.3−100.0), respectively. Urine TFV results were associated with short (p<0.001) and medium-term (p = 0.036) self-reported adherence. Overall, 44/124 (35.5%) had viraemia, which was associated with undetectable TFV in those receiving efavirenz (OR 6.01, 1.27−39.0, p = 0.014) and dolutegravir (OR 25.7, 4.20−294.8, p<0.001). However, in those with viraemia while receiving efavirenz, 8/27 (29.6%) had undetectable urine TFV, compared to 11/17 (64.7%) of those receiving dolutegravir. Drug resistance was detected in 23/27 (85.2%) of those receiving efavirenz and only 1/16 (6.3%) of those receiving dolutegravir. There was no association between urine TFV results and drug resistance.

Conclusions

Among PLHIV receiving ART, a rapid urine TFV immunoassay can be used to accurately monitor urine TFV levels compared to the gold standard of LC-MS/MS. Undetectable point-of-care urine TFV results were associated with viraemia, particularly among people receiving dolutegravir.

Trial registration

Pan-African Clinical Trials Registry: PACTR202001785886049.     

Implementation of antiretroviral therapy guidelines for under-five children in Tanzania: translating recommendations into practice

Introduction

Paediatric antiretroviral therapy (ART) guidelines have been updated several times in recent years. We assessed implementation of ART guidelines among under-five children to inform the transition to universal paediatric ART in Tanzania.

Methods

We conducted a retrospective cohort analysis of infants (0 to 11 months) and children (12 to 59 months) enrolled between 2010 and 2012 using routinely collected data. Infants and children were initiated on ART according to the 2008 World Health Organization (WHO) recommendations/2009 Tanzania guidelines (universal ART for infants). Cumulative ART initiation incidence and correlates of ART initiation were examined using competing risk methods accounting for attrition (death or loss to follow-up). Kaplan-Meier methods and Cox regression models were used to examine attrition on ART and its correlates.

Results

A total of 1679 children were enrolled at 69 clinics: 469 (28%) infants and 1210 (74%) children. Infant cumulative ART initiation incidence was 59.6, 71.3 and 78.0% at one, three and six months of follow-up. Infants were more likely to start ART if enrolled in 2012 [adjusted sub-hazard ratio (AsHR)=2.2, 95% confidence interval (CI): 1.7 to 2.8] or 2011 (AsHR=1.8, 95% CI: 1.4 to 2.3) compared to 2010; they were more likely to start ART from prevention of mother-to-child HIV transmission (AsHR=1.6, 95% CI: 1.3 to 2.1) and inpatient wards (AsHR=1.5, 95% CI: 1.2 to 2.0) versus being enrolled from voluntary counselling and testing centres. Attrition at 12 months on ART was 33.9% and was more likely among infants with WHO Stage 4 [adjusted hazard ratio (AHR)=3.1. 95% CI: 1.8 to 5.2] and severe malnutrition (AHR=1.4, 95% CI: 1.0 to 1.9).Among 599 children eligible for ART at enrolment, cumulative ART initiation incidence was 51.8, 68.6 and 76.1% at one, three, and six months. Children were more likely to start ART if enrolled in 2012 (AsHR=1.8, 95% CI: 1.4 to 2.3) or 2011 (AsHR=1.5, 95% CI: 1.2 to 1.8) compared to 2010; they were more likely to start ART at primary health facilities (AsHR=1.5, 95% CI: 1.1 to 2.0) and less likely at urban facilities (AsHR=0.6, 95% CI: 0.5 to 0.9) and facilities without CD4 testing on site (AsHR=0.7, 95% CI: 0.5 to 0.9). Attrition at 12 months on ART was 23.1% and was more likely with severe malnutrition (AHR=1.8, 95% CI: 1.1 to 3.0), WHO Stage 4 (AHR=3.0, 95% CI: 1.0 to 8.5) and outpatient enrolees (AHR=1.7, 95% CI: 1.1 to 2.7).

Conclusions

Our findings suggest the gradual adoption of guidelines over calendar time. Interventions to expedite ART initiation and support retention on ART are needed.     

Feasibility and acceptability of mobile phone short message service as a support for patients receiving antiretroviral therapy in rural Uganda: a cross-sectional study

Introduction

Mobile phone technologies have been promoted to improve adherence to antiretroviral therapy (ART). We studied the receptiveness of patients in a rural Ugandan setting to the use of short messaging service (SMS) communication for such purposes.

