In 2010, there were approximately 8.8 million incident cases of tuberculosis (TB) worldwide. The treatment of TB is at least six months long and may be complicated by a high pill burden. In addition, TB patients often do not take their medication on schedule simply because they forget. Mobile phone text messaging has the potential to help promote TB treatment adherence. We, therefore, propose to conduct a review of current best evidence for the use of mobile phone text messaging to promote patient adherence to TB treatment.
This is a systematic review of the literature. We will preferably include randomized controlled trials (RCTs). However, non-randomized studies (NRS) will be considered if there is an inadequate number of RCTs.
We will search PubMed, EMBASE, CINAHL, CENTRAL, Science Citation Index, Africa-Wide Information, and WHOLIS electronic databases for eligible studies available by 30 November 2012 regardless of language or publication status. We will also check reference lists for additional studies, identify abstracts from conference proceedings and communicate with authors for any relevant material.
At least two authors will independently screen search outputs, select studies, extract data and assess the risk of bias (using separate criteria for RCTs and NRS); resolving discrepancies by discussion and consensus. We will assess clinical heterogeneity by examining the types of participants, interventions and outcomes in each study and pool studies judged to be clinically homogenous. We will also assess statistical heterogeneity using the chi-square test of homogeneity and quantify it using the I-square statistic. If study results are found to be statistically homogeneous (that is heterogeneity P > 0.1), we will pool them using the fixed-effect meta-analysis. Otherwise, we will use random-effects meta-analysis. We will calculate risk ratios and their corresponding 95% confidence intervals for dichotomous outcomes, and mean differences for continuous outcomes. For other outcomes without quantitative data, a descriptive analysis will be used.
Our results can be used by researchers and policy-makers to help inform them of the efficacy of mobile phone text messaging interventions to promote patient adherence to TB treatment.
Mobile phone; Text messages; Tuberculosis treatment; Anti-tubercular agents; Adherence; Compliance
Antiretroviral therapy (ART) initiation in eligible HIV-infected pregnant women is an important intervention to promote maternal and child health. Increasing the duration of ART received before delivery plays a major role in preventing vertical HIV transmission, but pregnant women across Africa experience significant delays in starting ART, partly due the perceived need to deliver ART counseling and patient education before ART initiation. We examined whether delaying ART to provide pre-ART counseling was associated with improved outcomes among HIV-infected women in Cape Town, South Africa.
We undertook a retrospective cohort study of 490 HIV-infected pregnant women referred to initiate treatment at an urban ART clinic. At this clinic all patients including pregnant women are screened by a clinician and then undergo three sessions of counseling and patient education prior to starting treatment, commonly introducing delays of 2–4 weeks before ART initiation. Data on viral suppression and retention in care after ART initiation were taken from routine clinic records.
A total of 382 women initiated ART before delivery (78%); ART initiation before delivery was associated with earlier gestational age at presentation to the ART service (p < 0.001). The median delay between screening and ART initiation was 21 days (IQR, 14–29 days). Overall, 84.7%, 79.6% and 75.0% of women who were pregnant at the time of ART initiation were retained in care at 4, 8 and 12 months after ART initiation, respectively. Among those retained, 91% were virally suppressed at each follow-up visit. However the delay from screening to ART initiation was not associated with retention in care and/or viral suppression throughout the first year on ART in unadjusted or adjusted analyses.
A substantial proportion of eligible pregnant women referred for ART do not begin treatment before delivery in this setting. Among women who do initiate ART, delaying initiation for patient preparation is not associated with improved maternal outcomes. Given the need to maximize the duration of ART before delivery for prevention of mother-to-child HIV transmission, there is an urgent need for new strategies to help expedite ART initiation in eligible pregnant women.
Antiretroviral therapy; Pregnancy; Patient preparation; Prevention of mother-to-child transmission (PMTCT); HIV/AIDS; South Africa
Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection.
LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay.
