Optimised electronic patient records to improve clinical monitoring of HIV-positive patients in rural South Africa (MONART trial): study protocol for a cluster-randomised trial.

BACKGROUND: There is poor viral load monitoring (VLM) and inadequate management of virological failure in HIV-positive individuals on antiretroviral therapy in rural KwaZulu-Natal, South Africa. This could be contributing to increasing HIV drug resistance in the setting. This study aims to investigate the clinical and process impediments in VLM within the health system and to evaluate a quality improvement package (QIP) to address the identified gaps. The QIP comprises (i) a designated viral load champion responsible for administrative management and triaging of viral load results (ii) technological enhancement of the routine clinic-based Three Interlinked Electronic Register (TIER.Net) to facilitate daily automatic import of viral load results from the National Health Service Laboratory to TIER.Net (iii) development of a dashboard system to support VLM. METHODS/DESIGN: The study will evaluate the effectiveness of the QIP compared to current care for improving VLM and virological suppression using an effectiveness implementation hybrid type 3 design. This will use a cluster-randomised design with the primary healthcare clinics as the unit of randomisation with ten clinics randomised in a 1:1 ratio to either the intervention or control arm. We will enrol 150 HIV-positive individuals who had been on ART for ≥ 12 months from each of the ten clinics (750 in 5 intervention clinics vs. 750 in 5 control clinics) and follow them up for a period of 12 months. The primary outcome is the proportion of all patients who have a viral load (VL) measurement and are virally suppressed (composite outcome) after 12 months of follow up. Secondary outcomes during follow up include proportion of all patients with at least one documented VL in TIER.Net, proportion with VL ≥ 50 copies/mL, proportion with VL ≥ 1000 copies/mL (virological failure) and subsequent switch to second-line ART. DISCUSSION: We aim to provide evidence that a staff-centred quality improvement package, designated viral load monitoring champion, and augmentation of TIER.Net with a dashboard system will improve viral load monitoring and lead to improved virological suppression. TRIAL REGISTRATION: This trial is registered on ClinicalTrials.gov on 8 Oct 2021. Identifier: NCT05071573; https://clinicaltrials.gov/ct2/show/NCT05071573?term=NCT05071573&draw=2&rank=1.

The Continuing Burden of Advanced HIV Disease Over 10 Years of Increasing Antiretroviral Therapy Coverage in South Africa.

Background: Antiretroviral treatment (ART) has been massively scaled up to decrease human immunodeficiency virus (HIV)-related morbidity, mortality, and HIV transmission. However, despite documented increases in ART coverage, morbidity and mortality have remained substantial. This study describes trends in the numbers and characteristics of patients with very advanced HIV disease in the Western Cape, South Africa. Methods: Annual cross-sectional snapshots of CD4 distributions were described over 10 years, derived from a province-wide cohort of all HIV patients receiving CD4 cell count testing in the public sector. Patients with a first CD4 count <50 cells/µL in each year were characterized with respect to prior CD4 and viral load testing, ART access, and retention in ART care. Results: Patients attending HIV care for the first time initially constituted the largest group of those with CD4 count <50 cells/µL, dropping proportionally over the decade from 60.9% to 26.7%. By contrast, the proportion who were ART experienced increased from 14.3% to 56.7%. In patients with CD4 counts <50 cells/µL in 2016, 51.8% were ART experienced, of whom 76% could be confirmed to be off ART or had recent viremia. More than half who were ART experienced with a CD4 count <50 cells/µL in 2016 were men, compared to approximately one-third of all patients on ART in the same year. Conclusions: Ongoing HIV-associated morbidity now results largely from treatment-experienced patients not being in continuous care or not being fully virologically suppressed. Innovative interventions to retain ART patients in effective care are an essential priority for the ongoing HIV response.

Contemporary disengagement from antiretroviral therapy in Khayelitsha, South Africa: A cohort study.

