Outcomes of patients lost to follow-up after antiretroviral therapy initiation in rural north-eastern South Africa.

OBJECTIVE: The vital status of patients lost to follow-up often remains unknown in antiretroviral therapy (ART) programmes in sub-Saharan Africa because medical records are no longer updated once the patient disengages from care. Thus, we aimed to assess the outcomes of patients lost to follow-up after ART initiation in north-eastern South Africa. METHODS: Using data from a rural area in north-eastern South Africa, we estimated the cumulative incidence of patient outcomes (i) after treatment initiation using clinical records, and (ii) after loss to follow-up (LTFU) using data from clients that have been individually linked to Agincourt Health and Demographic Surveillance System (AHDSS) database. Aside from LTFU, we considered mortality, re-engagement and migration out of the study site. Cox proportional hazards regression was used to identify covariates of these patient outcomes. RESULTS: Between April 2014 and July 2017, 3700 patients initiated ART and contributed a total of 6818 person-years of follow-up time. Three years after ART initiation, clinical record-based estimates of LTFU, mortality and documented transfers were 41.0% (95% CI: 38.5-43.4%), 1.9% (95% CI 1.0-3.2%) and 0.1% (95% CI 0.0-0.9%), respectively. Among those who were LTFU, the cumulative incidence of re-engagement, out-migration and mortality at 3 years were 38.1% (95% CI 33.1-43.0%), 49.4% (95% CI 43.1-55.3%) and 4.7% (95% CI 3.5-6.2%), respectively. Pregnant or breastfeeding women, foreigners and those who initiated ART most recently were at an increased risk of LTFU. CONCLUSION: LTFU among patients starting ART in north-eastern South Africa is relatively high and has increased in recent years as more asymptomatic patients have initiated treatment. Even though this tendency is of concern in light of the prevention of onwards transmission, we also found that re-engagement in care is common and mortality among persons LTFU relatively low.

OBJECTIF: Le statut vital des patients perdus au suivi reste souvent inconnu dans les programmes de traitement antirétroviral (ART) en Afrique subsaharienne parce que les dossiers médicaux ne sont plus mis à jour une fois que le patient se désengage des soins. Notre objectif était d'évaluer les résultats des patients dans le nord-est de l'Afrique du Sud. MÉTHODES: A l'aide de données provenant d'une zone rurale du nord-est de l'Afrique du Sud, nous avons estimé l'incidence cumulée des résultats pour les patients (i) après le début du traitement à l'aide des dossiers cliniques et (ii) après la perte au suivi (PS) à l'aide des données des patients qui ont été reliées individuellement à la base de données du système de surveillance démographique et de santé (AHDSS) d'Agincourt. Outre les PS, nous avons pris en compte la mortalité, le réengagement et la migration hors du site de l'étude. La régression des risques proportionnels de Cox a été utilisée pour identifier les covariables de ces résultats pour le patient. RÉSULTATS: Entre avril 2014 et juillet 2017, 3.700 patients ont commencé l'ART constituant un suivi total de 6.818 années-personnes. Trois ans après le début de l'ART, les estimations des PS, de la mortalité et des transferts documentés selon les registres cliniques étaient de 41,0% (IC95%: 38,5% à 43,4%), 1,9% (IC95%: 1,0% à 3,2%) et 0,1% (IC95%: 0,0% -0,9%), respectivement. Parmi ceux qui étaient PS, l'incidence cumulative de réengagement, d'émigration et de mortalité à trois ans était de 38,1% (IC95%: 33,1% à 43,0%), 49,4% (IC95%: 43,1% à 55,3%) et 4,7% (IC95%: 3,5% -6,2%), respectivement. Les femmes enceintes ou allaitantes, les étrangers et les personnes qui ont commencé l'ART le plus récemment couraient un risque accru de PS. CONCLUSION: La PS chez les patients commençant une ART dans le nord-est de l'Afrique du Sud est relativement élevée et a augmenté ces dernières années à mesure que davantage de patients asymptomatiques ont commencé le traitement. Même si cette tendance est préoccupante à la lumière de la prévention de la transmission, nous avons également constaté que le réengagement dans les soins était courant et que la mortalité parmi les PS était relativement faible.

From policy to practice: exploring the implementation of antiretroviral therapy access and retention policies between 2013 and 2016 in six sub-Saharan African countries.