32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and < 50 cells/μl, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls.
Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.
The HIV epidemic in Sub Saharan Africa has been traditionally assumed to be driven by high risk heterosexual and vertical transmission. However, there is an increasing body of data highlighting the disproportionate burden of HIV infection among MSM in the generalized HIV epidemics across of Southern Africa. In South Africa specifically, there has been an increase in attention focused on the risk status and preventive needs of MSM both in urban centers and peri-urban townships. The study presented here represents the first evaluation of HIV prevalence and associations of HIV infection among MSM in the peri-urban townships of Cape Town.
The study consisted of an anonymous probe of 200 men, reporting ever having had sex with another man, recruited through venue-base sampling from January to February, 2009.
Overall, HIV prevalence was 25.5% (n = 51/200). Of these prevalent HIV infections, only 6% of HIV-1 infected MSM were aware of their HIV status (3/50). 0% of men reported always having safe sex as defined by always wearing condoms during sex and using water-based lubricants. Independent associations with HIV infection included inconsistent condom use with male partners (aOR 2.3, 95% CI 1.0-5.4), having been blackmailed (aOR 4.4, 95% CI 1.6-20.2), age over 26 years (aOR 4.2, 95% CI 1.6-10.6), being unemployed (aOR 3.7, 95% CI 1.5-9.3), and rural origin (aOR 6.0, 95% CI 2.2-16.7). Bisexual activity was reported by 17.1% (34/199), and a total of 8% (16/200) reported having a regular female partner. Human rights violations were common with 10.5% (n = 21/200) reporting having been blackmailed and 21.0% (n = 42/200) reporting being afraid to seek health care.
The conclusions from this study include that a there is a high risk and underserved population of MSM in the townships surrounding Cape Town. The high HIV prevalence and high risk sexual practices suggest that prevalence will continue to increase among these men in the context of an otherwise slowing epidemic. These data further highlight the need to better characterize risk factors for HIV prevention and appropriate targeted combination packages of HIV interventions including biomedical, behavioural, and structural approaches to mitigate HIV risk among these men.
Understanding of the transmission dynamics of tuberculosis (TB) in high TB and HIV prevalent settings is required in order to develop effective intervention strategies for TB control. However, there are little data assessing incidence of TB infection in adolescents in these settings.
We performed a tuberculin skin test (TST) and HIV survey among secondary school learners in a high HIV and TB prevalence community. TST responses to purified protein derivative RT23 were read after 3 days. HIV-infection was assessed using Orasure® collection device and ELISA testing. The results of the HIV-uninfected participants were combined with those from previous surveys among primary school learners in the same community, and force of TB infection was calculated by age.
The age of 820 secondary school participants ranged from 13 to 22 years. 159 participants had participated in the primary school surveys. At a 10 mm cut-off, prevalence of TB infection among HIV-uninfected and first time participants, was 54% (n = 334/620). HIV prevalence was 5% (n = 40/816). HIV infection was not significantly associated with TST positivity (p = 0.07). In the combined survey dataset, TB prevalence was 45% (n = 645/1451), and was associated with increasing age and male gender. Force of infection increased with age, from 3% to 7.3% in adolescents ≥20 years of age.
We show a high force of infection among adolescents, positively associated with increasing age. We postulate this is due to increased social contact with infectious TB cases. Control of the TB epidemic in this setting will require reducing the force of infection.