BACKGROUND: Retention in care is an essential component of meeting the UNAIDS "90-90-90" HIV treatment targets. In Khayelitsha township (population ~500,000) in Cape Town, South Africa, more than 50,000 patients have received antiretroviral therapy (ART) since the inception of this public-sector program in 2001. Disengagement from care remains an important challenge. We sought to determine the incidence of and risk factors associated with disengagement from care during 2013-2014 and outcomes for those who disengaged. METHODS AND FINDINGS: We conducted a retrospective cohort study of all patients ≥10 years of age who visited 1 of the 13 Khayelitsha ART clinics from 2013-2014 regardless of the date they initiated ART. We described the cumulative incidence of first disengagement (>180 days not attending clinic) between 1 January 2013 and 31 December 2014 using competing risks methods, enabling us to estimate disengagement incidence up to 10 years after ART initiation. We also described risk factors for disengagement based on a Cox proportional hazards model, using multiple imputation for missing data. We ascertained outcomes (death, return to care, hospital admission, other hospital contact, alive but not in care, no information) after disengagement until 30 June 2015 using province-wide health databases and the National Death Registry. Of 39,884 patients meeting our eligibility criteria, the median time on ART to 31 December 2014 was 33.6 months (IQR 12.4-63.2). Of the total study cohort, 592 (1.5%) died in the study period, 1,231 (3.1%) formally transferred out, 987 (2.5%) were silent transfers and visited another Western Cape province clinic within 180 days, 9,005 (22.6%) disengaged, and 28,069 (70.4%) remained in care. Cumulative incidence of disengagement from care was estimated to be 25.1% by 2 years and 50.3% by 5 years on ART. Key factors associated with disengagement (age, male sex, pregnancy at ART start [HR 1.58, 95% CI 1.47-1.69], most recent CD4 count) and retention (ART club membership, baseline CD4) after adjustment were similar to those found in previous studies; however, notably, the higher hazard of disengagement soon after starting ART was no longer present after adjusting for these risk factors. Of the 9,005 who disengaged, the 2 most common initial outcomes were return to ART care after 180 days (33%; n = 2,976) and being alive but not in care in the Western Cape (25%; n = 2,255). After disengagement, a total of 1,459 (16%) patients were hospitalized and 237 (3%) died. The median follow-up from date of disengagement to 30 June 2015 was 16.7 months (IQR 11-22.4). As we included only patient follow-up from 2013-2014 by design in order to maximize the generalizability of our findings to current programs, this limited our ability to more fully describe temporal trends in first disengagement. CONCLUSIONS: Twenty-three percent of ART patients in the large cohort of Khayelitsha, one of the oldest public-sector ART programs in South Africa, disengaged from care at least once in a contemporary 2-year period. Fifty-eight percent of these patients either subsequently returned to care (some "silently") or remained alive without hospitalization, suggesting that many who are considered "lost" actually return to care, and that misclassification of "lost" patients is likely common in similar urban populations. A challenge to meeting ART retention targets is developing, testing, and implementing program designs to target mobile populations and retain them in lifelong care. This should be guided by risk factors for disengagement and improving interlinkage of routine information systems to better support patient care across complex care platforms.

A comparison of linkage to HIV care after provider-initiated HIV testing and counselling (PITC) versus voluntary HIV counselling and testing (VCT) for patients with sexually transmitted infections in Cape Town, South Africa.

BACKGROUND: We examined linkage to care for patients with sexually transmitted infection who were diagnosed HIV-positive via the provider-initiated HIV testing and counselling (PITC) approach, as compared to the voluntary counselling and testing (VCT) approach, as little is known about the impact of expanded testing strategies on linkage to care. METHODS: In a controlled trial on PITC (Cape Town, 2007), we compared HIV follow-up care for a nested cohort of 930 HIV-positive patients. We cross-referenced HIV testing and laboratory records to determine access to CD4 and viral load testing as primary outcomes. Secondary outcomes were HIV immune status and time taken to be linked to HIV care. Logistic regression was performed to analyse the difference between arms. RESULTS: There was no difference in the main outcomes of patients with a record of CD4 testing (69.9% in the intervention, 65.2% in control sites, OR 0.82 (CI: 0.44-1.51; p = 0.526) and viral load testing (14.9% intervention versus 10.9% control arm; OR 0.69 (CI: 0.42-1.12; p = 0.131). In the intervention arm, ART-eligible patients (based on low CD4 test result), accessed viral load testing approximately 2.5 months sooner than those in the control arm (214 days vs. 288 days, HR: 0.417, 95% CI: 0.221-0.784; p = 0.007). CONCLUSION: The PITC intervention did not improve linkage to CD4 testing, but shortened the time to viral load testing for ART-eligible patients. Major gaps found in follow-up care across both arms, indicate the need for more effective linkage-to-HIV care strategies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93692532.

