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1.  Enrolling Adolescents in Research on HIV and Other Sensitive Issues: Lessons from South Africa 
PLoS Medicine  2006;3(7):e180.
Jerome Singh and colleagues present the ethical and legal challenges surrounding the enrollment of adolescents in HIV observational studies and other types of sensitive research.
doi:10.1371/journal.pmed.0030180
PMCID: PMC1435780  PMID: 16608384
2.  Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial 
Trials  2014;15(1):496.
Background
The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial.
Methods/design
This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision.
Discussion
This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa.
Trial registration
This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012.
doi:10.1186/1745-6215-15-496
PMCID: PMC4300828  PMID: 25527071
South Africa; HIV prevention; Microbicide; Tenofovir gel; Health systems strengthening; Implementation
3.  Low adverse event rates following voluntary medical male circumcision in a high HIV disease burden public sector prevention programme in South Africa 
Introduction
The provision of voluntary medical male circumcision (VMMC) services was piloted in three public sector facilities in a high HIV disease burden, low circumcision rate province in South Africa to inform policy and operational guidance for scale-up of the service for HIV prevention. We report on adverse events (AEs) experienced by clients following the circumcision procedure.
Methods
Prospective recruitment of HIV-negative males aged 12 and older volunteering to be circumcised at three select public health facilities in KwaZulu-Natal between November 2010 and May 2011. Volunteers underwent standardized medical screening including a physical assessment prior to the surgical procedure being performed. AEs were monitored at three time intervals over a 21-day period post-operatively to determine safety outcomes in this pilot demonstration programme.
Results
A total of 602 volunteers participated in this study. The median age of the volunteers was 22 years (range 12–56). Most participants (75.6%) returned for the 48-hour post-operative visit; 51.0% for day seven visit and 26.1% for the 21st day visit. Participants aged 20–24 were most likely to return. The AE rate was 0.2% intra-operatively. The frequency of moderate AEs was 0.7, 0.3 and 0.6% at 2-, 7- and 21-day visits, respectively. The frequency of severe AEs was 0.4, 0.3 and 0.6% at 2-, 7- and 21-day visits, respectively. Swelling and wound infection were the most common AEs with mean appearance duration of seven days. Clients aged between 35 and 56 years presented with most AEs (3.0%).
Conclusions
VMMC can be delivered safely at resource-limited settings. The intensive three-visit post-operative review practice may be unfeasible due to high attrition rates over time, particularly amongst older men.
doi:10.7448/IAS.17.1.19275
PMCID: PMC4236629  PMID: 25406951
medical male circumcision; HIV prevention; adverse events; follow-up visit
4.  ARV-based HIV prevention for women – where we are in 2014 
Journal of the International AIDS Society  2014;17(3Suppl 2):19154.
Women continue to be at special risk for HIV acquisition due to a complex mix of biological, behavioural, structural, cultural and social factors, with unacceptable rates of new infection. Scientific advances over the past decade have highlighted the use of antiretroviral (ARV) drugs as pre-exposure prophylaxis (PrEP) to prevent HIV acquisition (sexually, parenterally and vertically) and ARV treatment (ART) for HIV-positive patients to prevent onward transmission (treatment as prevention – TasP). This paper reviews the evidence base for PrEP and TasP, describes new products in development and the need to translate research findings into programmes with impact at the population level.
doi:10.7448/IAS.17.3.19154
PMCID: PMC4164013  PMID: 25224614
HIV; AIDS; antiretroviral agents; women; HIV prevention; HIV treatment; PrEP
5.  Limited HIV-1 Superinfection in Seroconverters from the CAPRISA 004 Microbicide Trial 
Journal of Clinical Microbiology  2014;52(3):844-848.
