Brief Report: Improving Early Infant Diagnosis Observations: Estimates of Timely HIV Testing and Mortality Among HIV-Exposed Infants.

BACKGROUND: Improving efforts toward elimination of mother-to-child transmission of HIV requires timely early infant diagnosis (EID) among all HIV-exposed infants, but the occurrence of timely EID and infant survival may be underascertained in routine, facility-bound program data. METHODS: From March 2015 to May 2015, we traced a random sample of HIV-positive mother and HIV-exposed infant pairs lost to follow-up for EID in facility registers in Zimbabwe. We incorporated updated information into weighted survival analyses to estimate incidence of EID and death. Reasons for no EID were surveyed from caregivers. RESULTS: Among 2651 HIV-positive women attending antenatal care, 1823 (68.8%) infants had no documented EID by 3 months of age. Among a random sample of 643 (35.3%) HIV-exposed infants lost to follow-up for EID, vital status was ascertained among 371 (57.7%) and updated care status obtained from 256 (39.8%) mothers traced. Among all HIV-infected mother-HIV-exposed infant pairs, weighted estimates found cumulative incidence of infant death by 90 days of 3.9% (95% confidence interval: 3.4% to 4.4%). Cumulative incidence of timely EID with death as a competing risk was 60%. The most frequently cited reasons for failure to uptake EID were "my child died" and "I didn't know I should have my child tested." CONCLUSIONS: Our findings indicate uptake of timely EID among HIV-exposed infants is underestimated in routine health information systems. High, early mortality among HIV-exposed infants underscores the need to more effectively identify HIV-positive mother-HIV exposed infant pairs at high risk of adverse outcomes and loss to follow-up for enhanced interventions.

Lessons learned: Retrospective assessment of outcomes and management of patients with advanced HIV disease in a semi-urban polyclinic in Epworth, Zimbabwe.

INTRODUCTION: HIV continues to be one of the leading causes of infectious death worldwide and presentation with advanced HIV disease is associated with increased morbidity and mortality. Recommendations for the management of advanced HIV disease include prompt screening and treatment of opportunistic infections, rapid initiation of ART and intensified adherence support. We present treatment outcomes of a cohort of patients presenting with advanced HIV disease in a semi-urban Zimbabwean polyclinic. METHODS: Retrospective cohort analysis of adult patients enrolled for care at Epworth polyclinic, Zimbabwe between 2007 and end June 2016. Treatment outcomes at 6 and 12 months were recorded. Multivariate logistical regression analysis was undertaken to identify risk factors for presentation with advanced HIV Disease (CD4 count less than 200 cells/mm3 or WHO stage 3 or 4) and risks for attrition at 12 months. RESULTS: 16,007 anti-retroviral therapy naive adult patients were included in the final analysis, 47.4% of whom presented with advanced HIV disease. Patients presenting with advanced HIV disease had a higher mortality rate at 12 months following enrollment compared to early stage patients (5.11% vs 0.45%). Introduction of a package of differentiated care for patients with a CD4 count of less than 100 cells/mm3 resulted in diagnosis of cryptococcal antigenaemia in 7% of patients and a significant increase in the diagnosis of TB, although there was no significant difference in attrition at 6 or 12 months for these patients compared to those enrolled prior to the introduction of the differentiated care. CONCLUSIONS: The burden of advanced HIV disease remained high over the study period in this semi-urban polyclinic in Zimbabwe. Introduction of a package of differentiated care for those with advanced HIV disease increased the diagnosis of opportunistic infections and represents a model of care which can be replicated in other polyclinics in the resource constrained Zimbabwean context.

Impact of Point-of-Care CD4 Testing on Retention in Care Among HIV-Positive Pregnant and Breastfeeding Women in the Context of Option B+ in Zimbabwe: A Cluster Randomized Controlled Trial.

INTRODUCTION: Scale-up of Option B+ in Zimbabwe has increased antiretroviral therapy (ART) coverage but patient loss-to-follow-up remains high; thus, effective strategies to improve retention in care are needed. Evidence for Elimination, a cluster randomized controlled trial, evaluated the impact of point-of-care (POC) CD4 testing with CD4 count-specific adherence counseling on rates of retention among 1150 HIV-positive pregnant women initiating ART in Zimbabwe. METHODS: Thirty-two primary care health facilities were randomized to offer either standard-of-care (SOC) or POC CD4 testing plus CD4-specific counseling to clients (POC Plus). The primary outcome was the proportion of HIV-positive pregnant women retained on ART after 12 months, calculated by cluster-adjusted proportions, unadjusted and adjusted relative risks (RR and aRR, respectively). RESULTS: Retention in care 12 months after initiation was 50.7% and 54.5% in the POC Plus and SOC arms, respectively (RR 0.93, 95% confidence interval [CI]: 0.78 to 1.11; aRR 0.91, 95% CI: 0.77 to 1.07). Although considered not retained, 9.7% transferred to another facility and 0.2% died. Most women, 95.3% in POC Plus and 92.9% in SOC, initiated ART within 1 month of antenatal booking (RR 1.03, 95% CI: 0.97 to 1.08). DISCUSSION: Although patient retention was similar in both arms, women in the POC Plus arm were more likely to have received a CD4 test at booking and a repeat CD4 test later in care. CD4 is no longer required for treatment initiation but is still recommended in national guidelines and is of value in clinical management. Further work is needed to identify effective strategies to increase patient retention in ART care.