Effect of antiretroviral therapy care interruptions on mortality in children living with HIV.

OBJECTIVE: To evaluate the characteristics and outcomes of HIV-infected children that have care interruptions, during which the child's health status and use of medication is unknown. DESIGN: We included data on children initiating ART between 2004 and 2016 at less than 16 years old at 16 International Epidemiologic Databases to Evaluate AIDS Southern Africa cohorts. Children were classified as loss to follow up (LTFU) if they had not attended clinic for more than 180 days. Children had a care interruption if they were classified as LTFU, and subsequently returned to care. Children who died within 180 days of ART start were excluded. METHODS: The main outcome was all cause mortality. Two exposed groups were considered: those with a first care interruption within the first 6 months on ART, and those with a first care interruption after 6 months on ART. Adjusted hazard ratios were determined using a Cox regression model. RESULTS: Among 53 674 children included, 23 437 (44%) had a care interruption, of which 10 629 (20%) had a first care interruption within 6 months on ART and 12 808 (24%) had a first care interruption after 6 months on ART. Increased mortality was associated with a care interruption within 6 months on ART [adjusted hazard ratio (AHR) = 1.52, 95% CI 1.12-2.04] but not with a care interruption after 6 months on ART (AHR = 1.05, 95% CI 0.77-1.44). CONCLUSION: The findings suggest that strengthening retention of children in care in the early period after ART initiation is critical to improving paediatric ART outcomes.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Risk factors for and clinical characteristics of severe hyperlactataemia in patients receiving antiretroviral therapy: a case-control study.

BACKGROUND: Symptomatic hyperlactataemia and lactic acidosis (SHLA) are potentially life-threatening complications associated with stavudine (d4T), an antiretroviral therapy (ART) drug widely used in developing countries. METHODS: Cases comprised all symptomatic patients with measured lactates >or= 5 mmol/L referred to a South African hospital between August 2003 and November 2005. Matched controls were selected according to facility and duration on ART. RESULTS: Seventy-one cases and 142 controls were included in the study. The majority of cases presented between 6 and 18 months on ART. Female sex [adjusted odds ratio (AOR) 23.4; 95% confidence interval (CI) 4.0-136.6], a baseline weight between 60 and 75 kg (AOR 4.5; 95% CI 1.4-14.1) or, in particular, >or= 75 kg (AOR 19.4; 95% CI 4.1-82.5) at ART initiation and gaining >or= 6 kg in the first 3 months on therapy (AOR 3.5; 95% CI 1.3-9.5) were independent risk factors identifying patients who may subsequently develop SHLA. Weight loss of >or= 2 kg (AOR 6.1; 95% CI 2.0-18.3), a rise in alanine aminotransferase (ALT) >or= 10 U/L (AOR 3.1; 95% CI 1.1-8.9), the presence of at least one of three major symptoms (vomiting, nausea and abdominal pains) of SHLA (AOR 12.6; 95% CI 3.3-47.2) and peripheral neuropathy (AOR 3.4; 95% CI 1.1-9.8) were the clinical parameters that were most able to identify patients with early manifestations of SHLA. CONCLUSIONS: This is the first case-control study for SHLA in Southern Africa. Given these findings, we advise that stavudine is avoided in overweight women. Weight loss, a rise in ALT, peripheral neuropathy and/or gastrointestinal symptoms should prompt healthcare workers to assess for SHLA, especially at between 6 and 18 months on ART.