HIV-1 superinfection (SI) occurs when an infected individual acquires a distinct new viral strain. The rate of superinfection may be reflective of the underlying HIV risk in a population. The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 clinical trial demonstrated that women who used a tenofovir-containing microbicide gel had lower rates of HIV infection than women using a placebo gel. Women who contracted HIV-1 during the trial were screened for the occurrence of superinfection by next-generation sequencing of the viral gag and env genes. There were two cases (one in each trial arm) of subtype C superinfection identified from the 76 women with primary infection screened at two time points (rate of superinfection, 1.5/100 person-years). Both women experienced a >0.5-log increase in viral load during the window when superinfection occurred. The rate of superinfection was significantly lower than the overall primary HIV incidence in the microbicide trial (incidence rate ratio [IRR], 0.20; P = 0.003). The women who seroconverted during the trial reported a significant increase in sexual contact with their stable partner 4 months after seroconversion (P < 0.001), which may have lowered the risk of superinfection in this population. The lower frequency of SI compared to the primary incidence is in contrast to a report from a general heterosexual African population but agrees with a study of high-risk women in Kenya. A better understanding of the rate of HIV superinfection could have important implications for ongoing HIV vaccine research.
doi:10.1128/JCM.03143-13
PMCID: PMC3957790  PMID: 24371237
6.  Honing in on enteric fever 
eLife  2014;3:e03545.
The use of metabolomics could lead to improved diagnostics for enteric fever.
doi:10.7554/eLife.03545
PMCID: PMC4077202  PMID: 24986861
metabolites; mass spectrometry; enteric fever; typhoid; Salmonella Typhi; Salmonella Paratyphi A; human
7.  Neither microbial translocation nor TLR responsiveness are likely explanations for pre-existing immune activation in women who subsequently acquired HIV in CAPRISA004 
Journal of acquired immune deficiency syndromes (1999)  2013;63(3):10.1097/QAI.0b013e31828e604b.
Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA004. Identifying the cause/s of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14 and intestinal fatty-acid binding protein did not differ between subjects who did or did not subsequently acquire HIV, nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV-acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4 or 7/8 agonists. Further studies are required.
doi:10.1097/QAI.0b013e31828e604b
PMCID: PMC3683111  PMID: 23481666
HIV; microbial translocation; LPS; sCD14; I-FABP; TLR2; TLR4; TLR7/8; immune activation
8.  Antiretroviral prophylaxis: a defining moment for HIV prevention 
Lancet  2011;378(9809):e23-e25.
doi:10.1016/S0140-6736(11)61136-7
PMCID: PMC3253379  PMID: 21771566
9.  Sustainability of task-shifting for antiretroviral treatment 
Lancet  2012;380(9857):1907-1908.
doi:10.1016/S0140-6736(12)62110-2
PMCID: PMC3616248  PMID: 23200500
10.  Innate Immune Activation Enhances HIV Acquisition in Women, Diminishing the Effectiveness of Tenofovir Microbicide Gel 
The Journal of Infectious Diseases  2012;206(7):993-1001.
The antiretroviral agent, tenofovir, formulated as a vaginal microbicide gel, reduces human immunodeficiency virus (HIV) acquisition by 39% in women. This study assessed the role of preexisting immune activation in HIV acquisition in women from the CAPRISA 004 trial, to identify potential strategies to increase the effectiveness of tenofovir gel. Systemic cytokine and cellular immune mediators (platelets and natural killer [NK] cells) were assessed in women at high risk for HIV assigned to either tenofovir or placebo gel in the CAPRISA 004 trial. Notwithstanding tenofovir gel use, women who acquired HIV had significantly higher systemic innate immune activation prior to infection than women who remained uninfected. Activation of both soluble (cytokine) and cellular (NK cells) immune mediators were associated with HIV acquisition, individually or in combination. Hence, an innate immune activation suppressant could be added to tenofovir gel as a potential combination gel strategy in developing the next generation of higher efficacy antiretroviral microbicides.
doi:10.1093/infdis/jis465
PMCID: PMC3501691  PMID: 22829639
11.  Ratio of Monocytes to Lymphocytes in Peripheral Blood Identifies Adults at Risk of Incident Tuberculosis Among HIV-Infected Adults Initiating Antiretroviral Therapy 
The Journal of Infectious Diseases  2013;209(4):500-509.
Background. Eight decades ago, the ratio of monocytes to lymphocytes (hereafter, the “ML ratio”) was noted to affect outcomes of mycobacterial infection in rabbits. Recent transcriptomic studies support a role for relative proportions of myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in peripheral blood is known to be governed by hematopoietic stem cells with distinct biases.
Methods. The predictive value of the baseline ML ratio was modeled in 2 prospective cohorts of HIV-infected adults starting cART in South Africa (primary cohort, 1862 participants; replication cohort, 345 participants). Incident tuberculosis was diagnosed with clinical, radiographic, and microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses and Cox proportional hazards modeling were conducted.
