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1.  Breast cancer characteristics and HIV among 1,092 women in Soweto, South Africa 
In the low-income HIV-endemic regions of sub-Saharan Africa, malignancies related to HIV have long been recognized as a major public health problem. However, epithelial malignancies associated with older age, such as breast cancer, are also rising dramatically in those regions. We compared consecutive HIV-positive and -negative black women diagnosed with breast cancer at a large public hospital in Soweto, South Africa, on age, year of diagnosis, stage, grade, and receptor status, and grouped HIV-positive patients by CD4 cell counts. We computed prevalence ratios of the associations of HIV status and CD4 category with stage, grade, receptor status, and among the HIV-positive patients, receipt of ART, controlling for age and year of diagnosis. Of 1,092 patients, 765 were tested for HIV; 151 (19.7 %) tested positive, a prevalence similar to that in the source population. Although, HIV-positive patients were younger than HIV-negative patients (p < 0.001), HIV status was not associated with the tumor characteristics. Thirty-seven women (25.9 %) had CD4 cell counts <200 cells/μl. Patients in that severely immunocompromised group were older than those in the other groups (p = 0.01). This study is the first to analyze the association of HIV with breast cancer in a large sample. Based on similar HIV prevalence in our sample and the population of the hospital’s catchment area, clinicians serving HIV-endemic communities should promote routine HIV testing of younger breast cancer patients and immediate treatment of those who test positive, prior to the initiation of chemotherapy. Research is needed on treatment and outcomes given HIV and low CD4 cell count.
PMCID: PMC3706733  PMID: 23801159
Breast cancer and HIV; South Africa; Breast cancer and race/ethnicity; HIV and cancer
2.  Antiretroviral Outcomes in South African Prisoners: A Retrospective Cohort Analysis 
PLoS ONE  2012;7(3):e33309.
Background and Methods
Little is known about antiretroviral therapy (ART) outcomes in prisoners in Africa. We conducted a retrospective review of outcomes of a large cohort of prisoners referred to a public sector, urban HIV clinic. The review included baseline characteristics, sequential CD4 cell counts and viral load results, complications and co-morbidities, mortality and loss to follow-up up to 96 weeks on ART.
148 inmates (133 male) initiated on ART were included in the study. By week 96 on ART, 73% of all inmates enrolled in the study and 92% of those still accessing care had an undetectable viral load (<400copies/ml). The median CD4 cell count increased from 122 cells/mm3 at baseline to 356 cells/mm3 by 96 weeks. By study end, 96 (65%) inmates had ever received tuberculosis (TB) therapy with 63 (43%) receiving therapy during the study: 28% had a history of TB prior to ART initiation, 33% were on TB therapy at ART initiation and 22% developed TB whilst on ART. Nine (6%) inmates died, 7 in the second year on ART. Loss to follow-up (LTF) was common: 14 (9%) patients were LTF whilst still incarcerated, 11 (7%) were LTF post-release and 9 (6%) whose movements could not be traced. 16 (11%) inmates had inter-correctional facility transfers and 34 (23%) were released of whom only 23 (68%) returned to the ART clinic for ongoing follow-up.
Inmates responded well to ART, despite a high frequency of TB/HIV co-infection. Attention should be directed towards ensuring eligible prisoners access ART programs promptly and that inter-facility transfers and release procedures facilitate continuity of care. Institutional TB control measures should remain a priority.
PMCID: PMC3310000  PMID: 22470448
3.  Contrasting Reasons for Discontinuation of Antiretroviral Therapy in Workplace and Public-Sector HIV Programs in South Africa 
AIDS Patient Care and STDs  2011;25(1):53-59.
We investigated reasons for clinical follow-up and treatment discontinuation among HIV-infected individuals receiving antiretroviral therapy (ART) in a public-sector clinic and in a workplace clinic in South Africa. Participants in a larger cohort study who had discontinued clinical care by the seventh month of treatment were traced using previously provided locator information. Those located were administered a semistructured questionnaire regarding reasons for discontinuing clinical follow-up. Participants who had discontinued antiretroviral therapy were invited to participate in further in-depth qualitative interviews. Fifty-one of 144 (35.4%) in the workplace cohort had discontinued clinical follow-up by the seventh month of treatment. The median age of those who discontinued follow-up was 46 years and median educational level was five years. By contrast, only 16.5% (44/267) of the public-sector cohort had discontinued follow-up. Among them the median age was 37.5 years and median education was 11 years. Qualitative interviews were conducted with 17 workplace participants and 10 public-sector participants. The main reasons for attrition in the workplace were uncertainty about own HIV status and above the value of ART, poor patient–provider relationships and workplace discrimination. In the public sector, these were moving away and having no money for clinic transport. In the workplace, efforts to minimize the time between testing and treatment initiation should be balanced with the need to provide adequate baseline counseling taking into account existing concepts about HIV and ART. In the public sector, earlier diagnosis and ART initiation may help to reduce early mortality, while links to government grants may reduce attrition.
