Neil A Martinson

University of the Witwatersrand, Johannesburg, Gauteng, South Africa

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Publications (43)305.84 Total impact

  • Article: Mortality associated with delays between clinic entry and ART initiation in resource-limited-settings: results of a transition-state model.
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    ABSTRACT: OBJECTIVE:: Estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry-into-care. DESIGN:: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART eligible patients without conducting a randomized trial. METHODS:: We used patient-level data from three South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter we generated probabilities and distributions for Monte Carlo simulations with one week cycles to estimate mortality 52 weeks from clinic entry. RESULTS:: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10 week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells/mm, 12 month mortality increased from 13.3% with no delay compared to 17.0% with a 10 week delay and 22.9% with a 6 month delay. CONCLUSIONS:: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low cost approach with a potential marked impact on mortality.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2013; · 4.43 Impact Factor
  • Article: High Prevalence of Pulmonary Tuberculosis but Low Sensitivity of Symptom Screening among HIV-Infected Pregnant Women in South Africa.
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    ABSTRACT: Symptom screening is a recommended component of intensified case-finding (ICF) for pulmonary tuberculosis (TB) among HIV-infected individuals. Symptomatic individuals are further investigated to either exclude or diagnose pulmonary TB, thus reducing the number of individuals requiring costly laboratory investigation. Those with laboratory evaluations negative for pulmonary TB or who lack symptoms may be eligible for antiretroviral therapy (ART) and/or TB isoniazid preventive therapy (IPT). A four-part symptom screen has been recommended by the World Health Organization (WHO) for identifying TB suspects and those unlikely to have TB. A meta-analysis of studies among HIV-infected individuals calculated a sensitivity of 90.1% for the four-part symptoms screen - of any of cough, fever, night sweats, or weight loss - among patients in clinical care, making it an effective tool for identifying most patients with TB. An important population for intensified case-finding not included in that meta-analysis was HIV-infected pregnant women. We undertook a cross-sectional survey among HIV-infected pregnant women receiving prenatal care at community clinics in South Africa. We obtained a four-symptom review and sputum smear microscopy and mycobacterial culture on all participants. Among 1415 women, 226 (16%) had a positive symptom screen, and 35 (2.5%) were newly diagnosed with culture-positive TB. Twelve were on TB treatment at the time of screening, yielding 47 (3.3%) women with prevalent TB. Symptom screening among women without known TB had a sensitivity of 28% and specificity of 84%. The poor performance of symptom screening to identify women with TB suggests that other approaches may be needed for intensified case-finding to be effective for this population.
    PLoS ONE 01/2013; 8(4):e62211. · 4.09 Impact Factor
  • Article: The Clinical and Economic Impact of Genotype Testing at First-line Antiretroviral Therapy Failure for HIV-infected Patients in South Africa.
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    ABSTRACT: Background. In resource-limited settings, genotype testing at virologic failure on first-line antiretroviral therapy (ART) may identify patients with wild-type virus. After adherence counseling, these patients may safely and effectively continue first-line ART, thereby delaying more expensive second-line ART.Methods. We used the Cost-effectiveness of Preventing AIDS Complications (CEPAC) International model of HIV disease to simulate a South African cohort of HIV-infected adults at first-line ART failure. Two strategies were examined: no genotype vs. genotype, assuming availability of protease inhibitor-based second-line ART. Model inputs at first-line ART failure were mean age 38 years, mean CD4 173/µl, and wild-type virus prevalence 20%; genotype cost was $300/test and delay to results, 3 months. Outcomes included life expectancy, per-person costs (2010 US$), and incremental cost-effectiveness ratios ($/years of life saved [YLS]).Results. No genotype had a projected life expectancy of 106.1 months, which with genotype increased to 108.3 months. Per-person discounted lifetime costs were $16,360 and $16,540, respectively. Compared to no genotype, genotype was very cost-effective, by international guidance, at $900/YLS. The cost-effectiveness of genotype was sensitive to prevalence of wild-type virus (very cost-effective when prevalence ≥12%), CD4 at first-line ART failure, and ART efficacy. Genotype-associated delays in care ≥5 months decreased survival and made no genotype the preferred strategy. When the test cost was <$100, genotype became cost-saving.Conclusion. Genotype resistance testing at first-line ART failure is very cost-effective in South Africa. The cost-effectiveness of this strategy will depend on prevalence of wild-type virus and timely response to genotype results.