Methods

We performed a cross-sectional analysis measuring mobile phone ownership and literacy amongst patients of The AIDS Support Organisation (TASO) in Jinja, Uganda. We performed bivariate and multivariate logistic regression analyses to examine associations between explanatory variables and a composite outcome of being literate and having a mobile phone.

Results

From June 2012 to August 2013, we enrolled 895 participants, of whom 684 (76%) were female. The median age was 44 years. A total of 576 (63%) were both literate and mobile phone users. Of these, 91% (527/ 576) responded favourably to the potential use of SMS for health communication, while only 38.9% (124/319) of others were favourable to the idea (p<0.001). A lower proportion of literate mobile phone users reported optimal adherence to ART (86.4% vs. 90.6%; p=0.007). Male participants (AOR=2.81; 95% CI 1.83–4.30), sub-optimal adherence (AOR=1.76; 95% CI 1.12–2.77), those with waged or salaried employment (AOR=2.35; 95% CI 1.23–4.49), crafts/trade work (AOR=2.38; 95% CI 1.11–5.12), or involved in petty trade (AOR=1.85; 95% CI 1.09–3.13) (in comparison to those with no income) were more likely to report mobile phone ownership and literacy.

Conclusions

In a rural Ugandan setting, we found that over 60% of patients could potentially benefit from a mobile phone-based ART adherence support. However, support for such an intervention was lower for other patients.     

Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

Introduction

Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America.

Methods

HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts.

Results

The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57).

Conclusions

HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation.     

Cross-sectional HIV and HCV cascades of care across the regions of Ukraine between 2019 and 2020: findings from the CARE cohort

Introduction

Eastern Europe is facing major HIV and hepatitis C (HCV) epidemics, with many people living with HIV (PLHIV) and HIV/HCV coinfection living in Ukraine. Despite the previous progress towards care quality improvement, the ongoing war in Ukraine is disrupting HIV and HCV care.

Methods

We described an HIV cascade of care (CoC) in PLHIV from two clinical sites and an HCV CoC for anti-HCV-positive PLHIV from six sites in Ukraine, enrolled in the CARE cohort between 1 January 2019 and 1 June 2020. The cross-sectional HIV CoC and HCV CoC are described at study enrolment.

Results

Of 1028 PLHIV, 1014 (98.6%, 95% confidence interval [CI] 97.7–99.3) were on antiretroviral therapy (ART), and 876 (86.4% of those on ART, 95% CI 84.1–88.4) were virologically suppressed. Of 894 participants on ART >6 months, 90.8% (95% CI 88.7–92.6) were virologically suppressed (HIV-RNA <200 copies/ml). Of 2040 anti-HCV-positive PLHIV, 417 (20.4%, 95% CI 18.7–22.3) were ever tested for HCV-RNA prior to enrolment, ranging from 4.9% to 54.4% across sites, and 13.5% were currently HCV-RNA positive. One hundred and eighteen persons (7.3% of ever chronically infected) had received HCV treatment, and 25 persons (1.6% of ever chronically infected) were cured, with variations across sites (0%–7.5%). The site diagnosing 54.4% of people with chronic HCV was the only one providing free RNA testing for all anti-HCV-positive persons, while the intra-country differences in treatment coverage were driven by the number of available direct-acting antiviral (DAA) courses.

Conclusions

Over 98% of PLHIV in care in both CARE sites in Ukraine were receiving ART, and the target of 90% virally suppressed was achieved in persons >6 months on ART. Only one of six HIV/HCV study sites tested over 50% anti-HCV-positive PLHIV for HCV-RNA and treated over 25% of eligible persons. While free HCV-RNA testing and DAA treatment are paramount to achieving HCV elimination targets, they remained a challenge in Ukraine in 2019–2020. The extent of the HIV and HCV care disruption during the war will be further assessed in the CARE cohort and compared with the pre-war findings.     

