Attrition from Care Among Men Initiating ART in Male-Only Clinics Compared with Men in General Primary Healthcare Clinics in Khayelitsha, South Africa: A Matched Propensity Score Analysis.

Men have higher rates of attrition from antiretroviral therapy (ART) programs than women. In Khayelitsha, a high HIV prevalence area in South Africa, two public sector primary healthcare clinics offer services, including HIV testing and treatment, exclusively to men. We compared attrition from ART care among men initiating ART at these clinics with male attrition in six general primary healthcare clinics in Khayelitsha. We described baseline characteristics of patients initiating ART at the male and general clinics from 1 January 2014 to 31 March 2018. We used exposure propensity scores (generated based on baseline health and age) to match male clinic patients 1:1 to males at other clinics. The association between attrition (death or loss to follow-up, defined as no visits for nine months) and clinic type was estimated using Cox proportional hazards regression. Follow-up time began at ART initiation and ended at attrition, clinic transfer, or dataset closure. Before matching, patients from male clinics (n = 784) were younger than males from general clinics (n = 2726), median age: 31.2 vs 35.5 years. Those initiating at male clinics had higher median CD4 counts at ART initiation [Male Clinic 1: 329 (IQR 210-431), Male Clinic 2: 364 (IQR 260-536), general clinics 258 (IQR 145-398), cells/mm3]. In the matched analysis (1451 person-years, 1568 patients) patients initiating ART at male clinics had lower attrition (HR 0.71; 95% CI 0.60-0.85). In separate analyses for each of the two male clinics, only the more established male clinic showed a protective effect. Male-only clinics reached younger, healthier men, and had lower ART attrition than general services. These findings support clinic-specific adaptations to create more male-friendly environments.

Delivering PrEP to Young Women in a Low-Income Setting in South Africa: Lessons for Providing Both Convenience and Support.

Daily oral pre-exposure prophylaxis (PrEP) is a key tool in addressing high HIV incidence among young women, and breaking the cycle of transmission. From 2017 to 2020, Médecins Sans Frontières (MSF) offered PrEP, in conjunction with contraception and risk-reduction counselling, to women aged 18-25, in a government-run clinic in Khayelitsha, a low income high HIV prevalence area in South Africa. Drawing on clinical, quantitative, and qualitative interview data, we describe participants' experiences and engagement with the PrEP program, participant adherence (measured by TFV-DP levels in dried blood spots) over time, and the indirect benefits of the PrEP program. Of 224 screened and eligible participants, 164 (73.2%) initiated PrEP, with no large differences between those who initiated and those who did not. Overall, 47 (29%) completed 18 months follow-up, with 15 (9.1%) attending all visits. 76 (46.9%) participants were lost to follow-up, 15 (9.1%) exited when leaving the area, and 28.7% of exits happened in the first month of the study. We identified two different trajectories of PrEP adherence: 67% of participants had, on average, consistently low TFV-DP levels, with the remaining 33% having sustained high adherence. Few baseline characteristics predicted good adherence. The main reported barrier to taking PrEP was forgetting to take or travel with the pills. Encouragement from others declined as a reported facilitator from month 6 to 18 (family: 93.1% vs 77.6%, p = 0.016, friends: 77.6% vs 41.4%, p ≤ 0.001, partners: 62.1% vs 46.6%, p = 0.096, other PrEP users: 89.7% vs 74.1%, p = 0.020). Disclosure to friends and family in some cases opened dialogue around sex, and helped to educate others about PrEP. Self-reported sex with more than one partner, and sex without a condom, decreased significantly after enrolment (p < 0.001, p = 0.063). In the individual interviews, participants credited their PrEP experience with changing their behaviour. Recognising the challenges with, but overall benefits from a package of care that includes the option of PrEP, lessons drawn from this study can help maximise persistence on PrEP within resource constraints. PrEP providers need to address participants' need for both convenience and social support.

Knowledge transmission, peer support, behaviour change and satisfaction in post Natal clubs in Khayelitsha, South Africa: a qualitative study.