Does provision of point-of-care CD4 technology and early knowledge of CD4 levels affect early initiation and retention on antiretroviral treatment in HIV-positive pregnant women in the context of Option B+ for PMTCT?

Evidence for Elimination (E4E) is a collaborative project established in 2012 as part of the INSPIRE (INtegrating and Scaling up PMTCT through Implementation REsearch) initiative. E4E is a cluster-randomized trial with 2 arms; Standard of care and "POC Plus" [in which point-of-care (POC) CD4 devices and related counseling support are provided]; aimed at improving retention-in-care of HIV-infected pregnant women and mothers. In November 2013, Zimbabwe adopted Option B+ for HIV-positive pregnant women under which antiretroviral treatment eligibility is no longer based on CD4 count. However, Ministry of Health and Child Care guidelines still require baseline and 6-monthly CD4 testing for treatment monitoring, until viral load testing becomes widely available. Considering the current limited capacity for viral-load testing, the significant investments in CD4 testing already made and the historical reliance on CD4 by health care workers for determining eligibility for antiretroviral treatment, E4E seeks to compare the impact of the provision of POC CD4 technology and early knowledge of CD4 levels on retention-in-care at 12 months, with the current standard of routine, laboratory-based CD4 testing. The study also compares rates of initiation and time-to-initiation between the 2 arms and according to level of maternal CD4 count, the cost of retaining HIV-positive pregnant women in care and the acceptability and feasibility of POC CD4 in the context of Option B+. Outcome measures are derived from routine health systems data. E4E will provide data on POC CD4 testing and retention-in-care associated with Option B+ and serve as an early learning platform to inform implementation of Option B+ in Zimbabwe.

High-dose rifapentine with moxifloxacin for pulmonary tuberculosis.

BACKGROUND: Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed. METHODS: We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals. RESULTS: We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, -1.8 percentage points; 90% confidence interval [CI], -6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, -4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4). CONCLUSIONS: The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.).

Determinants of perinatal mortality in Marondera district, Mashonaland East Province of Zimbabwe, 2009: a case control study.

BACKGROUND: Marondera District recorded perinatal mortality ratios of 58.6/1000 and 64.6/1000 live births in 2007 and 2008 respectively. These ratios were above provincial averages of 32/1000 and 36/1000 during the same periods. We determined factors associated with perinatal mortality in Marondera District. METHODS: A 1:2 unmatched case control study was carried out from June to August 2009. A case was any mother in Marondera District who had a stillbirth or early neonatal death from 01/08/2008 to 31/07/2009. A control was any mother whose baby survived the perinatal period during the same period. We calculated Odds Ratios and their 95% confidence intervals. RESULTS: We interviewed 103 cases and 206 controls. Primary or no maternal education [OR=5.50 (3.14-9.33)] labor complications [OR=7.56 (4.38-13.06)], home delivery [OR=7.38 (4.03-13.68)] and preterm delivery [OR=15.06 (8.24-27.54)] increased the risk for perinatal mortality. Antenatal care booking [OR=0.19 (0.10-0.34)], having a gainfully employed husband [OR=0.36 (0.20-0.63)] and living within 5 km of a health facility [OR=0.41 (0.22-0.78)] reduced the risk. Independent determinants of perinatal mortality included being apostolic [AOR=3.11 (1.05-9.18)], having a home delivery [AOR 7.17 (2.48-20.73)], experiencing labor complications [AOR=8.99 (3.11-25.98)], maternal HIV infection [AOR=5.36 (2.02-14.26)], antenatal care booking [AOR=0.32 (0.18-0.87)] and birth weight below 2500 g [AOR=9.46 (3.91-27.65)]. CONCLUSION: Labor complications, belonging to apostolic sect, having a home delivery, maternal HIV infection, low birth weight and antenatal care booking were independently associated with perinatal mortality. Health worker training in emergency management of obstetric and neonatal care was initiated. Marondera District started holding perinatal mortality meetings.