    Clinical Infectious Diseases 10/2012; · 9.15 Impact Factor
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    Article: Increased regression and decreased incidence of human papillomavirus-related cervical lesions among HIV-infected women on HAART.
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    ABSTRACT: To determine the impact of HAART on incidence, regression, and progression of cytopathological abnormalities in HIV-infected women. Prospective cohort. HIV-infected women (N=1123) from Soweto, South Africa underwent serial cervical smears that were analyzed and reported using the Bethesda System. The results of HAART and non-HAART users were compared using two statistical approaches: a survival analysis assessing risk of incident smear abnormality among women with baseline normal smear results; and analysis with marginal models assessing for an association between HAART use and likelihood of regression/progression in consecutive smears. After multivariate survival analysis, women using HAART with a normal baseline smear were 38% less likely to have an incident smear abnormality during follow-up than nonusers [confidence interval (CI) 0.42-0.91; P=0.01]. Multivariate marginal models analysis identified a significantly increased likelihood (odds ratio 2.61; CI 1.75-3.89; P<0.0001) of regression of cervical lesions among women on HAART. Our large prospective cohort study adds significant weight to the side of the balance of clinical research supporting the positive impact of HAART on the natural history of human papillomavirus-related cervical disease in HIV-infected women.
    AIDS (London, England) 05/2012; 26(13):1645-52. · 4.91 Impact Factor
  • Article: Community-based targeted case finding for tuberculosis and HIV in household contacts of patients with tuberculosis in South Africa.
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    ABSTRACT: South Africa has a high prevalence of tuberculosis (TB) and HIV-coinfected adults in whom TB is often diagnosed late in the course of disease. Improved case-finding approaches for TB and HIV are needed to reduce mortality and prevent transmission. We identified newly diagnosed index TB cases in a rural district and enrolled their households in a TB-HIV contact-tracing study. A group of randomly selected control households were enrolled to determine community prevalence of undetected TB and HIV. Field teams screened participants for TB symptoms, collected sputum specimens for smear microscopy and culture, provided HIV counseling and testing, and collected blood for CD4 testing. Participants were referred to public clinics for TB treatment and antiretroviral therapy. We evaluated 2,843 household contacts of 727 index patients with TB and 983 randomly selected control household members. The prevalence of TB in household contacts was 6,075 per 100,000 (95% confidence interval, 5,789-6,360 per 100,000), whereas the prevalence detected in randomly selected households was 407 per 100,000 (95% confidence interval, 0-912 per 100,000; prevalence difference, 5,668 per 100,000; P < 0.001). TB detected among contacts was less likely to be smear-positive than in the index patients (6% vs. 22%; P < 0.001). Most contacts with culture-confirmed TB were asymptomatic. At least one case of undiagnosed TB was found in 141 (19%) of 727 contact versus 4 (1%) of 312 control households. HIV testing was positive in 166 (11%) of 1,568 contacts tested versus 76 (14%) of 521 control participants tested (odds ratio, 1.48; P = 0.02). Active case finding in TB contact households should be considered to improve TB and HIV case detection in high-prevalence settings, but sensitive diagnostic tools are necessary.
    American Journal of Respiratory and Critical Care Medicine 03/2012; 185(10):1110-6. · 11.08 Impact Factor
  • Article: Designing family-centered male circumcision services: a conjoint analysis approach.
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    ABSTRACT: Male circumcision (MC) has become an important weapon in the fight against HIV/AIDS in many Sub-Saharan African countries. The successful implementation of a national MC program requires the design of circumcision services that are attractive to young men of various ages. For many potential clients, mothers and/or fathers will play an important role in the decision to be circumcised, and hence services will need to be designed with the preferences of mothers, fathers, and sons in mind. Our objective was to value multiple design characteristics of potential community-based MC services from the perspectives of mothers, fathers, and sons in Johannesburg, South Africa, and to test for concordance between their values for the design characteristics. Potential design characteristics of MC services were identified through open-ended interviews with key informants (n = 25). Preferences were estimated using conjoint analysis implemented as part of a cluster randomized household survey. Each participant was randomized to receive one of two possible blocks of conjoint analysis, each consisting of six forced-choice tasks comparing two possible MC services varying on 11 design characteristics. With only two levels for each attribute, our experimental design utilized a main effects orthogonal array. Data were analyzed using linear probability models, with tests of concordance of values using Wald tests generated from stratified estimates calculated using restricted least square estimation. A racially and geographically diverse sample consisting of 204 fathers, 204 mothers, and 237 sons completed the survey. In aggregate, requiring a follow-up visit was the most valued design factor (p < 0.001), followed by having a lower infection rate (p < 0.001), having less pain (p = 0.001), and a private waiting room (p = 0.001). Based on stratified analysis, sons also valued having the risks and benefits of MC explained (p = 0.01) and mothers valued requiring an HIV test as part of the procedure. Requiring an HIV test was the most significant difference between the respondents (p = 0.03), with sons finding it somewhat repulsive (p = 0.30). Our findings suggest that valuation of aspects of MC clinic design can diverge by decision maker. To better ensure utilization of services, these variations should be taken into account to prior to implementation of a national strategy in South Africa.