Reduced referral and case fatality rates for severe symptomatic hyperlactataemia in a South African public sector antiretroviral programme: a retrospective observational study.

BACKGROUND: Interventions to promote prevention and earlier diagnosis of severe symptomatic hyperlactataemia (SHL) were implemented in the Western Cape provincial antiretroviral programme (South Africa) from 2004. Interventions included clinician education, point-of-care lactate meters, switch from stavudine to zidovudine in high risk patients and stavudine dose reduction. This study assessed trends in referral rate, severity at presentation and case fatality rate for severe SHL. METHODS: Retrospective study of severe SHL cases diagnosed at a referral facility from 1 January 2003 to 31 December 2008. Severe SHL was defined as patients with compatible symptoms and serum lactate >/= 5 mmol/l attributable to antiretroviral therapy (ART). Cumulative ART exposure at referring ART clinics was used to calculate referral rates. RESULTS: There were 254 severe SHL cases. The referral rate (per thousand patient years [py] ART exposure) peaked in 2005 (20.4/1000py), but fell to 1.3/1000py by 2008 (incidence rate ratio [IRR] = 0.07, 95%CI 0.04-0.11). In 2003, 66.7% of cases presented with a standard bicarbonate (SHCO3) level <15 mmol/l, but this fell to 12.5% by 2008 (p for trend < 0.001). Case fatality rate fell from a peak of 33.3% in 2004 to 0% in 2008 (p for trend = 0.002). CONCLUSIONS: These trends suggest the interventions were associated with reduced referral, less severe metabolic acidosis at presentation and improved survival.

Population-wide differentials in HIV service access and outcomes in the Western Cape for men as compared to women, South Africa: 2008 to 2018: a cohort analysis.

INTRODUCTION: Few studies have systematically described population-level differences comparing men and women across the continuum of routine HIV care. This study quantifies differentials in HIV care, treatment and mortality outcomes for men and women over time in South Africa. METHODS: We analysed population-wide linked anonymized data, including vital registration linkage, for the Western Cape Province, from the time of first CD4 count. Three antiretroviral therapy guideline eligibility periods were defined: 1 January 2008 to 31 July 2011 (CD4 cell count <200 cells/µL), 1 August 2011 to 31 December 2014 (<350 cells/µL), 1 January 2015 to 31 August 2016 (<500 cells/µL). We estimated care uptake based on service attendance, and modelled associations for men and women with ART initiation and overall, pre-ART and ART mortality. Separate Cox proportional hazard models were built for each outcome and eligibility period, adjusted for tuberculosis, pregnancy, CD4 count and age. RESULTS: Adult men made up 49% of the population and constituted 37% of those living with HIV. In 2009, 46% of men living with HIV attended health services, rising to 67% by 2015 compared to 54% and 77% of women respectively. Men contributed <35% of all CD4 cell counts over 10 years and presented with more advanced disease (39% of all first presentation CD4 cell counts from men were <200 cells/µL compared to 25% in women). ART access was lower in men compared to women (AHR 0.79 (0.77 to 0.80) summarized for Period 2) over the entire study). Mortality was greater in men irrespective of ART (AHR 1.08 (1.01 to 1.16) Period 3) and after ART start (AHR 1.15 (1.05 to 1.20) Period 3) with mortality differences decreasing over time. CONCLUSIONS: Compared to women, men presented with more advanced disease, were less likely to attend health care services annually, were less likely to initiate ART and had higher mortality overall and while receiving ART care. People living with HIV were more likely to initiate ART if they had acute reasons to access healthcare beyond HIV, such as being pregnant or being co-infected with tuberculosis. Our findings point to missed opportunities for improving access to and outcomes from interventions for men along the entire HIV cascade.

A longitudinal analysis of the completeness of maternal HIV testing, including repeat testing in Cape Town, South Africa.