Human immunodeficiency virus care cascade among sub‐populations in Rakai,Uganda: an observational study

Introduction : To assess progress towards the UNAIDS 90–90–90 initiative targets, we examined the HIV care cascade in the population‐based Rakai Community Cohort Study (RCCS) in rural Uganda and examined differences between sub‐groups. Methods : Self‐reports and clinical records were used to assess the proportion achieving each stage in the cascade. Statistical inference based on a χ² test for categorical variables and modified Poisson regression were used to estimate prevalence risk ratios (PRRs) and 95% confidence intervals (CI) for enrolment into care and initiating antiretroviral therapy (ART). Results : From September 2013 through December 2015, 3,666 HIV‐positive participants were identified in the RCCS. As of December 2015, 98% had received HIV Counseling and Testing (HCT), 74% were enrolled in HIV care, and 63% had initiated ART of whom 92% were virally suppressed after 12 months on ART. Engagement in care was lower among men than women (enrolment in care: adjPRR 0.84, 95% CI 0.77–0.91; ART initiation: adjPRR 0.75, 95% CI 0.69–0.82), persons aged 15–24 compared to those aged 30–39 (enrolment: adjPRR 0.72, 95% CI 0.63–0.82; ART: adjPRR 0.69, 95%CI 0.60–0.80), unmarried persons (enrolment: adjPRR 0.84, 95% CI 0.71–0.99; ART adjPRR 0.80, 95% CI 0.66–0.95), and new in‐migrants (enrolment: adjPRR 0.75, 95% CI 0.67–0.83; ART: adjPRR 0.76, 95% CI 0.67–0.85). This cohort achieved 98–65–92 towards the UNAIDS “90–90–90” targets with an estimated 58% of the entire HIV‐positive RCCS population virally suppressed. Conclusions : This cohort achieved over 90% in both HCT and viral suppression among ART users, but only 65% in initiating ART, likely due to both an ART eligibility criterion of <500 CD4 cells/mL and suboptimal entry into care among men, younger individuals, and in‐migrants. Interventions are needed to promote enrolment in HIV care, particular for hard‐to‐reach sub‐populations.     

The clock is ticking: the rate and timeliness of antiretroviral therapy initiation from the time of treatment eligibility in Kenya

Introduction

Understanding the determinants of timely antiretroviral therapy (ART) initiation is useful for HIV programmes intent on developing models of care that reduce delays in treatment initiation while maintaining a high quality of care. We analysed patient- and facility-level determinants of time to ART initiation among patients who initiated ART in Kenya.

Methods

We collected facility-level information and conducted a retrospective chart review of adults initiating ART between 2007 and 2012 at 51 health facilities in Kenya. We evaluated the association between patient- and facility-level covariates at the time of ART eligibility and time to ART initiation. We also explored the determinants associated with timeliness of ART initiation.

Results

The analysis included 11,942 patients. The median age at the time eligibility was first determined was 37 years (interquartile range [IQR] 31–45). Overall, 75% of patients initiated ART within two months of eligibility. The median CD4 cell count at the time eligibility was first determined rose from 132 (IQR 51–217) in 2007 to 195 (IQR 91–286) in 2011 to 2012 (p<0.001). The cumulative probability of ART initiation among treatment-eligible patients increased over time: 87.1% (95% confidence interval [CI] 85.1–89.0%) in 2007; 96.8% (96.0–97.5%) in 2008; 97.1% (96.3–97.7%) in 2009; 98.5% (98.0 −98.9%) in 2010; and 99.7% (95% CI 99.4 −99.8%) in 2011 to 2012 (p<0.0001). In multivariate analyses, attending a health facility with high ART patient volumes within two months of eligibility was considered the key facility-level determinant of ART initiation (adjusted odds ratio 0.57, 95% CI 0.45–0.72, p<0.001). Patient-level determinants included being eligible for ART in the years subsequent to 2007, advanced World Health Organization clinical stage and low CD4 cell count at the time eligibility was first determined.

Conclusions

Overall, the time between treatment eligibility and ART initiation decreased substantially in Kenya between 2007 and 2012, with uniform gains across different types of health facilities. Our findings highlight the slow increase in CD4 cell counts at the time of ART eligibility over time, indicating that a large number of patients are still beginning ART with advanced HIV disease. Our findings also support the decentralisation of ART services at all health facilities that have the capacity to initiate treatment. Continued evaluation of programme- and country-level data is needed to monitor timeliness of ART initiation as countries continue to expand treatment access.     

Communication between HIV-infected children and their caregivers about HIV medicines: a cross-sectional study in Jinja district,Uganda

Introduction

Knowledge of antiretroviral therapy (ART) among children with HIV depends on open communication with them about their health and medicines. Guidelines assign responsibility for communication to children''s home caregivers. Other research suggests that communication is poor and knowledge about ART is low among children on treatment in low-income countries. This study sought to describe communication about medicine for HIV in quantitative terms from the perspectives of both children and caregivers. Thereafter, it established the factors associated with this communication and with children''s knowledge about their HIV medicines.