BACKGROUND: The Post Natal Club (PNC) model assures comprehensive care, including HIV and Maternal and Child Health care, for postpartum women living with HIV and their infants during an 18-month postnatal period. The PNC model was launched in 2016 in Town Two Clinic, a primary health care facility in Khayelitsha, South Africa. This qualitative research study aims to understand how participation in PNCs affected knowledge transmission, peer support, behaviour change and satisfaction with the care provided. METHODS: We conducted ten in-depth interviews; three focus group discussions and participant observation with PNC members, health-care workers and key informants selected through purposive sampling. Seventeen PNC members between 21 and 38 years old, three key informants and seven staff working in PNC participated in the research. All participants were female, except for one of the three key informants who was male. Data was collected until saturation. The data analysis was performed in an inductive way and involved an iterative process, using Nvivo11 software. RESULTS: PNC members acquired knowledge on HIV, ART, adherence, infant feeding, healthy eating habits, follow up tests and treatment for exposed infants. Participants believed that PNC created strong relationships among members and offered an environment conducive to sharing experience and advice. Most interviewees stated that participating in PNC facilitated disclosure of their HIV status, enhanced support network and provided role models. PNC members said that they adapted their behaviour based on advice received in PNCs related to infant feeding, ART adherence, monitoring of symptoms and stimulation of early childhood development. The main benefits were believed to be comprehensive care for mother-infant pairs, time-saving and the peer dynamic. The main challenge from the perspective of key informants was the sustainability of dedicating human resources to PNC. CONCLUSION: The PNC model was believed to improve knowledge acquisition, behaviour change and peer support. Participants, staff and the majority of key informants expressed a high level of satisfaction with the PNC model. Sustainability and finding adequate human resources for PNCs remained challenging. Strategies to improve sustainability may include handing over some PNC tasks to members to increase their sense of ownership.

Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa.

Experience with delamanid (Dlm) is limited, particularly among HIV-positive individuals. We describe early efficacy and safety data from a programmatic setting in South Africa.This was a retrospective cohort study of patients receiving Dlm-containing treatment regimens between November 2015 and August 2017. We report 12-month interim outcomes, sputum culture conversion (SCC) by months 2 and 6, serious adverse events (SAEs) and QT intervals corrected using the Frederica formula (QTcF).Overall, 103 patients were initiated on Dlm; 79 (77%) were HIV positive. The main indication for Dlm was intolerance to second-line anti-tuberculosis (TB) drugs (n=58, 56%). There were 12 months of follow-up for 46 patients; 28 (61%) had a favourable outcome (cure, treatment completion or culture negativity). Positive cultures were found for 57 patients at Dlm initiation; 16 out of 31 (52%) had SCC within 2 months and 25 out of 31 (81%) within 6 months. There were 67 SAEs reported in 29 patients (28%). There were four instances of QTcF prolongation >500 ms in two patients (2%), leading to permanent discontinuation in one case; however, no cardiac arrhythmias occurred.This large cohort of difficult-to-treat patients receiving Dlm for rifampicin-resistant TB treatment in a programmatic setting with high HIV prevalence had favourable early treatment response and tolerated treatment well. Dlm should remain available, particularly for those who cannot be treated with conventional regimens or with limited treatment options.

Independent predictors of tuberculosis mortality in a high HIV prevalence setting: a retrospective cohort study.

BACKGROUND: Identifying those at increased risk of death during TB treatment is a priority in resource-constrained settings. We performed this study to determine predictors of mortality during TB treatment. METHODS: We performed a retrospective analysis of a TB surveillance population in a high HIV prevalence area that was recorded in ETR.net (Electronic Tuberculosis Register). Adult TB cases initiated TB treatment from 2007 through 2009 in Khayelitsha, South Africa. Cox proportional hazards models were used to identify risk factors for death (after multiple imputations for missing data). Model selection was performed using Akaike's Information Criterion to obtain the most relevant predictors of death. RESULTS: Of 16,209 adult TB cases, 851 (5.3 %) died during TB treatment. In all TB cases, advancing age, co-infection with HIV, a prior history of TB and the presence of both pulmonary and extra-pulmonary TB were independently associated with an increasing hazard of death. In HIV-infected TB cases, advancing age and female gender were independently associated with an increasing hazard of death. Increasing CD4 counts and antiretroviral treatment during TB treatment were protective against death. In HIV-uninfected TB cases, advancing age was independently associated with death, whereas smear-positive disease was protective. CONCLUSION: We identified several independent predictors of death during TB treatment in resource-constrained settings. Our findings inform resource-constrained settings about certain subgroups of TB patients that should be targeted to improve mortality during TB treatment.