INTRODUCTION: The virtual elimination of mother-to-child transmission of HIV cannot be achieved without complete maternal HIV testing. The World Health Organization recommends that women in high HIV prevalent settings repeat HIV testing in the third trimester, and at delivery or directly thereafter. The Western Cape Province (South Africa) prevention of mother-to-child transmission (PMTCT) guidelines recommend a repeat maternal HIV test between 32 and 34 weeks gestation and at delivery in addition to testing at the first antenatal visit (ideally <20 weeks gestation). There are few published longitudinal studies on the uptake of initial and repeated maternal HIV testing programmes in sub-Saharan Africa. We aimed to investigate the implementation of initial and repeat maternal HIV testing guidelines in Cape Town, South Africa. METHODS: Between 2013 and 2016 we established an electronic PMTCT register that consolidated routine data from a primary healthcare facility and its secondary and tertiary referral sites in Cape Town. This provided a longitudinal record for each participant, from first antenatal visit to delivery. Utilizing these data, we conducted a retrospective analysis investigating the completeness of maternal HIV testing according to the PMTCT HIV testing guidelines in Cape Town, and predictors of complete testing, from 2014 to 2016. RESULTS: Among 8558 enrolled pregnant women, 7213 (84%) were not known to be HIV positive at their first visit and thus eligible for HIV testing; 91% of them received ≥1 HIV test during pregnancy/delivery. Testing at the first visit was 98% among the 85% of women who attended antenatal care. Among women eligible to receive all three recommended HIV tests, only 11% achieved all three tests. Delivery HIV testing completion among all women without an HIV-positive diagnosis was 23%. HIV prevalence at delivery was 21% and HIV incidence between first visit and delivery in those with ≥2 HIV tests was 0.2%. Women who enrolled after 2014 were more likely to receive the three recommended tests (aOR: 1.41; 95% CI: 1.10 to 1.81) and retest at delivery (aOR: 1.20; 95% CI: 1.05 to 1.39). CONCLUSIONS: Implementation of maternal HIV testing in Cape Town improved between 2014 and 2016 but major gaps remain, particularly at delivery.

Severe hyperlactataemia complicating stavudine first-line antiretroviral therapy in South Africa.

BACKGROUND: In the public sector antiretroviral therapy (ART) programme in South Africa the standardized first-line regimen includes stavudine (d4T). Severe symptomatic hyperlactataemia (SHL) is a potentially life-threatening complication of d4T. METHODS: GF Jooste Hospital is a referral centre for six ART clinics. We retrospectively reviewed cases referred with lactate levels > or =5 mmol/l that were attributed to nucleoside reverse transcriptase inhibitors from August 2003 to November 2005. We calculated cumulative ART exposure in patients attending these clinics to derive a referral rate. RESULTS: In total, 75 patients were referred with severe SHL (71 female). All had been on d4T and on ART for a median of 10 months. The referral rate for severe SHL was 17.5 cases per 1,000 patient-years. In 53 patients (71%), lactic acidosis (standard bicarbonate [SHCO3] <20 mmol/l) was confirmed, resulting in a referral rate of 12.3 cases per 1,000 patient-years. Twelve patients (16%) died during acute admission (< or =30 days). SHCO3 <15 mmol/l and pH < 7.2 were the only factors associated with acute mortality (odds ratio [OR] 22.5, 95% confidence interval [CI] 2.8-1,045.7 and OR 13.9, 95% CI 2.7-86.9, respectively). A total of 30 less severe cases were rechallenged with zidovudine without recurrence of SHL. CONCLUSIONS: This study confirms a high incidence of severe SHL in Africa, which has been shown in previous studies. Rechallenge with zidovudine in less severe cases was found to be safe.

Antiretroviral therapy and early mortality in South Africa.