The progression of human tuberculosis to active disease and transmission involves the development of a caseous granuloma that cavitates and releases infectious Mycobacterium tuberculosis bacilli. In the current study, we exploited genome-wide microarray analysis to determine that genes for lipid sequestration and metabolism were highly expressed in caseous tuberculosis granulomas. Immunohistological analysis of these granulomas confirmed the disproportionate abundance of the proteins involved in lipid metabolism in cells surrounding the caseum; namely, adipophilin, acyl-CoA synthetase long-chain family member 1, and saposin C. Biochemical analysis of the lipid species within the caseum identified cholesterol, cholesteryl esters, triacylglycerols, and lactosylceramide, which implicated low-density lipoprotein-derived lipids as the most likely source. M. tuberculosis infection in vitro induced lipid droplet formation in murine and human macrophages. Furthermore, the M. tuberculosis cell wall lipid, trehalose dimycolate, induced a strong granulomatous response in mice, which was accompanied by foam cell formation. These results provide molecular and biochemical evidence that the development of the human tuberculosis granuloma to caseation correlates with pathogen-mediated dysregulation of host lipid metabolism.
High rates of loss to follow-up (LTFU) are undermining rapidly expanding antiretroviral treatment (ART) services in sub-Saharan Africa. The intelligent dispensing of ART (iDART) is an open-source electronic pharmacy system that provides an efficient means of generating lists of patients who have failed to pick-up medication. We determined the duration of pharmacy delay that optimally identified true LTFU.
We conducted a retrospective cross-sectional study of a community-based ART cohort in Cape Town, South Africa. We used iDART to identify groups of patients known to be still enrolled in the cohort on the 1st of April 2008 that had failed to pick-up medication for periods of ≥ 6, ≥ 12, ≥ 18 and ≥ 24 weeks. We defined true LTFU as confirmed failure to pick up medication for 3 months since last attendance. We then assessed short-term and long-term outcomes using a prospectively maintained database and patient records.
On the date of the survey, 2548 patients were registered as receiving ART but of these 85 patients (3.3%) were found to be true LTFU. The numbers of individuals (proportion of the cohort) identified by iDART as having failed to collect medication for periods of ≥6, ≥12, ≥18 and ≥24 weeks were 560 (22%), 194 (8%), 117 (5%) and 80 (3%), respectively. The sensitivities of these pharmacy delays for detecting true LTFU were 100%, 100%, 62.4% and 47.1%, respectively. The corresponding specificities were 80.7%, 95.6%, 97.4% and 98.4%. Thus, the optimal delay was ≥12 weeks since last attendance at this clinic (equivalent to 8 weeks since medication ran out). Pharmacy delays were also found to be significantly associated with LTFU and death one year later.
The iDART electronic pharmacy system can be used to detect patients potentially LTFU and who require recall. Using a short a cut-off period was too non-specific for LTFU and would require the tracing of very large numbers of patients. Conversely prolonged delays were too insensitive. Of the periods assessed, a ≥12 weeks delay appeared optimal. This system requires prospective evaluation to further refine its utility.
Interferon-gamma (IFN-γ) ELISPOT assays incorporating Mycobacterium tuberculosis-specific antigens are useful in the diagnosis of tuberculosis (TB) or latent infection. However, their utility in patients with advanced HIV is unknown. We studied determinants of ELISPOT responses among patients with advanced HIV infection (but without active TB) living in a South African community with very high TB notification rates.
IFN-γ responses to ESAT-6 and CFP-10 in overnight ELISPOT assays and in 7-day whole blood assays (WBA) were compared in HIV-infected patients (HIV+, n = 40) and healthy HIV-negative controls (HIV-, n = 30) without active TB. Tuberculin skin tests (TSTs) were also done.
ELISPOTs, WBAs and TSTs were each positive in >70% of HIV- controls, reflecting very high community exposure to M. tuberculosis. Among HIV+ patients, quantitative WBA responses and TSTs (but not the proportion of positive ELISPOT responses) were significantly impaired in those with CD4 cell counts <100 cells/μl compared to those with higher counts. In contrast, ELISPOT responses (but not WBA or TST) were strongly related to history of TB treatment; a much lower proportion of HIV+ patients who had recently completed treatment for TB (n = 19) had positive responses compared to those who had not been treated (11% versus 62%, respectively; P < 0.001). Multivariate analysis confirmed that ELISPOT responses had a strong inverse association with a history of recent TB treatment (adjusted OR = 0.06, 95%CI = 0.10–0.40, P < 0.01) and that they were independent of CD4 cell count and viral load. Among HIV+ individuals who had not received TB treatment both the magnitude and proportion of positive ELISPOT responses (but not TST or WBA) were similar to those of HIV-negative controls.