PMCID: PMC3030909  PMID: 21214378
4.  Persistent High Burden of Invasive Pneumococcal Disease in South African HIV-Infected Adults in the Era of an Antiretroviral Treatment Program 
PLoS ONE  2011;6(11):e27929.
Highly active antiretroviral treatment (HAART) programs have been associated with declines in the burden of invasive pneumococcal disease (IPD) in industrialized countries. The aim of this study was to evaluate trends in IPD hospitalizations in HIV-infected adults in Soweto, South Africa, associated with up-scaling of the HAART program from 2003 to 2008.
Laboratory-confirmed IPD cases were identified from 2003 through 2008 through an existing surveillance program. The period 2003-04 was designated as the early-HAART era, 2005–06 as the intermediate-HAART era and 2007–08 as the established-HAART era. The incidence of IPD was compared between the early-HAART and established-HAART eras in HIV-infected and–uninfected individuals.
A total of 2,567 IPD cases among individuals older than 18 years were reported from 2003 through 2008. Overall incidence of IPD (per 100,000) did not change during the study period in HIV-infected adults (207.4 cases in the early-HAART and 214.0 cases in the established-HAART era; p = 0.55). IPD incidence, actually increased 1.16-fold (95% CI: 1.01; 1.62) in HIV-infected females between the early-and established-HAART eras (212.1 cases and 246.2 cases, respectively; p = 0.03). The incidence of IPD remained unchanged in HIV-uninfected adults across the three time periods.
Despite a stable prevalence of HIV and the increased roll-out of HAART for treatment of AIDS patients in our setting, the burden of IPD has not decreased among HIV-infected adults. The study indicates a need for ongoing monitoring of disease and HAART program effectiveness to reduce opportunistic infections in African adults with HIV/AIDS, as well as the need to consider alternate strategies including pneumococcal conjugate vaccine immunization for the prevention of IPD in HIV-infected adults.
PMCID: PMC3225377  PMID: 22140487
5.  A study of patient attitudes towards decentralisation of HIV care in an urban clinic in South Africa 
In South Africa, limited human resources are a major constraint to achieving universal antiretroviral therapy (ART) coverage. Many of the public-sector HIV clinics operating within tertiary facilities, that were the first to provide ART in the country, have reached maximum patient capacity. Decentralization or "down-referral" (wherein ART patients deemed stable on therapy are referred to their closest Primary Health Clinics (PHCs) for treatment follow-up) is being used as a possible alternative of ART delivery care. This cross-sectional qualitative study investigates attitudes towards down-referral of ART delivery care among patients currently receiving care in a centralized tertiary HIV clinic.
Ten focus group discussions (FGDs) with 76 participants were conducted in early 2008 amongst ART patients initiated and receiving care for more than 3 months in the tertiary HIV clinic study site. Eligible individuals were invited to participate in FGDs involving 6-9 participants, and lasting approximately 1-2 hours. A trained moderator used a discussion topic guide to investigate the main issues of interest including: advantages and disadvantages of down-referral, potential motivating factors and challenges of down-referral, assistance needs from the transferring clinic as well as from PHCs.
Advantages include closeness to patients' homes, transport and time savings. However, patients favour a centralized service for the following reasons: less stigma, patients established relationship with the centralized clinic, and availability of ancillary services. Most FGDs felt that for down-referral to occur there needed to be training of nurses in patient-provider communication.
Despite acknowledging the down-referral advantages of close proximity and lower transport costs, many participants expressed concerns about lack of trained HIV clinical staff, negative patient interactions with nurses, limited confidentiality and stigma. There was consensus that training of nurses and improved health systems at the local clinics were needed if successful down-referral was to take place.
