Lynne McNamara

Early loss to follow up after enrolment in pre-ART care at a large public clinic in Johannesburg, South Africa

Objective  To estimate loss to follow up (LTFU) between initial enrolment and the first scheduled return medical visit of a pre‐antiretroviral therapy (ART) care program for patients not eligible for ART.

Lost opportunities to complete CD4+ lymphocyte testing among patients who tested positive for HIV in South Africa

OBJECTIVE To estimate rates of completion of CD4+ lymphocyte testing (CD4 testing) within 12 weeks of testing positive for human immunodeficiency virus (HIV) at a large HIV/AIDS clinic in South Africa, and to identify clinical and demographic predictors for completion. METHODS In our study, CD4 testing was considered complete once a patient had retrieved the test results. To determine the rate of CD4 testing completion, we reviewed the records of all clinic patients who tested positive for HIV between January 2008 and February 2009. We identified predictors for completion through multivariate logistic regression. FINDINGS Of the 416 patients who tested positive for HIV, 84.6% initiated CD4 testing within the study timeframe. Of these patients, 54.3% were immediately eligible for antiretroviral therapy (ART) because of a CD4 cell count ≤ 200/µl, but only 51.3% of the patients in this category completed CD4 testing within 12 weeks of HIV testing. Among those not immediately eligible for ART (CD4 cells > 200/µl), only 14.9% completed CD4 testing within 12 weeks. Overall, of HIV+ patients who initiated CD4 testing, 65% did not complete it within 12 weeks of diagnosis. The higher the baseline CD4 cell count, the lower the odds of completing CD4 testing within 12 weeks. CONCLUSION Patient losses between HIV testing, baseline CD4 cell count and the start of care and ART are high. As a result, many patients receive ART too late. Health information systems that link testing programmes with care and treatment programmes are needed.

Is there a link between African iron overload and the described mutations of the hereditary haemochromatosis gene

Over 80% of Caucasian patients with hereditary haemochromatosis are homozygotes for a C282Y mutation in the HFE gene on chromosome 6. Recent evidence suggests that a genetic factor may also be involved in the pathogenesis of African iron overload, although the locus has not been described. PCR analysis of DNA from 25 southern Africans, identified by segregation analysis as having a high probability of carrying the putative African iron‐loading gene, failed to identify any subjects with the C282Y mutation. The possible genetic defect in African iron overload appears to be different from that described in most cases of hereditary haemochromatosis in Caucasians.

Gender differences in mortality and CD4 count response among virally suppressed HIV-positive patients.

BACKGROUND Treatment outcomes for antiretroviral therapy (ART) patients may vary by gender, but estimates from current evidence may be confounded by disease stage and adherence. We investigated the gender differences in treatment response among HIV-positive patients virally suppressed within 6 months of treatment initiation. METHODS We analyzed data from 7,354 patients initiating ART between April 2004 and April 2010 at Themba Lethu Clinic, a large urban public sector treatment facility in South Africa. We estimated the relations among gender, mortality, and mean CD4 response in HIV-infected adults virally suppressed within 6 months of treatment initiation and used inverse probability of treatment weights to correct estimates for loss to follow-up. RESULTS Male patients had a 20% greater risk of death at both 24 months and 36 months of follow-up compared to females. Older patients and those with a low hemoglobin level or low body mass index (BMI) were at increased risk of mortality throughout follow-up. Men gained fewer CD4 cells after treatment initiation than did women. The mean differences in CD4 count gains made by women and men between baseline and 12, 24, and 36 months were 28.2 cells/mm(3) (95% confidence interval [CI] 22.2-34.3), 60.8 cells/mm(3) (95% CI 71.1-50.5 cells/mm(3)), and 83.0 cells/mm(3) (95% CI 97.1-68.8 cells/mm(3)), respectively. Additionally, patients with a current detectable viral load (>400 copies/mL) and older patients had a lower mean CD4 increase at the same time points. CONCLUSIONS In this initially virally suppressed population, women showed consistently better immune response to treatment than did men. Promoting earlier uptake of HIV treatment among men may improve their immunologic outcomes.