Reciprocal seasonal variation in vitamin D status and tuberculosis notifications in Cape Town, South Africa.

Vitamin D deficiency is associated with susceptibility to tuberculosis (TB) in HIV-uninfected people in Europe, but it is not known whether such an association exists among HIV-infected people in subtropical Africa. We conducted a cross-sectional study to determine whether vitamin D deficiency was associated with susceptibility to active TB in HIV-uninfected (n = 196) and HIV-infected (n = 174) black Africans in Cape Town, South Africa. We also investigated whether there was evidence of seasonal variation in vitamin D status and TB notifications in this setting over an 8-y period. Vitamin D deficiency (serum 25-hydroxyvitamin D [25(OH)D] <50 nmol/L) was present in 232 (62.7%) of 370 participants and was associated with active TB in both HIV-uninfected (odds ratio = 5.2, 95% confidence interval: 2.8-9.7; P < 0.001) and HIV-infected (odds ratio = 5.6, 95% confidence interval: 2.7-11.6; P < 0.001) people. Vitamin D status varied according to season: The mean serum 25(OH)D concentration was highest in January through March and lowest in July through September (56.8 vs. 30.7 nmol/L, respectively; P < 0.001). Reciprocal seasonal variation in TB notifications was observed: The mean number of TB notifications per quarter for Cape Town in 2003 to 2010 was lowest in April through June and highest in October through December (4,222 vs. 5,080; P < 0.001). Vitamin D deficiency is highly prevalent among black Africans in Cape Town and is associated with susceptibility to active TB both in the presence and absence of HIV infection. Reciprocal seasonal variation in serum 25(OH)D concentration and TB notifications suggests that seasonal variations in vitamin D status and TB incidence in this setting are causally related.

Postnatal clubs: Implementation of a differentiated and integrated model of care for mothers living with HIV and their HIV-exposed uninfected babies in Cape Town, South Africa.

BACKGROUND: Despite the overall reduction in the HIV mother-to-child transmission (MTCT) rate in South Africa, poor adherence and retention in care during breastfeeding contribute to this period being a major driver of MTCT in South Africa. To improve this retention, postnatal clubs were created as an integrated, differentiated model of care providing psychosocial support and comprehensive care for the mother-infant pairs (MIP), including HIV and under-5-child services. We describe the implementation of these facility-based clubs and examine its health outcomes in a peri-urban primary health care setting in Cape Town, South Africa. METHODS: In this prospective cohort study, conducted between June 2016 and December 2019, MIPs were recruited into postnatal clubs between 6 weeks and 6 months of age and followed-up until 18 months of age. Outcomes including maternal Viral Load (VL), and children's HIV testing were compared to a historical control group. Children's immunizations and maternal sexual and reproductive health outcomes are also described. RESULTS: During the implementation of the postnatal club study period, 484 MIP were recruited with 84% overall attendance, 95% overall viral load suppression, and 98% overall uptake of HIV infant testing. Compared to historical controls, the club infant rapid test uptake was 1.6 times higher (95% CI: 1.4-1.9) at 9 months and 2.0 times higher at 18 months (95% CI: 1.6-2.6). Through 12 months and between 12-18 months, maternal VL monitoring was higher in the club group compared to the historical control by 1.5 times (95% CI: 1.3-1.6) and 2.6 times (95% CI: 2.1-3.2), respectively, with similar maternal VL suppression. Of 105 infants attending the 12 months visit, 99% were fully vaccinated by one year. CONCLUSION: MIP in the postnatal clubs showed better PMTCT outcomes than historical controls with high levels of retention in care. Other outcomes such as immunisation results suggest that integration of services, such as in the postnatal club, is feasible and beneficial for MIPs.

Attrition from HIV care among youth initiating ART in youth-only clinics compared with general primary healthcare clinics in Khayelitsha, South Africa: a matched propensity score analysis.