The proportion of positive ELISPOT responses in patients with advanced HIV infection was independent of CD4 cell count but had a strong inverse association with history of TB treatment. This concurs with the previously documented low TB risk among patients in this cohort with a history of recent treatment for TB. These data suggest ELISPOT assays may be useful for patient assessment and as an immuno-epidemiological research tool among patients with advanced HIV and warrant larger scale prospective evaluation.
Patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency. Previous data suggest that such patients may have diminished capacity for CD4 cell count recovery.
Rates of CD4 cell increase were determined over 48 weeks among ART-naïve individuals (n = 596) commencing ART in a South African community-based ART programme.
The CD4 cell count increased from a median of 97 cells/μl at baseline to 261 cells/μl at 48 weeks and the proportion of patients with a CD4 cell count <100 cells/μl decreased from 51% at baseline to just 4% at 48 weeks. A rapid first phase of recovery (0–16 weeks, median rate = 25.5 cells/μl/month) was followed by a slower second phase (16–48 weeks, median rate = 7.7 cells/μl/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts <50 cells/μl had similar rates of phase 1 CD4 cell recovery (P = 0.42), greater rates of phase 2 recovery (P = 0.007) and a lower risk of immunological non-response (P = 0.016). Among those that achieved a CD4 cell count >500 cells/μl at 48 weeks, 19% had baseline CD4 cell counts <50 cells/μl. However, the proportion of these patients that attained a CD4 count 200 cells/μl at 48 weeks was lower than those with higher baseline CD4 cell counts.
Patients in this cohort with baseline CD4 cell counts <50 cells/μl have equivalent or greater capacity for immunological recovery during 48 weeks of ART compared to those with higher baseline CD4 cell counts. However, their CD4 counts remain <200 cells/μl for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.
Tuberculosis (TB) is a serious public health problem in many parts of the world. Strategies to curb the spread of TB must match the multifaceted nature of the epidemic. The use of mass media is one of the important strategies in communicating behavioural change in relation to TB prevention and the treatment. However, the benefits of this intervention are unclear. We, therefore, plan to conduct a systematic review on the effects of mass media interventions on TB awareness, health-seeking behaviour and health service utilisation.
Methods and analysis
We will preferably include randomised controlled trials (RCTs) in this systematic review. However, non-randomised studies will be included if there is an inadequate number of RCTs. We will perform electronic searches in PubMed, Scopus and other databases, along with manual searches. Articles written (or translated) in English and French and published between 1 January 1980 and 31 October 2013 will be eligible for inclusion in this review. The primary outcomes will be TB knowledge, attitudes and awareness, healthcare-seeking behaviour and service utilisation. The secondary outcomes will include stigma and discrimination against people with TB and the costs of the interventions. We will investigate clinical and statistical heterogeneity and pool studies judged to be clinically and statistically homogeneous. Relative risks will be calculated for dichotomous outcomes and mean differences for continuous outcomes, both with their corresponding 95% CIs.
Ethics and dissemination
The systematic review will use data that is not linked to individuals. The review findings may have implications for clinical practice and future research, and will be disseminated electronically and in print through peer-reviewed publications.