BACKGROUND: Understanding the implementation of 2013 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection at the facility level provides important lessons for the roll-out of future HIV policies. METHODS: A national policy review was conducted in six sub-Saharan African countries to map the inclusion of the 2013 WHO HIV treatment recommendations. Twenty indicators of policy adoption were selected to measure ART access (n = 12) and retention (n = 8). Two sequential cross-sectional surveys were conducted in facilities between 2013/2015 (round 1) and 2015/2016 (round 2) from ten health and demographic surveillance sites in Kenya, Malawi, South Africa, Tanzania, Uganda and Zimbabwe. Using standardised questionnaires, facility managers were interviewed. Descriptive analyses were used to assess the change in the proportion of facilities that implemented these policy indicators between rounds. RESULTS: Although, expansion of ART access was explicitly stated in all countries' policies, most lacked policies that enhanced retention. Overall, 145 facilities were included in both rounds. The proportion of facilities that initiated ART at CD4 counts of 500 or less cells/µL increased between round 1 and 2 from 12 to 68%, and facilities initiating patients on 2013 WHO recommended ART regimen increased from 42 to 87%. There were no changes in the proportion of facilities reporting stock-outs of first-line ART in the past year (18 to 11%) nor in the provision of three-month supply of ART (43 to 38%). None of the facilities provided community-based ART delivery. CONCLUSION: The increase in ART initiation CD4 threshold in most countries, and substantial improvements made in the provision of WHO recommended first-line ART regimens demonstrates that rapid adoption of WHO recommendations is possible. However, improved logistics and resources and/or changes in policy are required to further minimise ART stock-outs and allow lay cadres to dispense ART in the community. Increased efforts are needed to offer longer durations between clinic visits, a strategy purported to improve retention. These changes will be important as countries move to implement the revised 2015 WHO guidelines to initiate all HIV positive people onto ART regardless of their immune status.

Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials.

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7 days had the highest PPV, while pill-count data consistent with missing ≤1 day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p = 0.014) and weeks of time in the study (OR 1.02; p < 0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed.

Comparison of programmatic data from antenatal clinics with population-based HIV prevalence estimates in the era of universal test and treat in western Kenya.

OBJECTIVE: To compare HIV prevalence estimates from routine programme data in antenatal care (ANC) clinics in western Kenya with HIV prevalence estimates in a general population sample in the era of universal test and treat (UTT). METHODS: The study was conducted in the area covered by the Siaya Health Demographic Surveillance System (Siaya HDSS) in western Kenya and used data from ANC clinics and the general population. ANC data (n = 1,724) were collected in 2018 from 13 clinics located within the HDSS. The general population was a random sample of women of reproductive age (15-49) who reside in the Siaya HDSS and participated in an HIV sero-prevalence survey in 2018 (n = 2,019). Total and age-specific HIV prevalence estimates were produced from both datasets and demographic decomposition methods were used to quantify the contribution of the differences in age distributions and age-specific HIV prevalence to the total HIV prevalence estimates. RESULTS: Total HIV prevalence was 18.0% (95% CI 16.3-19.9%) in the ANC population compared with 18.4% (95% CI 16.8-20.2%) in the general population sample. At most ages, HIV prevalence was higher in the ANC population than in the general population. The age distribution of the ANC population was younger than that of the general population, and because HIV prevalence increases with age, this reduced the total HIV prevalence among ANC attendees relative to prevalence standardised to the general population age distribution. CONCLUSION: In the era of UTT, total HIV prevalence among ANC attendees and the general population were comparable, but age-specific HIV prevalence was higher in the ANC population in most age groups. The expansion of treatment may have led to changes in both the fertility of women living with HIV and their use of ANC services, and our results lend support to the assertion that the relationship between ANC and general population HIV prevalence estimates are highly dynamic.

Prevalence of cryptosporidiosis in dairy cattle, cattle-keeping families, their non-cattle-keeping neighbours and HIV-positive individuals in Dagoretti Division, Nairobi, Kenya.