    The patient 01/2012; 5(2):101-11. · 0.57 Impact Factor
  • Article: Causes of death on antiretroviral therapy: a post-mortem study from South Africa.
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    ABSTRACT: Mortality in the first months of antiretroviral therapy (ART) is a significant clinical problem in sub-Saharan Africa. To date, no post-mortem study has investigated the causes of mortality in these patients. HIV-positive adults who died as in-patients at a Johannesburg academic hospital underwent chart-review and ultrasound-guided needle autopsy for histological and microbiological examination of lung, liver, spleen, kidney, bone marrow, lymph node, skin and cerebrospinal fluid. A clinico-pathologic committee considered all available data and adjudicated immediate and contributing causes of death. Thirty-nine adults were enrolled: 14 pre-ART, 15 early-ART (7-90 days), and 10 late-ART (>90 days). Needle sampling yielded adequate specimen in 100% of kidney, skin, heart and cerebrospinal fluid samples, 97% of livers and lungs, 92% of bone marrows, 87% of spleens and 68% of lymph nodes. Mycobacterial infections were implicated in 69% of deaths (26 of 27 of these due to M. tuberculosis), bacterial infections in 33%, fungal infections in 21%, neoplasm in 26%, and non-infectious organ failure in 26%. Immune reconstitution inflammatory syndrome (IRIS) was implicated in 73% of early-ART deaths. Post-mortem investigations revealed previously undiagnosed causes of death in 49% of cases. Multiple pathologies were common with 62% of subjects with mycobacterial infection also having at least one other infectious or neoplastic cause of death. Needle biopsy was efficient and yielded excellent pathology. The large majority of deaths in all three groups were caused by M. tuberculosis suggesting an urgent need for improved diagnosis and expedited treatment prior to and throughout the course of antiretroviral therapy. Complex, unrecognized co-morbidities pose an additional challenge.
    PLoS ONE 01/2012; 7(10):e47542. · 4.09 Impact Factor
  • Article: Short-course Combivir after single-dose nevirapine reduces but does not eliminate the emergence of nevirapine resistance in women.
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    ABSTRACT: In the Treatment Options Preservation Study (TOPS) trial, 4 or 7 days of Combivir (CBV; zidovudine/lamivudine) with maternal single-dose nevirapine (sdNVP) significantly reduced the emergence of NVP resistance as determined by virus population genotyping. To detect NVP resistance with greater sensitivity, we analysed TOPS samples by allele-specific real-time PCR (ASP). In a random subset of women from each arm of the trial, plasma samples from before and 6 weeks after sdNVP were analysed using ASP at codons 103, 181, 184 and 190. Samples were analysed from 27 women in the sdNVP arm and 24 each in the CBV 4-day (sdNVP/CBV4) and 7-day (sdNVP/CBV7) arms. ASP detected NVP-resistant variants in week 6 samples from 70% of women in the sdNVP arm, 29% in the sdNVP/CBV4 arm and 33% in sdNVP/CBV7 arm (P<0.01 for sdNVP/CBV4 or sdNVP/CBV7 versus sdNVP; P=1.0 for sdNVP/CBV4 versus sdNVP/CBV7). Lamivudine resistance was detected by ASP in only 1 of 51 women who received CBV. Short-course CBV significantly reduced but did not eliminate the emergence of NVP resistance after sdNVP. NVP-resistant variants were detected in about one-third of women despite CBV treatment, but the duration of persistence and clinical impact of these variants in response to antiretroviral therapy is uncertain.
    Antiviral therapy 11/2011; 17(2):327-36. · 3.16 Impact Factor
  • Article: Antiretroviral therapy refusal among newly diagnosed HIV-infected adults.