Ferroportin (Q248H) mutations in African families with dietary iron overload

Background:  Dietary iron overload found in sub‐Saharan Africa might be caused by an interaction between dietary iron and an iron‐loading gene. Caucasian people with ferroportin gene mutations have iron overload histologically similar to that found in African patients with iron overload. Ferroportin is also implicated in the hypoferremic response to inflammation. The prevalence of the ferroportin Q248H mutation, unique to African people, and its association with dietary iron overload, mean cell volume (MCV) and C‐reactive protein (CRP) were examined in 19 southern African families.

Non-transferrin-bound iron and hepatic dysfunction in African dietary iron overload.

Background: Circulating iron is normally bound to transferrin. Non‐transferrin‐bound iron (NTBI) has been described in most forms of iron overload, but has not been studied in African dietary iron overload. This abnormal iron fraction is probably toxic, but this has not been demonstrated.

HIV–HBV coinfection among South African patients receiving antiretroviral therapy

There are approximately 33 million individuals with HIV infection worldwide. The majority of infections are in southern Africa where hepatitis B is also known to be endemic. As access to life-saving antiretroviral therapy (ART) increases, the possibility for hepatitis B treatment resistance increases because most ART regimens contain lamivudine. Patients coinfected with HBV are therefore receiving monotherapy for HBV infection, leading to possible HBV-resistant mutants and the concurrent public health effect thereof. Additional information is needed on the prevalence of HIV-HBV coinfection and treatment response to ART. We present a summary of the information available from South Africa to date.

CD4 criteria improves the sensitivity of a clinical algorithm developed to identify viral failure in HIV-positive patients on antiretroviral therapy

Several studies from resource‐limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers.

Antiretroviral Therapy Initiation during Tuberculosis Treatment and HIV-RNA and CD4-T Lymphocyte Responses

SETTING A large human immunodeficiency virus (HIV) clinic in South Africa. OBJECTIVE To examine the effect of initiating antiretroviral therapy (ART) on CD4 and viral response at different time periods during anti-tuberculosis treatment (<14 days, 15-60 days, or ≥60 days) using prospectively collected clinical data. METHODS Cohort data analysis for 1499 patients with tuberculosis (TB) and HIV co-infection classified according to timing of ART after the initiation of anti-tuberculosis treatment. RESULTS In adjusted modified Poisson regression models, CD4 and viral responses showed no significant differences according to timing of ART initiation (failure to increase CD4 by 6 months, <14 days vs. >60 days: RR 1.02, 95%CI 0.85-1.22; 15-60 days vs. >60 days: RR 1.00, 95%CI 0.86-1.15; failure to suppress virus by 6 months, <14 days vs. >60 days: RR 0.98, 95%CI 0.59-1.63; 15-60 days vs. >60 days: RR 0.96, 95%CI 0.66-1.41 and viral rebound at 12 months, 14 days vs. >60 days: RR 1.43, 95%CI 0.50-4.12; 15-60 days vs. >60 days: RR 1.14, 95%CI 0.39-3.34). Similar estimates were found in analysis restricted to patients with severe immunosuppression. CONCLUSION Concerns over the overlapping impact of anti-tuberculosis treatment with ART on ART response should not be a reason for delaying ART in patients with HIV-associated TB.

Design and methodology of a study on colorectal cancer in Johannesburg, South Africa: Design and methodology of a study on colorectal cancer

Cancer is one of the foremost causes of morbidity and mortality worldwide. Globally, colorectal cancer (CRC) is the third most diagnosed and fourth most important cause of cancer death. A total of 70% of all CRC‐related deaths occur in low‐ and middle‐income countries. In Sub‐Saharan Africa (SSA), estimating the burden of CRC is difficult. Only 27 of 43 SSA countries have formalized cancer registration systems; data quality is variable and national coverage rare.