INTRODUCTION: Youth living with HIV (YLWH) are less likely to initiate antiretroviral therapy (ART) and remain in care than older adults. It is important to identify effective strategies to address the needs of this growing population and prevent attrition from HIV care. Since 2008, two clinics have offered youth-targeted services exclusively to youth aged 12-25 in Khayelitsha, a high HIV-prevalence, low-income area in South Africa. We compared ART attrition among youth in these two clinics to youth in regular clinics in the same area. METHODS: We conducted a propensity score matched cohort study of individuals aged 12-25 years initiating ART at eight primary care clinics in Khayelitsha between 1 January 2008 and 1 April 2018. We compared attrition, defined as death or loss to follow-up, between those attending two youth clinics and those attending general primary healthcare clinics, using Cox proportional hazards regression. Follow-up time began at ART initiation and ended at attrition, clinic transfer or dataset closure. We conducted sub-analyses of patients attending adherence clubs. RESULTS: The distribution of age, sex and CD4 count at ART initiation was similar across Youth Clinic A (N = 1383), Youth Clinic B (N = 1299) and general clinics (N = 3056). Youth at youth clinics were more likely than those at general clinics to have initiated ART before August 2011 (Youth Clinic A: 16%, Youth Clinic B: 23% and general clinics: 11%). Youth clinics were protective against attrition: HR 0.81 (95% CI: 0.71-0.92) for Youth Clinic A and 0.85 (0.74-0.98) for Youth Clinic B, compared to general clinics. Youth Clinic A club patients had lower attrition after joining an adherence club than general clinic patients in adherence clubs (crude HR: 0.56, 95% CI: 0.32-0.96; adjusted HR: 0.48, 95% CI: 0.28-0.85), while Youth Clinic B showed no effect (crude HR: 0.83, 95% CI: 0.48-1.45; adjusted HR: 1.07, 95% CI: 0.60-1.90). CONCLUSIONS: YLWH were more likely to be retained in ART care in two different youth-targeted clinics compared to general clinics in the same area. Our findings suggest that multiple approaches to making clinics more youth-friendly can contribute to improving retention in this important group.

Clinical deterioration during antituberculosis treatment in Africa: incidence, causes and risk factors.

BACKGROUND: HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration. METHODS: Prospective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment. RESULTS: Seventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/microL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/microL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/microL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/microL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/microL. CONCLUSIONS: In multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/microL will likely reduce the high burden of clinical deterioration.

The failure of routine rapid HIV testing: a case study of improving low sensitivity in the field.

BACKGROUND: The rapid HIV antibody test is the diagnostic tool of choice in low and middle-income countries. Previous evidence suggests that rapid HIV diagnostic tests may underperform in the field, failing to detect a substantial number of infections. A research study inadvertently discovered that a clinic rapid HIV testing process was failing to detect cases of established (high antibody titer) infection, exhibiting an estimated 68.7% sensitivity (95% CI [41.3%-89.0%]) over the course of the first three weeks of observation. The setting is a public service clinic that provides STI diagnosis and treatment in an impoverished, peri-urban community outside of Cape Town, South Africa. METHODS: The researchers and local health administrators collaborated to investigate the cause of the poor test performance and make necessary corrections. The clinic changed the brand of rapid test being used and later introduced quality improvement measures. Observations were made of the clinic staff as they administered rapid HIV tests to real patients. Estimated testing sensitivity was calculated as the number of rapid HIV test positive individuals detected by the clinic divided by this number plus the number of PCR positive, highly reactive 3rd generation ELISA patients identified among those who were rapid test negative at the clinic. RESULTS: In the period of five months after the clinic made the switch of rapid HIV tests, estimated sensitivity improved to 93.5% (95% CI [86.5%-97.6%]), during which time observations of counselors administering tests at the clinic found poor adherence to the recommended testing protocol. Quality improvement measures were implemented and estimated sensitivity rose to 95.1% (95% CI [83.5%-99.4%]) during the final two months of full observation. CONCLUSIONS: Poor testing procedure in the field can lead to exceedingly low levels of rapid HIV test sensitivity, making it imperative that stringent quality control measures are implemented where they do not already exist. Certain brands of rapid-testing kits may perform better than others when faced with sub-optimal use.

Injectable-free regimens containing bedaquiline, delamanid, or both for adolescents with rifampicin-resistant tuberculosis in Khayelitsha, South Africa.