Protocol registration number
PUBLIC HEALTH; BIOTECHNOLOGY & BIOINFORMATICS
Understanding the link between vaccine immunogenicity and efficacy is currently a major focus in HIV research. Consequently, recent developments in the HIV-1 vaccine field have led to a closer look at immune responses to known efficacious vaccines. We undertook a study to explore clinical predictors of vaccine efficacy following recombinant hepatitis B (rHBV) vaccination in a cohort of HIV-uninfected, hepatitis B virus naïve women living in a peri-urban setting in Cape Town. Our aim was to define host biological risk factors associated with lack of vaccine uptake. We found a significant association (p=0.009) between body mass index (BMI) and lack of vaccine-specific IgG titre (<10mIU/mL). Obese individuals (BMI ≥ 30kg/m2) were significantly more likely to be non-responders following 2 rHBV vaccine doses (Adjusted Odds Ratio of 8.75; p=0.043). There was no observed association between vaccine responses and age, method of contraception or time from vaccination to antibody measurement. These data suggest that obesity-associated factors interfere with vaccine immunogenicity and possible efficacy.
Healthcare workers (HCWs) in Africa typically receive little or no training in the healthcare needs of men who have sex with men (MSM), limiting the effectiveness and reach of population-based HIV control measures among this group. We assessed the effect of a web-based, self-directed sensitivity training on MSM for HCWs (www.marps-africa.org), combined with facilitated group discussions on knowledge and homophobic attitudes among HCWs in four districts of coastal Kenya.
We trained four district “AIDS coordinators” to provide a two-day training to local HCWs working at antiretroviral therapy-providing facilities in coastal Kenya. Self-directed learning supported by group discussions focused on MSM sexual risk practices, HIV prevention and healthcare needs. Knowledge was assessed prior to training, immediately after training and three months after training. The Homophobia Scale assessed homophobic attitudes and was measured before and three months after training.
Seventy-four HCWs (68% female; 74% clinical officers or nurses; 84% working in government facilities) from 49 health facilities were trained, of whom 71 (96%) completed all measures. At baseline, few HCWs reported any prior training on MSM anal sexual practices, and most HCWs had limited knowledge of MSM sexual health needs. Homophobic attitudes were most pronounced among HCWs who were male, under 30 years of age, and working in clinical roles or government facilities. Three months after training, more HCWs had adequate knowledge compared to baseline (49% vs. 13%, McNemar's test p<0.001); this was most pronounced in those with clinical or administrative roles and in those from governmental health providers. Compared to baseline, homophobic attitudes had decreased significantly three months after training, particularly among HCWs with high homophobia scores at baseline, and there was some evidence of correlation between improvements in knowledge and reduction in homophobic sentiment.
Scaling up MSM sensitivity training for African HCWs is likely to be a timely, effective and practical means to improve relevant sexual health knowledge and reduce personal homophobic sentiment among HCWs involved in HIV prevention, testing and care in sub-Saharan Africa.
sensitivity training; MSM behaviour; Homophobia Scale; homoprejudice; healthcare workers; Kenya
Men who have sex with men (MSM) in Cape Town's townships remain in need of targeted HIV-prevention services. In 2012, a pilot community-based HIV-prevention programme was implemented that aimed to reach MSM in five Cape Town townships, disseminate HIV-prevention information and supplies, and promote the use of condoms and HIV services.
Convenience sampling was used to recruit self-identified MSM who were 18 years old or older in five Cape Town townships. The six-month pilot programme trained five community leaders who, along with staff, provided HIV-prevention information and supplies to MSM through small-group meetings, community-based social activities and inter-community events. After the completion of the pilot programme, in-depth interviews and focus group discussions (FGDs) were conducted with a subset of conveniently sampled participants and with each of the community leaders. Qualitative data were then analyzed thematically.
Overall, 98 mostly gay-identified black MSM consented to participate, 57 community-based activities were facilitated and 9 inter-community events were conducted. Following their enrolment, 60% (59/98) of participants attended at least one pilot activity. Of those participants, 47% (28/59) attended at least half of the scheduled activities. A total of 36 participants took part in FGDs, and five in-depth interviews were completed with community leaders. Participants reported gaining access to MSM-specific HIV-prevention information, condoms and water-based lubricant through the small-group meetings. Some participants described how their feelings of loneliness, social isolation, self-esteem and self-efficacy were improved after taking part.