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    ABSTRACT: To determine rates and predictors of treatment refusal in newly identified HIV-infected individuals in Soweto, South Africa. It is designed as a cross-sectional study. We analyzed data from adult clients (>18 years) presenting for voluntary counseling and testing (VCT) at the Zazi Testing Center, Perinatal HIV Research Unit to determine rates of antiretroviral therapy (ART) refusal among treatment-eligible, HIV-infected individuals (CD4(+) cell count < 200 cells/μl or WHO stage 4). Multiple logistic regression models were used to investigate factors associated with refusal. From December 2008 to December 2009, 7287 adult clients were HIV tested after counseling. Two thousand, five hundred and sixty-two (35%) were HIV-infected, of whom 743 (29%) were eligible for immediate ART. One hundred and forty-eight (20%) refused referral to initiate ART, most of whom (92%) continued to refuse after 2 months of counseling. The leading reason for ART refusal was given as 'feeling healthy' (37%), despite clients having a median CD4(+) cell count of 110 cells/μl and triple the rate of active tuberculosis as seen in nonrefusers. In adjusted models, single clients [adjusted odds ratio (AOR) 1.80, 95% confidence interval (CI) 1.06-3.06] and those with active tuberculosis (AOR 3.50, 95% CI 1.55-6.61) were more likely to refuse ART. Nearly one in five treatment-eligible HIV-infected individuals in Soweto refused to initiate ART after VCT, putting them at higher risk for early mortality. 'Feeling healthy' was given as the most common reason to refuse ART, despite a suppressed CD4(+) count and comorbidities such as tuberculosis. These findings highlight the urgent need for research to inform interventions targeting ART refusers.
    AIDS (London, England) 08/2011; 25(17):2177-81. · 4.91 Impact Factor
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    Article: New regimens to prevent tuberculosis in adults with HIV infection.
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    ABSTRACT: Treatment of latent tuberculosis in patients infected with the human immunodeficiency virus (HIV) is efficacious, but few patients around the world receive such treatment. We evaluated three new regimens for latent tuberculosis that may be more potent and durable than standard isoniazid treatment. We randomly assigned South African adults with HIV infection and a positive tuberculin skin test who were not taking antiretroviral therapy to receive rifapentine (900 mg) plus isoniazid (900 mg) weekly for 12 weeks, rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks, isoniazid (300 mg) daily for up to 6 years (continuous isoniazid), or isoniazid (300 mg) daily for 6 months (control group). The primary end point was tuberculosis-free survival. The 1148 patients had a median age of 30 years and a median CD4 cell count of 484 per cubic millimeter. Incidence rates of active tuberculosis or death were 3.1 per 100 person-years in the rifapentine-isoniazid group, 2.9 per 100 person-years in the rifampin-isoniazid group, and 2.7 per 100 person-years in the continuous-isoniazid group, as compared with 3.6 per 100 person-years in the control group (P>0.05 for all comparisons). Serious adverse reactions were more common in the continuous-isoniazid group (18.4 per 100 person-years) than in the other treatment groups (8.7 to 15.4 per 100 person-years). Two of 58 isolates of Mycobacterium tuberculosis (3.4%) were found to have multidrug resistance. On the basis of the expected rates of tuberculosis in this population of HIV-infected adults, all secondary prophylactic regimens were effective. Neither a 3-month course of intermittent rifapentine or rifampin with isoniazid nor continuous isoniazid was superior to 6 months of isoniazid. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00057122.).
    New England Journal of Medicine 07/2011; 365(1):11-20. · 53.30 Impact Factor
  • Article: Epidemiology of tuberculosis and HIV: recent advances in understanding and responses.
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    ABSTRACT: Although tuberculosis (TB) continues to cause enormous suffering and overwhelm health care systems in areas with high HIV prevalence, there have been a number of recent significant advances in knowledge regarding the epidemiology, management, and control of HIV-related TB. TB remains the most common serious opportunistic infection in people with HIV infection and the leading cause of death. However, there is some reason for optimism. First, two trials addressing when to start antiretroviral therapy (ART) in HIV-infected adults with newly diagnosed TB have shown that earlier initiation of ART reduces mortality significantly. Second, there is trial evidence of efficacy in giving long-term isoniazid preventive treatment (IPT) to HIV-infected adults in high HIV-prevalence settings where TB reinfection is frequent (much like cotrimoxazole). Third, the search for an inexpensive, rapid, sensitive, and specific TB diagnostic that is able to replace smear and delayed mycobacterial culture has yielded promising results. Responding to massive TB epidemics in high HIV-prevalence settings, the World Health Organization has supplemented its directly observed treatment short-course strategy with one called the 3I's to actively screen and diagnose TB cases (intensified case finding), prevent new cases of TB with IPT, and prevent transmission of TB in congregate settings such as hospitals and clinics (infection control). Combating TB in high HIV-prevalence settings requires rapid and massive implementation of the 3I's with initiation of antiretrovirals and more effective efforts to prevent new HIV infections.