BACKGROUND: Limited data exist on the use of bedaquiline and delamanid in adolescents with rifampicin-resistant tuberculosis (RR-TB). We describe RR-TB treatment of adolescents (10-19 years) with injectable-free regimens containing these drugs in Khayelitsha, South Africa. METHODS: This retrospective study included adolescents initiating injectable-free RR-TB treatment regimens containing bedaquiline and/or delamanid from February 2015 to June 2018. We report adverse events (AEs) of interest, sputum culture conversion (SCC), and final end-of-treatment outcomes. FINDINGS: Twenty-two patients were included; median age at treatment initiation was 17 years (interquartile range [IQR] 15-18), and six (27%) were HIV-positive (median CD4 count 191 cells/mm3 [IQR 157-204]). Eight (36%) patients had RR-TB with fluoroquinolone resistance; ten (45%), eight (36%), and four (18%) patients received regimens containing bedaquiline, delamanid, or the combination of bedaquiline and delamanid, respectively. The median durations of exposure to bedaquiline and delamanid were 5·6 (IQR 5·5-8·4) and 9·4 (IQR 5·9-14·4) months, respectively. There were 49 AEs of interest which occurred in 17 (77%) patients. Fourteen (64%) patients had pulmonary TB with positive sputum cultures at bedaquiline and/or delamanid initiation; among these SCC at month 6 was 79%. Final end-of-treatment outcomes for the 22 adolescent were: 17 (77%) successfully treated, two (9%) lost-to-follow-up, two (9%) treatment failed, and one (5%) died. INTERPRETATION: This study found that injectable-free regimens containing bedaquiline and/or delamanid in a programmatic setting were effective and well tolerated in adolescents and should be routinely provided for RR-TB treatment in this age group as recommended by the World Health Organisation.

Incidence of Tuberculosis Among HIV-Positive Individuals Initiating Antiretroviral Treatment at Higher CD4 Counts in the HPTN 071 (PopART) Trial in South Africa.

INTRODUCTION: Antiretroviral treatment (ART) guidelines recommend life-long ART for all HIV-positive individuals. This study evaluated tuberculosis (TB) incidence on ART in a cohort of HIV-positive individuals starting ART regardless of CD4 count in a programmatic setting at 3 clinics included in the HPTN 071 (PopART) trial in South Africa. METHODS: A retrospective cohort analysis of HIV-positive individuals aged ≥18 years starting ART, between January 2014 and November 2015, was conducted. Follow-up was continued until 30 May 2016 or censored on the date of (1) incident TB, (2) loss to follow-up from HIV care or death, or (3) elective transfer out; whichever occurred first. RESULTS: The study included 2423 individuals. Median baseline CD4 count was 328 cells/µL (interquartile range 195-468); TB incidence rate was 4.41/100 person-years (95% confidence interval [CI]: 3.62 to 5.39). The adjusted hazard ratio of incident TB was 0.27 (95% CI: 0.12 to 0.62) when comparing individuals with baseline CD4 >500 and ≤500 cells/µL. Among individuals with baseline CD4 count >500 cells/µL, there were no incident TB cases in the first 3 months of follow-up. Adjusted hazard of incident TB was also higher among men (adjusted hazard ratio 2.16; 95% CI: 1.41 to 3.30). CONCLUSIONS: TB incidence after ART initiation was significantly lower among individuals starting ART at CD4 counts above 500 cells/µL. Scale-up of ART, regardless of CD4 count, has the potential to significantly reduce TB incidence among HIV-positive individuals. However, this needs to be combined with strengthening of other TB prevention strategies that target both HIV-positive and HIV-negative individuals.

DOT or SAT for Rifampicin-resistant tuberculosis? A non-randomized comparison in a high HIV-prevalence setting.