Results. The incidence rate of tuberculosis differed significantly by baseline ML ratio: 32.61 (95% confidence interval [CI], 15.38–61.54), 16.36 (95% CI, 12.39–21.23), and 51.80 (95% CI, 23.10–101.71) per 1000 patient-years for ML ratios of less than the 5th percentile, between the 5th and 95th percentiles, and greater than the 95th percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte counts alone were associated with tuberculosis. After adjustment for sex, World Health Organization human immunodeficiency virus disease stage, CD4+ T-cell counts, and previous history of tuberculosis, hazards of disease were significantly higher for patients with ML ratios of less than the 5th percentile or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39–4.40; P = .002).
Conclusions. The ML ratio may be a useful, readily available tool to stratify the risk of tuberculosis and suggests involvement of hematopoietic stem cell bias in tuberculosis pathogenesis.
doi:10.1093/infdis/jit494
PMCID: PMC3903371  PMID: 24041796
tuberculosis; HIV; combination antiretroviral therapy; monocytes; lymphocytes; ML ratio
12.  Genital Tract Inflammation During Early HIV-1 Infection Predicts Higher Plasma Viral Load Set Point in Women 
The Journal of Infectious Diseases  2012;205(2):194-203.
Background. The biggest challenge in human immunodeficiency virus type 1 (HIV-1) prevention in Africa is the high HIV-1 burden in young women. In macaques, proinflammatory cytokine production in the genital tract is necessary for target cell recruitment and establishment of simian immunodeficiency virus (SIV) infection following vaginal inoculation. The purpose of this study was to assess if genital inflammation during early HIV-1 infection predisposes women to rapid disease progression.
Methods. Inflammatory cytokine concentrations were measured in cervicovaginal lavage (CVL) from 49 women 6, 17, 30, and 55 weeks after HIV-1 infection and from 22 of these women before infection. Associations between genital inflammation and viral load set point and blood CD4 cell counts 12 months after infection were investigated.
Results. Elevated genital cytokine concentrations 6 and 17 weeks after HIV-1 infection were associated with higher viral load set points and, to a lesser extent, with CD4 depletion. CVL cytokine concentrations during early infection did not differ relative to preinfection but were elevated in women who had vaginal discharge, detectable HIV-1 RNA in their genital tracts, and lower blood CD4 counts.
Conclusion. Genital inflammation during early HIV-1 infection was associated with higher viral load set point and CD4 depletion, which are markers of rapid disease progression. Strategies aimed at reducing genital inflammation during early HIV-1 infection may slow disease progression.
doi:10.1093/infdis/jir715
PMCID: PMC3244362  PMID: 22190580
13.  Integration of Antiretroviral Therapy with Tuberculosis Treatment 
The New England journal of medicine  2011;365(16):1492-1501.
Background
We previously reported that integrating antiretroviral therapy (ART) with tuberculosis treatment reduces mortality. However, optimal time to initiate ART during tuberculosis treatment remains contentious.
Methods
To address this, we conducted a 3-arm, open-label randomized controlled trial in South Africa in acid-fast bacilli smear positive patients (n=642) with HIV and CD4+ counts <500 cells/mm3. Findings on the early therapy group (ART initiated within 4 weeks of tuberculosis treatment initiation, n=214) and late therapy group (ART initiated within the first 4 weeks of the continuation phase of tuberculosis treatment, n=215) are presented here.
Results
Median CD4+ count and viral load at baseline was 150 cells/mm3 and 161000 copies/ml, being similar in both groups. Incidence rate of AIDS or death was 6.9 (18/259.4) and 7.8 (19/244.2) per 100 person-years in the early and late therapy groups respectively (Incidence Rate Ratio (IRR)=0.89; 95%Confidence Interval (95%CI): 0.44,1.79; P=0.73). However, in patients with CD4+ counts <50 cells/mm3, the incidence rates of AIDS or death were 8.5 (early) and 26.3 (late) per 100 person-years (IRR=0.32; 95%CI: 0.07,1.13; P=0.06). Immune reconstitution inflammatory syndrome (IRIS) incidence rates were 20.2 (early) and 7.7 (late) per 100 person-years (IRR=2.62; 95%CI: 1.48,4.82; P<0.001). Adverse events requiring antiretroviral drug switches occurred in 10 (early) and 1 (late) patients (P=0.006).