OBJECTIVE: To describe province-wide outcomes and temporal trends of the Western Cape Province antiretroviral treatment (ART) programme 5 years since inception, and to demonstrate the utility of the WHO monitoring system for ART. METHODS: The treatment programme started in 2001 through innovator sites. Rapid scaling-up of ART provision began early in 2004, located predominantly in primary-care facilities. Data on patients starting ART were prospectively captured into facility-based registers, from which monthly cross-sectional activity and quarterly cohort reports were aggregated. Retention in care, mortality, loss to follow-up and laboratory outcomes were calculated at 6-monthly durations on ART. FINDINGS: By the end of March 2006, 16 234 patients were in care. The cohort analysis included 12 587 adults and 1709 children. Women accounted for 70% of adults enrolled. After 4 and 3 years on ART respectively, 72.0% of adults (95% confidence interval, CI: 68.0-75.6) and 81.5% (95% CI: 75.7-86.1) of children remained in care. The percentage of adults starting ART with CD4 counts less than 50 cells/microl fell from 51.3% in 2001 to 21.5% in 2005, while mortality at 6 months fell from 12.7% to 6.6%, offset in part by an increase in loss to follow-up (reaching 4.7% at 6 months in 2005). Over 85% of adults tested had viral loads below 400 copies/ml at 6-monthly durations until 4 years on ART. CONCLUSION: The location of care in primary-care sites in this programme was associated with good retention in care, while the scaling-up of ART provision was associated with reduced early mortality.

Provision of antiretroviral therapy to children within the public sector of South Africa.

The South African Department of Health has embraced the primary health care approach in the provision of antiretroviral therapy (ART) to children. This paper compares clinical outcomes of children treated at primary healthcare clinics, district hospitals, and secondary and tertiary hospitals. A retrospective review of routine data captured by the provincial antiretroviral monitoring system was completed. Simplified cohort analysis was used to determine the cumulative incidence of baseline characteristics and outcomes. Data on 1741 children started at level 2 & 3, level 1 and primary healthcare clinic facilities between April 2004 and April 2006 were analysed. Kaplan-Meier survival estimates for these groups were 0.88 (95% CI 0.86-0.90), 0.94 (95% CI 0.89-0.97) and 0.94 (95% CI 0.89-0.96) at 12 months of ART, respectively, on intention-to-treat analysis. The overall cumulative proportion of children with a suppressed viral load was 73% (95% CI 69-77%) at 12 months of ART. There was no significant difference in viral load suppression rates between the three groups. This study confirms the feasibility of providing antiretrovirals at all levels of the healthcare service in the Western Cape. The higher death rates at level 2 & 3 facilities are most likely due to recruitment of sicker patients at this level.

Neonatal and infant diagnostic HIV-PCR uptake and associations during three sequential policy periods in Cape Town, South Africa: a longitudinal analysis.

INTRODUCTION: To strengthen the early infant diagnosis (EID) programmes and timeously identify and treat HIV-infected infants, birth HIV-PCR for some/all infants has been recommended in the Western Cape, South Africa since 2014. Operational data on the implementation of such programmes in low- and middle-income countries are limited. METHODS: Utilizing the electronic records platform at primary care facilities, we developed an electronic register which consolidated obstetric and HIV-related data, allowing us to track a cohort of HIV-infected/exposed mother/infant dyads longitudinally from antenatal care through delivery to infant HIV-PCR. We assessed guideline implementation and impact on EID of three sequential EID policies in a referral chain of facilities in Cape Town (primary-tertiary care). Birth HIV-PCR was indicated in period 1 if symptomatic; period 2 if meeting high-risk criteria for transmission; and period 3 for all HIV-exposed neonates. RESULTS: We enrolled 2012 HIV-exposed infants; 89.2% had at least one HIV-PCR at any point. The majority of birth tests were performed in hospital versus primary care regardless of policy period. Almost half of all infants (47.9%) had at least one high-risk criterion for vertical infection; of these, 39.7% had a birth test. Infants with more risk factors were more likely to have birth EID. Receipt of a birth HIV-PCR significantly reduced the likelihood of receiving a follow-up test at six to ten weeks, even after adjusting for potential confounders (aOR 0.18 (0.12 to 0.26)). The proportion of infants tested at six to ten weeks old dropped from 92.9% (period 1) to 80.2% in period 3 and those receiving birth HIV-PCR increased, peaking at 67.4% during period 3. The proportion of positive birth tests was highest (2.9%) when birth tests were restricted to infants meeting high-risk criteria, with a low proportion positive for the first time at six to ten weeks. During period 3, the proportion positive at six to ten weeks was high (2.4%), highlighting the importance of follow-up to detect intrapartum and early postpartum infections. CONCLUSIONS: Over all policy periods, EID guidelines were incompletely implemented across all levels of care but especially in primary care. Birth HIV-PCR reduced return for follow-up testing, such follow-up testing is critical for the effectiveness of the programme.