Methods

We undertook a cross-sectional survey of a random sample of 394 children with HIV on treatment and their caregivers at nine health facilities in Jinja District, Uganda. We assessed reported frequency and content of communication regarding their medicines as well as knowledge of what the medicines were for. Logistic regression analysis was used to determine the factors associated with communication patterns and children''s knowledge of HIV medicines.

Results

Although 79.6% of the caregivers reported that they explained to the children about the medicines, only half (50.8%) of the children said they knew that they were taking medicines for HIV. Older children aged 15–17 years were less likely to communicate with a caregiver about the HIV medicines in the preceding month (OR 0.5, 95% CI 0.3–0.7, p=0.002). Children aged 11–14 years (OR 6.1, 95% CI 2.8–13.7, p<0.001) and 15–17 years (OR 12.6, 95% CI 4.6–34.3, p<0.001) were more likely to know they were taking medicines for HIV compared to the younger ones. The least common reported topic of discussion between children and caregivers was “what the medicines are for” while “the time to take medicines” was by far the most mentioned by children.

Conclusions

Communication about, and knowledge of, HIV medicines among children with HIV is low. Young age (less than 15 years) was associated with more frequent communication. Caregivers should be supported to communicate diagnosis and treatment to children with HIV. Age-sensitive guidelines about the nature and content of communication should be developed.     

Factors associated with loss to clinic among HIV patients not yet known to be eligible for antiretroviral therapy (ART) in Mozambique

Introduction

Retention in HIV care prior to ART initiation is generally felt to be suboptimal, but has not been well-characterized.

Methods

We examined data on 37,352 adult pre-ART patients (ART ineligible or unknown eligibility) who enrolled in care during 2005–2008 with >1 clinical visit at 23 clinics in Mozambique. We defined loss to clinic (LTC) as >12 months since the last visit among those not known to have died/transferred. Cox proportional-hazards models were used to examine factors associated with LTC, accounting for clustering within sites.

Results

Of 37,352 pre-ART patients, 61% had a CD4 count within three months of enrolment (median CD4: 452, IQR: 345–611). 17,598 (47.1%) were ART ineligible and 19,754 (52.9%) were of unknown eligibility status at enrolment because of missing information on CD4 count and/or WHO stage. Kaplan-Meier estimates for LTC at 12 months were 41% (95% CI: 40.2–41.8) and 48% (95% CI: 47.2–48.8), respectively. Factors associated with LTC among ART ineligible patients included male sex (AHR_{men_vs_non-pregnant women}: 1.5; 95% CI: 1.4–1.6) and being pregnant at enrolment (AHR_{pregnant_vs_non-pregnant women}: 1.3; 95% CI: 1.1–1.5). Older age, more education, higher weight and more advanced WHO stage at enrolment were independently associated with lower risks of LTC. Similar findings were observed among patients whose ART eligibility status was unknown at enrolment.

Conclusions

Substantial LTC occurred prior to ART initiation among patients not yet known to be eligible for ART, including nearly half of patients without documented ART eligibility assessment. Interventions are needed to target pre-ART patients who may be at higher risk for LTC, including pregnant women and patients with less advanced HIV disease.     

A modelling framework for translating discrete choice experiment results into cost-effectiveness estimates: an application to designing tailored and scalable HIV and contraceptive services for adolescents in Gauteng,South Africa

Introduction

South African youth and adolescents face a high burden of (Sexually Transmitted Infections) STIs, HIV and unintended pregnancies, but uptake of services remains low. To address this, tailored and scalable interventions are urgently needed. We developed a framework to fill the gap and translate the impact of facility-level attributes into a cost-effectiveness analysis for increasing HIV/contraceptive service uptake in adolescents using a discrete choice experiment (DCE).