Conclusions
The benefits of AIDS-free survival balanced against the risks of IRIS and ART-related adverse events, support early ART initiation in patients with CD4+ counts <50 cells/mm3 and deferred ART initiation to the continuation phase of tuberculosis treatment when CD4+ counts are higher.
doi:10.1056/NEJMoa1014181
PMCID: PMC3233684  PMID: 22010915
14.  HIV prevalence among high school learners - opportunities for schools-based HIV testing programmes and sexual reproductive health services 
BMC Public Health  2012;12:231.
Background
Young girls in sub Saharan Africa are reported to have higher rates of human immunodeficiency virus (HIV) infection compared to boys in the same age group. Knowledge of HIV status amongst high schools learners provides an important gateway to prevention and treatment services. This study aimed at determining the HIV prevalence and explored the feasibility of HIV testing among high school learners.
Methods
Between September 2010 and February 2011, a linked, anonymous cross-sectional survey was conducted in two public sector high schools in the rural KwaZulu-Natal midlands. Following written informed consent, dried blood spot samples (DBS) were collected and tested for HIV. The overall and age-specific HIV prevalence were compared with select demographic variables.
Results
The HIV prevalence in learners aged 12 to 25 in school A was 4.7% (95% CI 2.8-6.5) compared to 2.5% (95% CI 1.6-3.5) in school B, (p = 0.04). Whilst the HIV prevalence was similar for boys at 1.3% (95% CI 0-2.8) in school A and 1.7% (95% CI 0.5-2.8) in school B, the prevalence in girls was consistently higher and was 7.7% (95% CI 4.5-10.9) in school A and 3.2% (95% CI 1.8-4.6) in school B. The age-specific HIV prevalence in girls increased 1.5 to 2 fold for each two year age category, while for boys the prevalence was stable across all age groups.
Conclusions
The high HIV prevalence in female learners underscores the importance of sexual reproductive health and schools-based HIV testing programs as an important gateway to prevention and treatment services.
doi:10.1186/1471-2458-12-231
PMCID: PMC3359203  PMID: 22439635
Young girls; HIV prevalence; surveillance
15.  Gender-sensitive reporting in medical research 
Sex and gender differences influence the health and wellbeing of men and women. Although studies have drawn attention to observed differences between women and men across diseases, remarkably little research has been pursued to systematically investigate these underlying sex differences. Women continue to be underrepresented in clinical trials, and even in studies in which both men and women participate, systematic analysis of data to identify potential sex-based differences is lacking. Standards for reporting of clinical trials have been established to ensure provision of complete, transparent and critical information. An important step in addressing the gender imbalance would be inclusion of a gender perspective in the next Consolidated Standards of Reporting Trials (CONSORT) guideline revision. Uniform Requirements for Manuscripts Submitted to Biomedical Journals, as a set of well-recognized and widely used guidelines for authors and biomedical journals, should similarly emphasize the ethical obligation of authors to present data analyzed by gender as a matter of routine. Journal editors are also promoters of ethical research and adequate standards of reporting, and requirements for inclusion of gender analyses should be integrated into editorial policies as a matter of urgency.
doi:10.1186/1758-2652-15-11
PMCID: PMC3313880  PMID: 22400977
16.  Experience in international clinical research: the HIV Prevention Trials Network 
Clinical investigation  2011;1(12):1609-1618.