The social activities and group meetings were viable strategies for disseminating HIV-prevention information, condoms and water-based lubricant to MSM in this setting. Many MSM were also able to receive social support, reduce social isolation and improve their self-esteem. Further research is needed to explore factors affecting attendance and the sustainability of these activities. Perspectives of MSM who did not attend pilot activities regularly were not equally represented in the final qualitative interviews, which could bias the findings. The use of community-based activities and small-group meetings should be explored further as components to ongoing HIV-prevention interventions for MSM in this setting.
community-based; self-esteem; stigma; African men who have sex with men (MSM); social network; outreach
HIV counseling and testing may serve as an entry point for non-communicable disease screening.
To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit.
A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined.
Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic.
Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care.
HIV-infected individuals have an increased risk of age-related morbidity despite antiretroviral treatment (ART). Several anatomic and functional ophthalmological parameters are associated with increasing chronological age. These may, therefore, potentially serve as biomarkers of ageing. We investigated associations between ocular parameters (lens density, retinal vessel calibre, corneal endothelium and retinal nerve fibre layer thickness) and two ‘cellular’ biomarkers of ageing (leukocyte telomere length and CDKN2A expression) and with frailty in a cross-sectional study of 216 HIV-infected individuals. All ocular parameters, telomere length and frailty were associated with chronological age, whereas CDKN2A expression was not. Retinal venular calibre and lens density were associated with shorter telomere length (p-trend=0.04, and 0.08, respectively), whereas CDKN2A expression and frailty status were not associated with ocular parameters. Longitudinal studies are warranted to assess the integration of retinal vascular calibre and lens density with systemic markers to develop an overall index of biological ageing in HIV infection.
Telomeres; CDKN2A; lens density; retinal vessel calibre; HIV
tuberculin skin test; HIV; TB transmission; children; annual risk of TB infection
The linkage and barriers of linkage to facility-based HIV care from a mobile HIV testing unit have not previously been described.
A stratified random sample (N=192) was drawn of all eligible, newly-diagnosed HIV-infected individuals with a laboratory CD4 count result on a mobile unit between August 2008 and December 2009. All individuals with CD4 counts ≤ 350 cells/μl and 30% of individuals with CD4 counts > 350 cells/μl were sampled. Linkage to care was assessed during April to June 2010 in those that received their CD4 count result. A participant who accessed HIV care at least once after testing was regarded as having linked to care. Binomial regression models were used to identify clinical and socio-demographic factors associated with receiving a CD4 count result and linking to care.
Forty-three (27%) individuals did not receive their CD4 count result. A lower CD4 count, being female and the availability of a phone number increased the likelihood of receiving this result. Follow-up was attempted in the remaining 145 individuals. Ten refused to participate and contact was unsuccessful in 42.4%. Linkage was 100% in patients with CD4 counts ≤ 200 cells/μl, 66.7% in individuals with CD4 counts of 201-350 cells/μl and 36.4% in those with CD4 counts > 350 cells/μl. A lower CD4 count, disclosure, presence of TB symptoms and unemployment increased the likelihood of linking to care.
Linkage to care was best among those eligible for ART. Interventions designed at improving linkage among employed individuals are urgently warranted.
Mobile HIV testing unit; linkage to HIV and ART care; barriers to linkage to HIV care
HAART; tuberculosis; isoniazid; prevention; antiretroviral; Africa
In Southern Africa, men access HIV counseling and testing (HCT) services less than women. Innovative strategies are needed to increase uptake of testing among men. This study assessed the effectiveness of incentivized mobile HCT in reaching unemployed men in Cape Town, South Africa.
A retrospective analysis of HCT data collected between August 2008 and August 2010 from adult men accessing clinic-based stationary and non-incentivized and incentivized mobile services. Data from these three services were analyzed using descriptive statistics and log-binomial regression models.