    Proceedings of the American Thoracic Society 06/2011; 8(3):288-93.
  • Article: The impact of highly active antiretroviral therapy on activities of daily living in HIV-infected adults in South Africa.
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    ABSTRACT: This study investigated the relationship between highly active antiretroviral therapy (HAART) and instrumental activities of daily living (IADLs) among two clinical cohorts in South Africa. Between 2003 and 2008 structured questionnaires were administered to HIV-positive patients attending outpatient clinics at an urban hospital (Soweto, n = 3,081) and a rural hospital (Acornhoek, n = 1,247). Among those receiving help, an average of 4.8 and 5.1 h of assistance with IADLs daily was reported (rural and urban participants, respectively), with the patient's mother and children assisting the most. Participants on HAART were 17 and 41% less likely to receive assistance with IADLs in the rural and urban cohorts, respectively, after adjusting for demographic characteristics, healthcare utilization, and CD4 counts. HAART significantly decreased the IADL assistance among patients in South Africa. Alongside clinical benefits, HAART has the potential to reduce the burden of HIV-related care, potentially extending wider social and economic gains to other family members.
    AIDS and Behavior 05/2011; 15(4):823-31. · 3.49 Impact Factor
  • Article: Survival in XDR TB: shifting the curve and shifting the paradigm.
    Neil A Martinson, Richard E Chaisson
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2011; 57(2):89-91. · 4.43 Impact Factor
  • Article: Sexual risk behaviors among HIV-infected South African men and women with their partners in a primary care program: implications for couples-based prevention.
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    ABSTRACT: We studied 1163 sexually-active HIV-infected South African men and women in an urban primary care program to understand patterns of sexual behaviors and whether these behaviors differed by partner HIV status. Overall, 40% reported a HIV-positive partner and 60% a HIV-negative or status unknown partner; and 17.5% reported >2 sex acts in the last 2 weeks, 16.4% unprotected sex in the last 6 months, and 3.7% >1 sex partner in the last 6 months. Antiretroviral therapy (ART) was consistently associated with decreased sexual risk behaviors, as well as with reporting a HIV-negative or status unknown partner. The odds of sexual risk behaviors differed by sex; and were generally higher among participants reporting a HIV-positive partner, but continued among those with a HIV-negative or status unknown partner. These data support ART as a means of HIV prevention. Engaging in sexual risk behaviors primarily with HIV-positive partners was not widely practiced in this setting, emphasizing the need for couples-based prevention.
    AIDS and Behavior 04/2011; 16(1):139-50. · 3.49 Impact Factor
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    Article: Active tuberculosis case-finding among pregnant women presenting to antenatal clinics in Soweto, South Africa.
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    ABSTRACT: Human immunodeficiency virus (HIV) and tuberculosis (TB) are among the leading causes of death among women of reproductive age worldwide. TB is a significant cause of maternal morbidity. Detection of TB during pregnancy could provide substantial benefits to women and their children. This was a cross-sectional implementation research study of integrating active TB case-finding into existing antenatal and prevention of mother-to-child transmission services in six clinics in Soweto, South Africa. All pregnant women 18 years of age or older presenting for routine care to these public clinics were screened for symptoms of active TB, cough for 2 weeks or longer, sputum production, fevers, night sweats, or weight loss, regardless of their HIV status. Participants with any symptom of active TB were asked to provide a sputum specimen for smear microscopy, mycobacterial culture and drug-susceptibility testing. Between December 2008 and July 2009, 3963 pregnant women were enrolled and screened for TB, of whom 1454 (36.7%) were HIV-seropositive. Any symptom of TB was reported by 23.1% of HIV-seropositive and 13.8% of HIV-seronegative women (P < 0.01). Active pulmonary TB was diagnosed in 10 of 1454 HIV-seropositve women (688 per 100,000) and 5 of 2483 HIV-seronegative women (201 per 100,000, P = 0.03). The median CD4⁺ T-cell count among HIV-seropositive women with TB was similar to that of HIV-seropositive women without TB (352 versus 333 cells/μL, P = 0.85). There is a high burden of active TB among HIV-seropositive pregnant women. TB screening and provision of isoniazid preventive therapy and antiretroviral therapy should be integrated with prevention of mother-to-child transmission services.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2011; 57(4):e77-84. · 4.43 Impact Factor
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    Article: Longitudinal analysis of QuantiFERON-TB Gold In-Tube in children with adult household tuberculosis contact in South Africa: a prospective cohort study.