BACKGROUND: Daily directly-observed therapy (DOT) is recommended for rifampicin-resistant tuberculosis (RR-TB) patients throughout treatment. We assessed the impact of self-administered treatment (SAT) in a South African township with high rates of RR-TB and HIV. METHODS: Community-supported SAT for patients who completed the intensive phase was piloted in five primary care clinics in Khayelitsha. We compared final treatment outcomes among RR-TB patients initiating treatment before (standard-of-care (SOC)-cohort, January 2010-July 2013) and after the implementation of the pilot (SAT-cohort, January 2012-December 2014). All patients with outcomes before January 1, 2017 were considered in the analysis of outcomes. RESULTS: One-hundred-eighteen patients in the SOC-cohort and 174 patients in the SAT-cohort had final RR-TB treatment outcomes; 70% and 73% were HIV-co-infected, respectively. The proportion of patients with a final outcome of loss to follow-up (LTFU) did not differ whether treated in the SOC (25/118, 21.2%) or SAT-cohort (31/174, 17.8%) (P = 0.47). There were no significant differences in the time to 24-month LTFU among HIV-infected and uninfected patients (HR 0.90, 95% CI: 0.51-1.6, P = 0.71), or among patients enrolled in the SOC-cohort versus the SAT-cohort (HR 0.83, 95% CI: 0.49-1.4, P = 0.50) who received at least 6-months of RR-TB treatment. CONCLUSION: The introduction of SAT during the continuation phase of RR-TB treatment does not adversely affect final RR-TB treatment outcomes in a high TB and HIV-burden setting. This differentiated, patient-centred model of care could be considered in RR-TB programmes to decrease the burden of DOT on patients and health facilities.

Outcomes from the implementation of a counselling model supporting rapid antiretroviral treatment initiation in a primary healthcare clinic in Khayelitsha, South Africa.

BACKGROUND: Lengthy antiretroviral treatment (ART) preparation contributes to high losses to care between communicating ART eligibility and initiating ART. To address this shortfall, Médecins Sans Frontières implemented a revised approach to ART initiation counselling preparation (integrated for TB co-infected patients), shifting the emphasis from pre-initiation sessions to addressing common barriers to adherence and strengthening post-initiation support in a primary healthcare facility in Khayelitsha, South Africa. METHODS: An observational cohort study was conducted using routinely collected data for all ART-eligible patients attending their first counselling session between 23 July 2012 and 30 April 2013 to assess losses to care prior to and post ART initiation. Viral load completion and suppression rates of those retained on ART were also calculated. RESULTS: Overall, 449 patients enrolled in the study, of whom 3.6% did not return to the facility to initiate ART. Of those who were initiated, 96.7% were retained at their first ART refill visit and 85.9% were retained 6 months post ART initiation. Of those retained, 80.2% had a viral load taken within 6 months of initiating ART, with 95.4% achieving viral load suppression. CONCLUSIONS: Adapting counselling to enable rapid ART initiation is feasible and has the potential to reduce losses to care prior to ART initiation without increasing short-term losses thereafter or compromising patient adherence.

Impact of Decentralized Care and the Xpert MTB/RIF Test on Rifampicin-Resistant Tuberculosis Treatment Initiation in Khayelitsha, South Africa.

Background. Globally, case detection and treatment access are poor for rifampicin-resistant tuberculosis (RR-TB). The Xpert MTB/RIF test has the potential to increase detection and reduce time to treatment (TTT). However, these benefits are dependent on health system capacity to provide treatment. Methods. We retrospectively assessed the impact of Xpert on treatment initiation and TTT in the context of decentralized RR-TB care in Khayelitsha, Cape Town, using routine programmatic data. Community-based treatment was introduced progressively from 2008. Before 2007, diagnosis relied on phenotypic resistance (culture). During 2007-2008, the line probe assay (LPA) was introduced, followed by Xpert in 2012. Results. Before decentralization (2003-2006), median TTT was 71 days (interquartile range [IQR], 49-134; n = 158). The LPA introduction during 2007-2008 was associated with reduced median TTT from 76 to 50 days (P < .0001, n = 257). Between January 2009 and June 2013, 938 RR-TB cases were diagnosed (74% human immunodeficiency virus [HIV]-infected). Decentralization during 2008-2011 was associated with declining TTT (P < .0001, test for trend), a decline to 28 days in 2011 (IQR, 16-40; n = 173). Xpert was associated with a further reduction to 8 days in 2013 (IQR, 5-25; n = 89; P < .0001). Treatment initiation remained unchanged with Xpert and was lower among HIV-infected (2010-2013); 87.9% (445 of 506) compared with 96.9% (188 of 194) for HIV-uninfected (P < .0001) patients. Conclusions. Improved case detection and rapid treatment initiation are required to interrupt transmission and reduce mortality. In this setting, decentralization was associated with high treatment initiation and reduced TTT. Xpert implementation significantly enhanced the reduction in TTT and has the potential to reduce transmission.