Methods

We used a DCE (n = 805) conducted in Gauteng, South Africa, which found that staff attitude, confidentiality, Wi-Fi, subsidized food, afternoon hours and youth-only services were preferred attributes of health services. Based on this, we simulated the uptake of services adapted for these preferences. We divided preferences into modifiable attributes that could readily be adapted (e.g. Wi-Fi), and challenging to modify (more nuanced attributes that are more challenging to cost and evaluate): staff attitude and estimated the incremental change in the uptake of services using adapted services. Costs for modifiable preferences were estimated using data from two clinics in South Africa (2019 US$). We determined the incremental cost-effectiveness ratio (ICER) for additional adolescents using services of 15 intervention combinations, and report the results of interventions on the cost-effectiveness frontier.

Results

Greatest projected impact on uptake was from friendly and confidential services, both of which were considered challenging to modify (18.5% 95% CI: 13.0%−24.0%; 8.4% 95% CI: 3.0%−14.0%, respectively). Modifiable factors on their own resulted in only small increases in expected uptake. (Food: 2.3% 95% CI: 4.0%−9.00%; Wi-Fi: 3.0% 95% CI: −4.0% to 10.0%; Youth-only services: 0.3% 95% CI: −6.0% to 7.0%; Afternoon services: 0.8% 95% CI: −6.0% to 7.0%). The order of interventions on the cost-effectiveness frontier are Wi-Fi and youth-only services (ICER US$7.01−US$9.78 per additional adolescent utilizing HIV and contraceptive services), Wi-Fi, youth-only services and food (ICER US$9.32−US$10.45), followed by Wi-Fi, youth-only services and extended afternoon hours (ICER US$14.46–US$43.63).

Conclusions

Combining DCE results and costing analyses within a modelling framework provides an innovative way to inform decisions on effective resource utilization. Modifiable preferences, such as Wi-Fi provision, youth-only services and subsidized food, have the potential to cost-effectively increase the proportion of adolescents accessing HIV and contraceptive services.     

Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau – a retrospective cohort study

Introduction

With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau.

Methods

In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up.

Results

We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8).

Conclusions

We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.     

Adolescent pregnancy at antiretroviral therapy (ART) initiation: a critical barrier to retention on ART

Introduction

Adolescence and pregnancy are potential risk factors for loss to follow‐up (LTFU) while on antiretroviral therapy (ART). We compared adolescent and adult LTFU after ART initiation to quantify the impact of age, pregnancy, and site‐level factors on LTFU.

Methods

We used routine clinical data for patients initiating ART as young adolescents (YA; 10 to 14 years), older adolescents (OA; 15 to 19 years) and adults (≥20 years) from 2000 to 2014 at 52 health facilities affiliated with the International epidemiology Databases to Evaluate AIDS (IeDEA) East Africa collaboration. We estimated cumulative incidence (95% confidence interval, CI) of LTFU (no clinic visit for ≥6 months after ART initiation) and identified patient and site‐level correlates of LTFU, using multivariable Cox proportional hazards models for all patients as well as individual age groups.

Results

A total of 138,387 patients initiated ART, including 2496 YA, 2955 OA and 132,936 adults. Of these, 55%, 78% and 66%, respectively, were female and 0.7% of YA, 22.3% of OA and 8.3% of adults were pregnant at ART initiation. Cumulative incidence of LTFU at five years was 26.6% (24.6 to 28.6) among YA, 44.1% (41.8 to 46.3) among OA and 29.3% (29.1 to 29.6) among adults. Overall, compared to adults, the adjusted hazard ratio, aHR, (95% CI) of LTFU for OA was 1.54 (1.41 to 1.68) and 0.77 (0.69 to 0.86) for YA. Compared to males, pregnant females had higher hazard of LTFU, aHR 1.20 (1.14 to 1.27), and nonpregnant women had lower hazard aHR 0.90 (0.88 to 0.93). LTFU hazard among the OA was primarily driven by both pregnant and nonpregnant females, aHR 2.42 (1.98 to 2.95) and 1.51 (1.27 to 1.80), respectively, compared to men. The LTFU hazard ratio varied by IeDEA program. Site‐level factors associated with overall lower LTFU hazard included receiving care in tertiary versus primary‐care clinics aHR 0.61 (0.56 to 0.67), integrated adult and adolescent services and food ration provision aHR 0.93 (0.89 to 0.97) versus nonintegrated clinics with food ration provision, having patient support groups aHR 0.77 (0.66 to 0.90) and group adherence counselling aHR 0.61 (0.57 to 0.67).

Conclusions

Older adolescents experienced higher risk of LTFU compared to YA and adults. Interventions to prevent LTFU among older adolescents are critically needed, particularly for female and/or pregnant adolescents.