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    ABSTRACT: QuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions. Prospective study with six month longitudinal follow-up. Among 270 enrolled pediatric contacts, 196 (73%) underwent 6-month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24-35]) to 38% (103/270, 95% CI [32-44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23-34]) to 33% (88/263, 95%CI [21-32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1-72]) and baseline TST positivity ≥5 mm (AOR 5.2 95%CI [1.2-23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1-321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001-0.24]). Among pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates.
    PLoS ONE 01/2011; 6(10):e26787. · 4.09 Impact Factor
  • Article: The Clinical Impact and Cost-Effectiveness of Routine, Voluntary HIV Screening in South Africa
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    ABSTRACT: Background: Although 900,000 HIV-infected South Africans receive antiretroviral therapy, the majority of South Africans with HIV remain undiagnosed. Methods: We use a published simulation model of HIV case detection and treatment to examine 3 HIV screening scenarios, in addition to current practice as follows: (1) one-time; (2) every 5 years; and (3) annually. South African model input data include the following: 16.9% HIV prevalence, 1.3% annual incidence, 49% test acceptance rate, HIV testing costs of $6.49/patient, and a 47% linkage-to-care rate (including 2 sequential antiretroviral therapy regimens) for identified cases. Outcomes include life expectancy, direct medical costs, and incremental cost-effectiveness. Results: HIV screening one-time, every 5 years, and annually increase HIV-infected quality-adjusted life expectancy (mean age 33 years) from 180.6 months (current practice) to 184.9, 187.6, and 197.2 months. The incremental cost-effectiveness of one-time screening is dominated by screening every 5 years. Screening every 5 years and annually each have incremental cost-effectiveness ratios of $1570/quality-adjusted life year and $1720/quality-adjusted life year. Screening annually is very cost-effective even in settings with the lowest incidence/prevalence, with test acceptance and linkage rates both as low as 20%, or when accounting for a stigma impact at least four-fold that of the base case. Conclusions: In South Africa, annual voluntary HIV screening offers substantial clinical benefit and is very cost-effective, even with highly constrained access to care and treatment.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2010; 56(1):26-35. · 4.43 Impact Factor
  • Article: Decreased sexual risk behavior in the era of HAART among HIV-infected urban and rural South Africans attending primary care clinics.
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    ABSTRACT: In light of increasing access to HAART in sub-Saharan Africa, we conducted a longitudinal study to assess the impact of HAART on sexual risk behaviors among HIV-infected South Africans in urban and rural primary care clinics. Prospective observational cohort. We conducted a cohort study at rural and urban primary care HIV clinics in South Africa consisting of 1544 men and 4719 women enrolled from 2003 to 2010, representing 19703 clinic visits. The primary outcomes were being sexually active, unprotected sex, and more than one sex partner and were evaluated at 6 monthly intervals. Generalized estimated equations assessed the impact of HAART on sexual risk behaviors. Among 6263 HIV-infected men and women, over a third (37.2%) initiated HAART during study follow-up. In comparison to pre-HAART follow-up, visits while receiving HAART were associated with a decrease in those reporting being sexually active [adjusted odds ratio: 0.86 (95% confidence interval: 0.78-0.95)]. Unprotected sex and having more than one sex partner were reduced at visits following HAART initiation compared to pre-HAART visits [adjusted odds ratio: 0.40 (95% confidence interval: 0.34-0.46) and adjusted odds ratio: 0.20 (95% confidence interval: 0.14-0.29), respectively]. Sexual risk behavior significantly decreased following HAART initiation among HIV-infected South African men and women in primary care programs. The further expansion of antiretroviral treatment programs could enhance HIV prevention efforts in Africa.