This paper reports a study estimating the prevalence of cryptosporidiosis, an emerging zoonosis, in people and cattle in Dagoretti, Nairobi. A repeated cross-sectional survey was carried out among randomly selected cattle keepers in Dagoretti, their dairy cattle and their non-cattle-keeping neighbours in the dry and wet seasons of 2006. A survey was also carried out among a group of people living with human immunodeficiency virus (HIV). Faecal samples were examined for Cryptosporidium oocysts using the modified Ziehl-Neelsen method; 16 % of the samples were also examined using immunofluorescence antibody (IFA) technique. Quality control consisted of blind reviews of slides, examining split samples and confirming slide results with IFA. We found that members of dairy households had a dry season cryptosporidiosis prevalence of 4 % and wet season prevalence of 0.3 %, and non-dairy households, a prevalence of 5 and 0 %, respectively. The cattle dry season prevalence was 15 %, and the wet season prevalence, 11 %. The prevalence in people living with HIV was 5 %. The laboratory quality control system showed some inconsistency within and between different tests, indicating challenges in obtaining consistent results under difficult field and working conditions. In conclusion, this is the first reported study to simultaneously survey livestock, livestock keepers and their neighbours for cryptosporidiosis. We failed to find evidence that zoonotic cryptosporidiosis is important overall in this community. This study also draws attention to the importance of quality control and its reporting in surveys in developing countries.

Development and delivery of evidence-based messages to reduce the risk of zoonoses in Nairobi, Kenya.

This paper describes a trans-disciplinary process of co-generating and disseminating evidence-based messages for reducing the risk from cryptosporidiosis and other zoonoses in an urban community in Nairobi. Research findings about disease prevalence, risk factors and observed risky and risk-mitigating practices were analysed by a team comprising researchers, community members and local policy- and decision-makers. Using participatory planning, multiple strategies were developed for disseminating key information. We identified five vulnerable groups at higher risk of exposure to cryptosporidiosis and other cattle zoonoses with similar transmission pathways (women, children, elderly people, immunosuppressed people and male farm workers). For each group, targeted messages were developed. Good practices already in use, as were also practices as practices to improve environmental conditions. These messages were disseminated through printed material, in a workshop, through community campaigners and also an edutainment soap opera episode broadcast on Kenyan television. In conclusion, a participatory and trans-disciplinary process can help transform the findings of research into messages that are targeted, attractive and understandable.

Social and gender determinants of risk of cryptosporidiosis, an emerging zoonosis, in Dagoretti, Nairobi, Kenya.

The aim of the study was to investigate the social and gender determinants of the risk of exposure to Cryptosporidium from urban dairying in Dagoretti, Nairobi. Focus group discussions were held in six locations to obtain qualitative information on risk of exposure. A repeated cross-sectional descriptive study included participatory assessment and household questionnaires (300 randomly selected urban dairy farming households and 100 non-dairying neighbours). One-hundred dairy households randomly selected from the 300 dairy households participated in an additional economic survey along with 40 neighbouring non-dairy households. We found that exposure to Cryptosporidium was influenced by gender, age and role in the household. Farm workers and people aged 50 to 65 years had most contact with cattle, and women had greater contact with raw milk. However, children had relatively higher consumption of raw milk than other age groups. Adult women had more daily contact with cattle faeces than adult men, and older women had more contact than older men. Employees had greater contact with cattle than other groups and cattle faeces, and most (77 %) were male. Women took more care of sick people and were more at risk from exposure by this route. Poverty did not affect the level of exposure to cattle but did decrease consumption of milk. There was no significant difference between men and women as regards levels of knowledge on symptoms of cryptosporidiosis infections or other zoonotic diseases associated with dairy farming. Awareness of cryptosporidiosis and its transmission increased significantly with rising levels of education. Members of non-dairy households and children under the age of 12 years had significantly higher odds of reporting diarrhoea: gender, season and contact with cattle or cattle dung were not significantly linked with diarrhoea. In conclusion, social and gender factors are important determinants of exposure to zoonotic disease in Nairobi.

Evaluating pregnancy reporting in Siaya Health and Demographic Surveillance System through record linkage with ANC clinics.