A total of 9416 first time testers were included in the analysis: 708 were clinic-based, 4985 were non-incentivized and 3723 incentivized mobile service testers. A higher HIV prevalence was observed among men accessing incentivized mobile testing 16.6% (617/3723) compared to those attending non-incentivized mobile 5.5% (277/4985)] and clinic-based services 10.2% (72/708)]. Among men testing at the mobile service, greater proportions of men receiving incentives were self-reported first-time testers (60.1% vs. 42.0%) and had advanced disease (14.9% vs. 7.5%) compared to men testing at non-incentivized mobile services. Furthermore, compared to the non-incentivized mobile service, the incentivized service was associated with a 3-fold greater yield of newly diagnosed HIV infections. This strong association persisted in analyses adjusted for age and first-time versus repeat testing (RR 2.33 95% CI 2.03–2.57]; p<0.001).
These findings suggest that incentivized mobile testing services may reach more previously untested men and significantly increase detection of HIV infection in men.
voluntary counseling and testing; mobile services; HIV; incentives; sub-Saharan Africa
To determine the short-term and long-term risks of tuberculosis (TB) associated with CD4 cell recovery during antiretroviral therapy (ART).
Observational community-based ART cohort in South Africa.
TB incidence was determined among patients (n = 1480) receiving ART for up to 4.5 years in a South African community-based service. Updated CD4 cell counts were measured 4-monthly. Person-time accrued within a range of CD4 cell count strata (CD4 cell strata) was calculated and used to derive CD4 cell-stratified TB rates. Factors associated with incident TB were identified using Poisson regression models.
Two hundred and three cases of TB were diagnosed during 2785 person-years of observation (overall incidence, 7.3 cases/100 person-years). During person-time accrued within CD4 cell strata 0–100, 101–200, 201–300, 301–400, 401–500 and more than 500 cells/µl unadjusted TB incidence rates were 16.8, 9.3, 5.5, 4.6, 4.2 and 1.5 cases/100 person-years, respectively (P < 0.001). During early ART (first 4 months), adjusted TB rates among those with CD4 cell counts 0–200 cells/µl were 1.7-fold higher than during long-term ART (P = 0.026). Updated CD4 cell counts were the only patient characteristic independently associated with long-term TB risk.
Updated CD4 cell counts were the dominant predictor of TB risk during ART in this low-resource setting. Among those with baseline CD4 cell counts less than 200 cells/µl, the excess adjusted risk of TB during early ART was consistent with ‘unmasking’ of disease missed at baseline screening. TB incidence rates at CD4 cell counts of 200–500 cells/µl remained high and adjunctive interventions are required. TB prevention would be improved by ART policies that minimized the time patients spend with CD4 cell counts below a threshold of 500 cells/µl.
Africa; antiretroviral; CD4 cell; HIV; immune reconstitution; resource-limited country; tuberculosis
Antiretroviral therapy (ART) has been proposed as an intervention for reducing tuberculosis (TB) burdens in areas with high HIV prevalence. However, little data is available on the impact of ART on population-level TB.
Trends in adult TB case fatality and notifications were assessed prior to and during increasing ART coverage in a well-defined peri-urban community, from 1997 to 2008. Mean changes in TB rates were measured using linear autoregression models. ART coverage increased from 1% in 2003, to 5%, 13% and 21% of HIV-infected population in 2004, 2005 and 2008 respectively.
From 1997 to end of 2004 TB notification rates increased by an average of 187 cases/100,000/yr (p<0.001), reaching a peak of 2,536/100,000 in 2005. From 2005 to 2008, TB notification rates declined by approximately 183 cases/100,000/yr (p<0.001). TB rates were initially stable in HIV-uninfected individuals, but declined moderately from 2005. TB rates declined in HIV-infected adults from 6,513/100,000 in 2005 to 4,741/100,000 in 2008. The predominant decline in TB notifications occurred among HIV-infected patients receiving ART (1,156 cases/100,000/yr) and was less marked in those not receiving ART (416cases/100,000/yr). Similarly, TB case fatality was constant for HIV-uninfected individuals but declined in HIV-infected individuals from 23% in 2002 to 8% in 2008 (p=0.01).