    AIDS (London, England) 11/2010; 24(17):2687-96. · 4.91 Impact Factor
  • Article: Patient referral from nurses to doctors in a nurse-led HIV primary care clinic in South Africa: implications for training and support.
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    ABSTRACT: Health services in sub-Saharan Africa are under great pressure to provide adequate clinical care due to the continued HIV epidemic, and nurse-driven models of care are one means to address physician shortages. This case-control study examines the reasons for and correlates of patient referral from nurses to physicians at HIV primary care clinics in South Africa prior to initiating antiretroviral treatment. Ninety-seven HIV-infected cases who required physician consolation and 160 controls who did not require physician consultation (matched on gender, age, and date of clinic visit) were consecutively enrolled at both an urban and rural HIV primary care clinic during a 12-month period beginning in March 2006. Univariate and multivariate logistic regression models were used to assess correlates of patient referral to a physician. Cases were more likely to have lower CD4 cell counts and have WHO Stages III and IV disease compared to controls (p<0.05). Predictors of patient referral were a CD4 cell count between 50 and 200 cells/µl (adj OR: 5.27, 95% CI: 2.16-12.88, p<0.0001), a CD4 cell count below 50 cells/µl (adj OR: 3.47, 95% CI: 1.12-10.78, p=0.032), and Stage IV disease (adj OR: 4.58, 95% CI: 1.35-15.60, p=0.015). Additionally, the following ICD-10 clinical diagnoses were associated with patient referral: tuberculosis, aplastic and other anemias, and lower respiratory tract infection (p<0.05). Nurses can provide adequate clinical and diagnostic management for certain clinical conditions to HIV-infected patients. Further studies are needed to examine specifically how HIV healthcare delivery can be scaled-up in resource-limited settings with a high burden of HIV, but with a minimal healthcare infrastructure.
    AIDS Care 11/2010; 22(11):1332-9. · 1.60 Impact Factor
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    Article: Progression and regression of premalignant cervical lesions in HIV-infected women from Soweto: a prospective cohort.
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    ABSTRACT: To ascertain progression and regression of cervical dysplasia in HIV-infected women in Soweto. Prospective cohort. Women attending an HIV wellness clinic were offered cervical smears as part of care; smears were assessed using the Bethesda system. Those with high-grade lesions or worse were referred for colposcopy. Progression analyses included women with at least two smears at least 5.5 months apart. Hazard ratios were used to ascertain predictors of progression. Two thousand, three hundred and twenty-five women had a baseline smear; their median age and CD4 cell count was 32 years and 312 cells/μl, respectively; 17% were taking highly active antiretroviral therapy (HAART); 62, 20 and 14% had normal, low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL), respectively. Of those with baseline normal or LSIL smears, 1074 had another smear; progression from normal to LSIL was 9.6/100 person-years (95% CI 8.3-11.1) and progression from normal or LSIL to HSIL was 4.6/100 person-years (95% CI 3.9-5.5). Of 225 women with LSIL at baseline and at least one subsequent smear at least 11.5 months later, 44.0% regressed to normal (21.2/100 person-years (95% CI 17.5-25.7)). Multivariate models suggested increasing risk for progression in women with CD4 cell count below 500 cells/μl and HAART may reduce the risk of progression [adjusted hazard ratio (aHR) 0.72 (0.52-0.99)]. HIV-infected women have high rates of prevalent and incident HSIL and LSIL with relatively low risk of regression to normal from LSIL. HAART appears to protect against progression. Our findings suggest cervical screening intervals should be less than 10 years - irrespective of age in women with CD4 cell counts below 500 cells/μl.
    AIDS (London, England) 11/2010; 25(1):87-94. · 4.91 Impact Factor

Institutions

  • 2006–2013
    • University of the Witwatersrand
      • • Anatomical Pathology Division
      • • Perinatal HIV Research Unit
      • • School of Public Health
      Johannesburg, Gauteng, South Africa
  • 2010–2012
    • Johns Hopkins Bloomberg School of Public Health
      Baltimore, MD, USA
  • 2007–2012
    • Johns Hopkins University
      • Center for Tuberculosis Research
      Baltimore, MD, USA
  • 2011
    • University of Rochester
      • Department of Community and Preventive Medicine
      Rochester, NY, USA
  • 2010–2011
    • Brown University
      • Alpert Medical School
      Providence, RI, USA
  • 2008
    • Chris Hani Baragwanath Hospital
      Johannesburg, Gauteng, South Africa