Loss from treatment for drug resistant tuberculosis: risk factors and patient outcomes in a community-based program in Khayelitsha, South Africa.

BACKGROUND: A community based drug resistant tuberculosis (DR-TB) program has been incrementally implemented in Khayelitsha, a high HIV and TB burden community in South Africa. We investigated loss from treatment (LFT), and post treatment outcomes of DR-TB patients in this setting. METHODOLOGY: LFT, defined as interruption of treatment for ≥2 consecutive months was assessed among patients initiating DR-TB treatment for the first time between January 2009 and July 2011. Patients were traced through routine data sources to identify those who subsequently restarted treatment and those who died. Additional information on patient status and survival after LTF was obtained from community DR-TB counselors and from the national death registry. Post treatment outcomes were observed until July 2013. RESULTS: Among 452 patients initiating treatment for the first time within the given period, 30% (136) were LFT, with 67% retention at 18 months. Treatment was restarted in 27 (20%) patients, with additional resistance recorded in 2/25 (8%), excluding two with presumed DR-TB. Overall, 34 (25%) patients died, including 11 who restarted treatment. Males and those in the age category 15-25 years had a greater hazard of LFT; HR 1.93 (95% CI 1.35-2.75), and 2.43 (95% CI 1.52-3.88) respectively. Older age (>35 years) was associated with a greater hazard of death; HR 3.74 (1.13- 12.37) post treatment. Overall two-year survival was 62%. It was lower (45%) in older patients, and was 92% among those who received >12 months treatment. CONCLUSION: LFT was high, occurred throughout the treatment period and was particularly high among males and those aged 15-25 years. Overall long term survival was poor. High rates of LFT should however not preclude scale up of community based care given its impact in increasing access to treatment. Further research is needed to support retention of DR-TB patients on treatment, even within community based treatment programs.

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success.

SETTING: Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection. OBJECTIVE: To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes. DESIGN: A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation. RESULTS: Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count ≤100 (aHR 2.1, CI 1.0-4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1-5.4). CONCLUSIONS: Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

Clinical mentorship of nurse initiated antiretroviral therapy in Khayelitsha, South Africa: a quality of care assessment.

INTRODUCTION: To combat the AIDS epidemic and increase HIV treatment access, the South African government implemented a nurse-based, doctor-supported model of care that decentralizes administration of antiretroviral treatment (ART) for HIV positive patients through nurse initiated and managed ART. Médecins Sans Frontières (MSF) implemented a mentorship programme to ensure successful task-shifting, subsequently assessing the quality of clinical care provided by nurses. METHODS: A before-after cross-sectional study was conducted on nurses completing the mentorship programme in Khayelitsha, South Africa, from February 2011-September 2012. Routine clinical data from 229 patient folders and 21 self-assessment questionnaires was collected to determine the number of patients initiated on ART by nurses; quality of ART management before-after mentorship; patient characteristics for doctor and nurse ART initiations; and nurse self-assessments after mentorship. RESULTS: Twenty one nurses were authorized by one nurse mentor with one part-time medical officer's support, resulting in nurses initiating 77% of ART eligible patients. Improvements in ART management were found for drawing required bloods (91% vs 99%, p = 0.03), assessing adherence (50% vs 78%, p<0.001) and WHO staging (63% vs 91%, p<0.001). Nurse ART initiation indicators were successfully completed at 95-100% for 11 of 16 indicators: clinical presentation; patient weight; baseline blood work (CD4, creatinine, haemoglobin); STI screening; WHO stage, correlating medical history; medications prescribed appropriately; ART start date; and documented return date. Doctors initiated more patients with TB/HIV co-infection and WHO Stage 3 and 4 disease than nurses. Nurse confidence improved for managing HIV-infected children and pregnant women, blood result interpretation and long-term side effects. CONCLUSIONS: Implementation of a clinical mentorship programme in Khayelitsha led to nurse initiation of a majority of eligible patients, enabling medical officers to manage complex cases. As mentorship can increase clinical confidence and enhance professional development, it should be considered essential for universal ART access in resource limited settings.