PMCID: PMC3167749  PMID: 21871068
decentralization; down-referral; South Africa; ART; level of care
6.  nViremia and drug resistance among HIV-1 patients on antiretroviral treatment – a cross-sectional study in Soweto, South Africa 
AIDS (London, England)  2010;24(11):1679-1687.
We assessed risk factors for viremia and drug resistance (DR) among long-term recipients of antiretroviral therapy (ART) in South Africa.
In 2008, we conducted a cross-sectional study among patients receiving ART for ≥12 months. Genotypic resistance testing was performed on individuals with a viral load >400 RNA copies/ml. Multiple logistic regression analysis was used to assess associations.
Of 998 subjects, 75% were women with a median age of 41. Most (64%) had been on treatment for >3 years. The prevalence of viremia was 14% (n=139); 12% (102/883) on first-line (i.e. NNRTI based regimen) and 33% (37/115) on second-line (i.e. PI based regimen) ART. Of viremic patients, 78% had DR mutations. For NRTIs, NNRTIs and PIs the prevalence of mutations was 64%, 81% and 2% among first-line and 29%, 54% and 6% among second-line failures respectively. M184V/I, K103N and V106A/M were the most common mutations.
Significant risk factors associated with viremia on first-line included concurrent tuberculosis treatment (OR 6.4, 2.2-18.8, p<0.01) and a recent history of poor adherence (OR 2.7, 1.3-5.6, p=0.01). Among second-line failures, attending a public clinic (OR 4.6, 1.8-11.3, p<0.01) and not having a refrigerator at home (OR 6.7, 1.2-37.5, p=0.03) were risk factors for virological failure.
Risk factors for viral failure were line-regimen dependent. Second-line ART recipients had a higher rate of viremia, albeit with infrequent PI DR mutations. Measures to maintain effective virologic suppression should include increased adherence counseling, attention to concomitant tuberculosis treatment and heat-stable formulations of second-line ART regimens.
PMCID: PMC2894994  PMID: 20453629
Antiretroviral therapy; HIV; adherence; HIV drug resistance; South Africa; Viral failure
7.  Contrasting predictors of poor antiretroviral therapy outcomes in two South African HIV programmes: a cohort study 
BMC Public Health  2010;10:430.
Many national antiretroviral therapy (ART) programmes encourage providers to identify and address baseline factors associated with poor treatment outcomes, including modifiable adherence-related behaviours, before initiating ART. However, evidence on such predictors is scarce, and providers judgement may often be inaccurate. To help address this evidence gap, this observational cohort study examined baseline factors potentially predictive of poor treatment outcomes in two ART programmes in South Africa, with a particular focus on determinants of adherence.
Treatment-naïve patients starting ART were enrolled from a community and a workplace ART programme. Potential baseline predictors associated with poor treatment outcomes (defined as viral load > 400 copies/ml or having discontinued treatment by six months) were assessed using logistic regression. Exposure variables were organised for regression analysis using a hierarchical framework.
38/227 (17%) of participants in the community had poor treatment outcomes compared to 47/117 (40%) in the workplace. In the community, predictors of worse outcomes included: drinking more than 20 units of alcohol per week, having no prior experience of chronic medications, and consulting a traditional healer in the past year (adjusted odds ratio [aOR] 15.36, 95% CI 3.22-73.27; aOR 2.30, 95%CI 1.00-5.30; aOR 2.27, 95% CI 1.00-5.19 respectively). Being male and knowing someone on ART were associated with better outcomes (aOR 0.25, 95%CI 0.09-0.74; aOR 0.44, 95%CI 0.19-1.01 respectively). In the workplace, predictors of poor treatment outcomes included being uncertain about the health effects of ART and a traditional healer's ability to treat HIV (aOR 7.53, 95%CI 2.02-27.98; aOR 4.40, 95%CI 1.41-13.75 respectively). Longer pre-ART waiting time (2-12 weeks compared to <2 weeks) predicted better treatment outcomes (aOR 0.13, 95% CI 0.03-0.56).
Baseline predictors of poor treatment outcomes were largely unique to each programme, likely reflecting different populations and pathways to HIV care. In the workplace, active promotion of HIV testing may have extended ART to individuals who, without provider initiation, would not have spontaneously sought care. As provider-initiated testing makes ART available to individuals less motivated to seek care, patients may need additional adherence support, especially addressing uncertainty about the health benefits of ART.
PMCID: PMC2920888  PMID: 20649946

Results 1-7 (7)