In this community heavily affected by both HIV and TB epidemics, rapid and high ART coverage was associated with significant reductions in TB notifications and TB-associated case fatality.
tuberculosis; notification rates; HIV; antiretroviral; community
Antiretroviral treatment (ART) has altered the spectrum of HIV-related eye disease, resulting in a lower prevalence of retinal opportunistic infections (OIs). However, abnormalities in visual function have been reported in HIV-infected individuals despite effective viral suppression and the absence of retinal OIs. These changes may be mediated by an HIV-associated ‘neuroretinal disorder’, characterized by changes in the retinal nerve fibre layer (RNFL). HIV infection may also be associated with accelerated biological aging. The aim of this study was to investigate the relationships between contrast sensitivity, RNFL thickness, HIV infection and frailty in South African adults.
Case-control study of 225 HIV-infected individuals without retinal OIs and 203 gender/age-matched HIV-seronegative individuals. Peri-papillary RNFL thickness was determined with spectral domain optical coherence tomography in four quadrants. CS was measured using a Pelli-Robson chart. Frailty was assessed using standard criteria. Multivariable linear and logistic regression were used to assess associations between HIV status and RNFL/CS and frailty.
The median age of both groups was similar (41.2 vs. 41.9 years, p = 0.37). 88% of HIV-infected individuals were receiving ART and their median CD4 count was 468 cells/μl. Adjusted CS score was lower in HIV-infected participants compared to HIV-seronegative individuals (1.76 vs. 1.82, p = 0.002). Independent predictors of poor CS in the HIV-infected group were positive frailty status and current HIV viral load >2 log copies/ml. Lower CS score was also associated with thin temporal RNFL in HIV-infected individuals (p = 0.04). Superior quadrant RNFL thickness was greatest in ART-naïve participants relative to the HIV-uninfected group (p-trend = 0.04). Longer ART duration was associated with thinning of inferior and nasal RNFL quadrants (p-trend = 0.03 and 0.04, respectively).
Contrast sensitivity is reduced in HIV-infected individuals and functionally associated with frailty and unsuppressed viraemia. This may reflect structural changes in the RNFL that are evident despite the absence of OIs.
To assess sustainability of programmatic outcomes in a community-based antiretroviral therapy (ART) service in South Africa during 7 years scale-up.
Prospective cohort of treatment-naïve patients aged ≥15 years enrolled between 2002 and 2008. Data were analyzed by calendar period of ART initiation using time to-event analysis and logistic regression.
ART was initiated by 3162 patients (67% female, median age 34 years) who were followed-up for a median of 2.4 years (IQR,1.2-3.8). After 6 years, the cumulative probability of death and loss to follow-up (LTFU) was 37.4%. The probabilities of transfer-out to another ART service and of virological failure were 21.6% and 23.1%, respectively. Low mortality risk and excellent virological and immunological responses during the first year of ART were not associated with calendar period of ART initiation. In contrast, risk of LTFU and virological failure both increased between successive calendar periods in unadjusted and adjusted analyses. The number of patients per member of clinic staff increased markedly over time.
Successful early outcomes (low mortality and good immunological and virological responses) were sustained between sequential calendar periods during 7 years of scale-up. In contrast, the increasing cumulative probabilities of LTFU or virological failure may reflect decreasing capacity to adequately support patients long-term as clinic case-load escalated.
Antiretroviral; outcomes; mortality; loss to follow-up; virological failure; Africa
To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART).
Observational community-based ART cohort in South Africa.
CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates.
Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300– 399, 400–499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART.
Africa; antiretroviral; antiretroviral therapy; CD4; death; HIV; immune reconstitution; immune recovery; mortality