The HIV Prevention Trials Network (HPTN) is supported by the NIH to conduct randomized clinical trials to assess the efficacy of HIV prevention strategies and technologies to reduce HIV transmission between adults. A special focus of attention is on the use of antiretroviral drugs to prevent HIV transmission, both by reducing infectiousness among HIV-infected persons taking combination antiretroviral therapy (cART) and also by reducing susceptibility among HIV-uninfected persons taking antiretrovirals for pre-exposure prophylaxis. Studies may be developmental in nature to assess novel ideas for interventions or for assessing trial feasibility. However, pivotal efficacy trials to test HIV-specific prevention strategies and technologies are the main HPTN priority. Examples include a major protocol investigating the impact of expanded testing and linkage to care on HIV surveillance indicators in the USA (HPTN 065). Another protocol is addressing similar issues while also investigating how combinations of prevention approaches are best deployed to make a community-level impact in southern Africa (HPTN 071). HPTN 068 is evaluating a novel conditional cash transfer structural intervention to increase school completion rates in young girls and thereby reduce their HIV risk. Studies outside the US address the epidemic in most at-risk populations and include an assessment of opiate agonist therapy to reduce risk of HIV seroconversion among injection drug users (HTPN 058), methods to increase HIV testing rates (HTPN 043), as well as methods for reducing high-risk behaviors, and increasing adherence to cART in HIV-infected individuals (HPTN 062 and HPTN 063, respectively). The recent HPTN 052 study demonstrated that a 96% reduction in HIV transmission could be achieved between serodiscordant sexual partners by providing the infected partners with cART at a CD4+ cell count (350–550/µl) above the level that would usually qualify them for therapy in low- and middle-income countries. The immediate relevance to public health policy showcased in these trials is a paradigm for the HPTN: design and conduct of clinical trials using available licensed tools that can be rapidly translated for implementation (‘Prevention NOW!’).
doi:10.4155/cli.11.156
PMCID: PMC3281583  PMID: 22348195
developing country; HIV/AIDS; prevention; randomized clinical trial; research collaboration; research infrastructure
17.  Understanding Methods for Estimating HIV-Associated Maternal Mortality 
Journal of Pregnancy  2011;2012:958262.
The impact of HIV on maternal mortality and more broadly on the health of women, remains poorly documented and understood. Two recent reports attempt to address the conceptual and methodological challenges that arise in estimating HIV-related maternal mortality and trends. This paper presents and compares the methods and discusses how they affect estimates at global and regional levels. Country examples of likely patterns of mortality among women of reproductive age are provided to illustrate the critical interactions between HIV and complications of pregnancy in high-HIV-burden countries. The implications for collaboration between HIV and reproductive health programmes are discussed, in support of accelerated action to reach the Millennium Development Goals and improve the health of women.
doi:10.1155/2012/958262
PMCID: PMC3182332  PMID: 21966594
18.  Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women 
Science (New York, N.Y.)  2010;329(5996):1168-1174.
The CAPRISA 004 trial assessed effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n=445) with placebo gel (n=444) in sexually active, HIV-uninfected 18-40 year-old women in urban and rural KwaZulu-Natal, South Africa HIV serostatus, safety, sexual behavior and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (wy), i.e. person time of study observation, (38/680.6wy) compared to 9.1 per 100 wy (60/660.7wy) in the placebo gel arm (Incidence Rate Ratio (IRR)=0.61; p=0.017).In high adherers (gel adherence >80%), HIV incidence was 54% lower (p=0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50-80%) and low adherers (gel adherence < 50%) the HIV incidence reduction was 38% and 28% respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconvertors. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.
doi:10.1126/science.1193748
PMCID: PMC3001187  PMID: 20643915
19.  Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression 
AIDS (London, England)  2010;24(6):819-831.
Background
Both T cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown.
Objectives
To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression.
Design
Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection.
Methods
The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set-point 12 months post-infection and time taken for CD4 counts to fall below 350 cells/μl were determined using multivariate and Cox proportional-hazards regression.
Results
We found that the concentrations of 5 plasma cytokines, IL-12p40, IL-12p70, IFN-γ, IL-7 and IL-15, in women with acute infection predicted 66% of the variation in viral load set-point 12 months post infection. IL-12p40, IL-12p70 and IFN-γ were significantly associated with lower viral load whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and GM-CSF during acute infection were associated with maintenance of CD4 counts above 350 cells/μl while IL-1α, eotaxin and IL-7 were associated with more rapid CD4 loss.