Implementation and Operational Research: Evaluation of a Public-Sector, Provider-Initiated Cryptococcal Antigen Screening and Treatment Program, Western Cape, South Africa.

BACKGROUND: Screening for serum cryptococcal antigen (CrAg) may identify those at risk for disseminated cryptococcal disease (DCD), and preemptive fluconazole treatment may prevent progression to DCD. In August 2012, the Western Cape Province (WC), South Africa, adopted provider-initiated CrAg screening. We evaluated the implementation and effectiveness of this large-scale public-sector program during its first year, September 1, 2012-August 31, 2013. METHODS: We used data from the South African National Health Laboratory Service, WC provincial HIV program, and nationwide surveillance data for DCD. We assessed the proportion of eligible patients screened for CrAg (CrAg test done within 30 days of CD4 date) and the prevalence of CrAg positivity. Incidence of DCD among those screened was compared with those not screened. RESULTS: Of 4395 eligible patients, 26.6% (n = 1170) were screened. The proportion of patients screened increased from 15.9% in September 2012 to 36.6% in August 2013. The prevalence of positive serum CrAg was 2.1%. Treatment data were available for 13 of 24 CrAg-positive patients; 9 of 13 were treated with fluconazole. Nine (0.8%) incident cases of DCD occurred among the 1170 patients who were screened for CrAg vs. 49 (1.5%) incident cases among the 3225 patients not screened (P = 0.07). CONCLUSIONS: Relatively few eligible patients were screened under the WC provider-initiated CrAg screening program. Unscreened patients were nearly twice as likely to develop DCD. CrAg screening can reduce the burden of DCD, but needs to be implemented well. To improve screening rates, countries should consider laboratory-based reflexive screening when possible.

A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings.

The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART, tuberculosis and mother and child health services can be an efficient approach to ensuring system-wide harmonization and accurate monitoring of services, including long term retention in care, during the scale-up of electronic monitoring solutions.

Seven-year experience of a primary care antiretroviral treatment programme in Khayelitsha, South Africa.

OBJECTIVES: We report on outcomes after 7 years of a community-based antiretroviral therapy (ART) programme in Khayelitsha, South Africa, with death registry linkages to correct for mortality under-ascertainment. DESIGN: This is an observational cohort study. METHODS: Since inception, patient-level clinical data have been prospectively captured on-site into an electronic patient information system. Patients with available civil identification numbers who were lost to follow-up were matched with the national death registry to ascertain their vital status. Corrected mortality estimates weighted these patients to represent all patients lost to follow-up. CD4 cell count outcomes were reported conditioned on continuous virological suppression. RESULTS: Seven thousand, three hundred and twenty-three treatment-naive adults (68% women) started ART between 2001 and 2007, with annual enrolment increasing from 80 in 2001 to 2087 in 2006. Of 9.8% of patients lost to follow-up for at least 6 months, 32.8% had died. Corrected mortality was 20.9% at 5 years (95% confidence interval 17.9-24.3). Mortality fell over time as patients accessed care earlier (median CD4 cell count at enrolment increased from 43 cells/microl in 2001 to 131 cells/microl in 2006). Patients who remained virologically suppressed continued to gain CD4 cells at 5 years (median 22 cells/microl per 6 months). By 5 years, 14.0% of patients had failed virologically and 12.2% had been switched to second-line therapy. CONCLUSION: At a time of considerable debate about future global funding of ART programmes in resource-poor settings, this study has demonstrated substantial and durable clinical benefits for those able to access ART throughout this period, in spite of increasing loss to follow-up.