Introduction: Health and Demographic Surveillance Systems (HDSS) are important sources of population health data in sub-Saharan Africa, but the recording of pregnancies, pregnancy outcomes, and early mortality is often incomplete. Objective: This study assessed HDSS pregnancy reporting completeness and identified predictors of unreported pregnancies that likely ended in adverse outcomes. Methods: The analysis utilized individually-linked HDSS and antenatal care (ANC) data from Siaya, Kenya for pregnancies in 2018-2020. We cross-checked ANC records with HDSS pregnancy registrations and outcomes. Pregnancies observed in the ANC that were missing reports in the HDSS despite a data collection round following the expected delivery date were identified as likely adverse outcomes, and we investigated the characteristics of such individuals. Clinical data were used to investigate the timing of HDSS pregnancy registration relative to care seeking and gestational age, and examine misclassification of miscarriages and stillbirths. Results: From an analytical sample of 2,475 pregnancies observed in the ANC registers, 46% had pregnancy registrations in the HDSS, and 89% had retrospectively reported pregnancy outcomes. 1% of registered pregnancies were missing outcomes, compared to 10% of those lacking registration. Registered pregnancies had higher rates of stillbirth and perinatal mortality than those lacking registration. In 77% of cases, women accessed ANC prior to registering the pregnancy in the HDSS. Half of reported miscarriages were misclassified stillbirths. We identified 141 unreported pregnancies that likely ended in adverse outcomes. Such cases were more common among those who visited ANC clinics during the first trimester, made fewer overall visits, were HIV-positive, and outside of formal union. Conclusions: Record linkage with ANC clinics revealed pregnancy underreporting in HDSS, resulting in biased measurement of perinatal mortality. Integrating records of ANC usage into routine data collection can augment HDSS pregnancy surveillance and improve monitoring of adverse pregnancy outcomes and early mortality.

A systematic review of interventions to improve prevention of mother-to-child HIV transmission service delivery and promote retention.

INTRODUCTION: The success of prevention of mother-to-child transmission of HIV (PMTCT) is dependent upon high retention of mother-infant pairs within these programmes. This is a systematic review to evaluate the effectiveness of interventions that aim to improve PMTCT service delivery and promote retention throughout the PMTCT steps. METHODS: Selected databases were searched for studies published in English (up to September 2015). Outcomes of interest included antiretroviral (ARV) drugs or antiretroviral therapy (ART) initiation among HIV-positive pregnant and/or breastfeeding women and their infants, retention into PMTCT programs, the uptake of early infant diagnosis (EID) of HIV and infant HIV status. Risk ratios and random-effect meta-analysis were used in the analysis. RESULTS: Interventions assessed in the 34 identified studies included male partner involvement in PMTCT, peer mentoring, the use of community health workers (CHWs), mobile phone-based reminders, conditional cash transfer, training of midwives, integration of PMTCT services and enhanced referral. Five studies (two randomized) that evaluated mobile phone-based interventions showed a statistically significant increase (pooled RR 1.18; 95% CI 1.05 to 1.32, I(2)=83%) in uptake of EID of HIV at around six weeks postpartum. Male partner involvement in PMTCT was associated with reductions in infant HIV transmission (pooled RR 0.61; 95% CI 0.39 to 0.94, I(2)=0%) in four studies (one randomized). Four studies (three randomized) that were grounded on psychological interventions reported non-significant results (pooled RR 1.01; 95% CI 0.93 to 1.09, I(2)=69%) in increasing ARV/ART uptake among HIV-positive pregnant and/or breastfeeding women and infant HIV testing (pooled RR 1.00; 95% CI 0.94 to 1.07, I(2)=45%). The effect of the other interventions on the effectiveness of improving PMTCT uptake was unclear. Heterogeneity of interventions limits these findings. CONCLUSIONS: Our findings indicate that mobile phone-based reminders may increase the uptake of EID of HIV. Studies on male partner involvement in PMTCT reported reductions in infant HIV transmission. Stronger evidence is needed and future studies should determine the long-term effects of these interventions in improving retention throughout the PMTCT steps.

Neurological syndrome in an HIV-prevention trial participant randomized to daily tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) in Bondo, Kenya.

Side effects of antiretroviral drug use by HIV-positive patients have been extensively studied; however, there are limited data on the side effects of antiretroviral drugs used as an HIV prophylaxis among healthy, HIV-negative individuals. Here we report on an unusual neuropathy in a 24-year-old participant in the FEM-PrEP trial. This was a Phase III randomized, double blind, placebo-controlled trial to test the safety and effectiveness of tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) (TDF-FTC) to prevent HIV. At the eighth week of taking TDF-FTC with moderate adherence, the participant complained of mild paresthesiae, numbness, and a tingling sensation in her upper limbs that was associated with pain and cold. After an additional 4 days, she developed a disabling weakness of her upper limbs and tremors in her hands. The study product was discontinued, and within 2 weeks she was free of all symptoms. One month after restarting the drug, she complained of posture-dependent numbness of her upper limbs. Results of clinical and neurological exams, laboratory tests, and magnetic resonance imaging are described here.