Conclusions
A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.
doi:10.1097/QAD.0b013e3283367836
PMCID: PMC3001189  PMID: 20224308
HIV-1; cytokines; acute infection; viral load; disease progression
20.  HIV-Associated Tuberculosis 
The intersecting HIV and Tuberculosis epidemics in countries with a high disease burden of both infections pose many challenges and opportunities. For patients infected with HIV in high TB burden countries, the diagnosis of TB, ARV drug choices in treating HIV-TB coinfected patients, when to initiate ARV treatment in relation to TB treatment, managing immune reconstitution, minimising risk of getting infected with TB and/or managing recurrent TB, minimizing airborne transmission, and infection control are key issues. In addition, given the disproportionate burden of HIV in women in these settings, sexual reproductive health issues and particular high mortality rates associated with TB during pregnancy are important. The scaleup and resource allocation to access antiretroviral treatment in these high HIV and TB settings provide a unique opportunity to strengthen both services and impact positively in meeting Millennium Development Goal 6.
doi:10.1155/2011/585919
PMCID: PMC2943082  PMID: 20871843
21.  HIV infection and tuberculosis in South Africa: an urgent need to escalate the public health response 
Lancet  2009;374(9693):921-933.
One of the greatest challenges facing post-apartheid South Africa is the control of the concomitant HIV and tuberculosis epidemics. HIV continues to spread relentlessly, and tuberculosis has been declared a national emergency. In 2007, South Africa, with 0·7% of the world’s population, had 17% of the global burden of HIV infection, and one of the world’s worst tuberculosis epidemics, compounded by rising drug resistance and HIV co-infection. Until recently, the South African Government’s response to these diseases has been marked by denial, lack of political will, and poor implementation of policies and programmes. Nonetheless, there have been notable achievements in disease management, including substantial improvements in access to condoms, expansion of tuberculosis control efforts, and scale-up of free antiretroviral therapy (ART). Care for acutely ill AIDS patients and long-term provision of ART are two issues that dominate medical practice and the health-care system. Decisive action is needed to implement evidence-based priorities for the control of the HIV and tuberculosis epidemics. By use of the framework of the Strategic Plans for South Africa for tuberculosis and HIV/AIDS, we provide prioritised four-step approaches for tuberculosis control, HIV prevention, and HIV treatment. Strong leadership, political will, social mobilisation, adequate human and financial resources, and sustainable development of health-care services are needed for successful implementation of these approaches.
doi:10.1016/S0140-6736(09)60916-8
PMCID: PMC2803032  PMID: 19709731
22.  Establishing a Cohort at High Risk of HIV Infection in South Africa: Challenges and Experiences of the CAPRISA 002 Acute Infection Study 
PLoS ONE  2008;3(4):e1954.
Objectives
To describe the baseline demographic data, clinical characteristics and HIV-incidence rates of a cohort at high risk for HIV infection in South Africa as well as the challenges experienced in establishing and maintaining the cohort.
Methodology/Principle Findings
Between August 2004 and May 2005 a cohort of HIV-uninfected women was established for the CAPRISA 002 Acute Infection Study, a natural history study of HIV-1 subtype C infection. Volunteers were identified through peer-outreach. The cohort was followed monthly to determine HIV infection rates and clinical presentation of early HIV infection. Risk reduction counselling and male and female condoms were provided. After screening 775 individuals, a cohort of 245 uninfected high-risk women was established. HIV-prevalence at screening was 59.6% (95% CI: 55.9% to 62.8%) posing a challenge in accruing HIV-uninfected women. The majority of women (78.8%) were self-identified as sex-workers with a median of 2 clients per day. Most women (95%) reported more than one casual sexual partner in the previous 3 months (excluding clients) and 58.8% reported condom use in their last sexual encounter. Based on laboratory testing, 62.0% had a sexually transmitted infection at baseline. During 390 person-years of follow-up, 28 infections occurred yielding seroincidence rate of 7.2 (95% CI: 4.5 to 9.8) per 100 person-years. Despite the high mobility of this sex worker cohort retention rate after 2 years was 86.1%. High co-morbidity created challenges for ancillary care provision, both in terms of human and financial resources.
Conclusions/Significance
Challenges experienced were high baseline HIV-prevalence, lower than anticipated HIV-incidence and difficulties retaining participants. Despite challenges, we have successfully accrued this cohort of HIV-uninfected women with favourable retention, enabling us to study the natural history of HIV-1 during acute HIV-infection. Our experiences provide lessons for others establishing similar cohorts, which will be key for advancing the vaccine and prevention research agenda in resource-constrained settings.
doi:10.1371/journal.pone.0001954
PMCID: PMC2278382  PMID: 18414658

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