Publications (25)47.5 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV- participants from Brazil (n = 240), India (n = 480), Malawi (n = 481), Peru (n = 239), South Africa (480), Thailand (n = 240), and Zimbabwe (n = 240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p < 0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.
- [Show abstract] [Hide abstract] ABSTRACT: Background: South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa. Methods: Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing. Results: VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition. Conclusions: Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression.
- [Show abstract] [Hide abstract] ABSTRACT: We assessed treatment outcomes on third-line in a public-sector treatment program. Retrospective study of patients on third-line ART at Themba Lethu Clinic in Johannesburg, South Africa. Follow-up time accrued until the earliest of death, loss to follow-up or close of dataset. Of the 57 patients initiating third-line after second-line failure, 39 (68%) initiated ART at Themba Lethu while 18 (32%) were referral patients. Of those on third-line, 49% (n=28) were male with a median age of 39.8 years (IQR 35.6-45.7). At 6 and 12 months after initiation of first-line ART only 55% (18/33) and 69% (25/36) on third-line suppressed their viral load (<400copies/ml). Third-line patients showed lower rates of viral suppression at 6 and 12 months after switching to second-line compared to those who switched to second-line and are still on it (33% vs. 82% and 60% vs. 85%, respectively). Median CD4 count and VL at start of third-line was 222cells/mm3 (IQR 122-359) and 4.3 log10 (IQR 2.6-4.9), respectively. Third-line, patients were followed for a median of 0.8 years (IQR 0.4-1.0). The proportion that suppressed their VL at 3 and 6 months after third-line initiation was 60% and 86%, respectively. By the end of the study period only one patient had died, two were lost and 6 had transferred out. Poor long-term response to first- and/or second-line therapy due to less than perfect adherence or drug resistance development may increase the risk for treatment failure and the need or third-line ART. Larger studies with longer follow up are needed.
- [Show abstract] [Hide abstract] ABSTRACT: Introduction Cervical cancer is the most common cancer among women in Sub-Saharan Africa. Cervical cancer is treatable if detected timeously, yet only 20% of South African women have ever been for a Pap smear in their lifetime due to limited access to screening, transport or child care responsibilities. Objective To evaluate the acceptability of self-collection for cervical cancer screening. We aimed to identify which self-collection device women prefer and if they would consider using them for routine cervical cancer screening. Methods HIV-positive women (>18 years) from urban and rural HIV clinics were interviewed following an education session on HIV, human papillomavirus (HPV) and cervical cancer. Participants were shown three self-collection devices; (i) an Evalyn cervical brush, (ii) a Delphilavager and (iii) a tampon-like plastic wand before completing a short questionnaire. Results A total of 106 women from the urban (n = 52) and rural (n = 54) clinic were interviewed. Overall 51% of women preferred the cervical brush, while fewer women preferred the tampon-like plastic wand (31%) or lavage sampler (18%). More than 75% of women from the rural site preferred the cervical brush, compared to 22% from the urban site (p < 0.001). Women from the urban clinic preferred the tampon-like plastic wand (45%) and then the lavage sampler (33%), as compared to women from the rural clinic (19% and 4%, respectively). Conclusion Women from urban or rural settings had different preferences for the various self-collection devices. Patient self-collection with HPV testing may be an acceptable way to improve coverage to cervical cancer screening in high risk HIV-seropositive women.
Dataset: File S1
- [Show abstract] [Hide abstract] ABSTRACT: Little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART) in sub-Saharan Africa. We examined the effect of incident pregnancy after HAART initiation on clinical response to HAART. We evaluated a prospective clinical cohort of adult women initiating HAART in Johannesburg, South Africa between 1 April 2004 and 31 March 2011, and followed up until an event, transfer, drop-out, or administrative end of follow-up on 30 September 2011. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study. Main exposure was having experienced pregnancy after HAART initiation; main outcome was death and (separately) death or new AIDS event. We calculated adjusted hazard ratios (HRs) and 95% confidence limits (CL) using marginal structural Cox proportional hazards models. The study included 7,534 women, and 20,813 person-years of follow-up; 918 women had at least one recognized pregnancy during follow-up. For death alone, the weighted (adjusted) HR was 0.84 (95% CL 0.44, 1.60). Sensitivity analyses confirmed main results, and results were similar for analysis of death or new AIDS event. Incident pregnancy was associated with a substantially reduced hazard of drop-out (HR = 0.62, 95% CL 0.51, 0.75). Recognized incident pregnancy after HAART initiation was not associated with increases in hazard of clinical events, but was associated with a decreased hazard of drop-out. High rates of pregnancy after initiation of HAART may point to a need to better integrate family planning services into clinical care for HIV-infected women.
- [Show abstract] [Hide abstract] ABSTRACT: Background: There is little evidence comparing treatment outcomes between adolescents and other age groups particularly in resource limited settings. Methods: Retrospective analysis of data from 7 HIV clinics across urban Gauteng (n=5) and rural Mpumalanga (n=2), South Africa. The analysis compared HIV-positive ART-naive young adolescents (10-14years), older adolescents (15-19) and young adults (20-24years) to adults (≥24years) initiated onto standard first-line antiretroviral therapy (ART) between April 2004-August 2010. Log-binomial regression was used to estimate relative risk (RR) of failure to suppress viral load (≥400copies/ml) or failure to achieve an adequate CD4 response at 6 or 12months. The effect of age group on virological failure, mortality and loss to follow-up (LTFU;≥90d since scheduled visit date) was estimated using Cox proportional hazards models. Results: Of 42,427 patients initiating ART, 310(0.7%) were young adolescents, 342(0.8%) were older adolescents and 1599(3.8%) were young adults. Adolescents were similar to adults in terms of proportion male, baseline CD4 count, hemoglobin and TB. Compared to adults, both older adolescents (6months RR 1.75 95% CI 1.25-2.47) and young adults (6months RR 1.33 95% CI 1.10-1.60 and 12months RR 1.64 95% CI 1.23-2.19) were more likely to have an unsuppressed viral load and were more likely to fail virologically (HR 2.90 95% CI 1.74-4.86; HR 2.94 95% CI 1.63-5.31). There was no difference in risk of mortality by age category, compared to adults. Young adolescents were less likely to be LTFU at any time period after ART initiation (HR 0.43 95% CI 0.26-0.69) whereas older adolescents and young adults were more likely to be LTFU after ART initiation (HR 1.38 95% CI 1.07-1.78; HR 1.52 95% CI 1.34-1.72) compared to adults. Conclusion: HIV-infected adolescents and young adults between 15-24years have poorer ART treatment outcomes. Interventions are needed to help improve outcomes and retention in care in this unique population.
- [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVE:: Recent studies have raised concerns about a change in rates of pregnancy among HIV-negative women exposed to tenofovir.Here, our objective was todetermine among HIV-positive women whether use of tenofovir at HAART initiation or thereafter is associated with subsequent changes in incidence of pregnancy. DESIGN:: Analysis of prospectively collected clinical data. METHODS:: We used Cox proportional hazards models and logistic regression to estimate hazard ratios and odds-ratios for the association of baseline tenofovir use and time to first incident pregnancy. We used marginal structural Cox models to estimate hazard ratios for the association of current tenofovir use and time to first incident pregnancy. RESULTS:: We studied 7,275 women, of whom 1,199 were initiated on tenofovir-based HAART regimens, and who experienced a total of 894 pregnancies in 17,200 person-years of follow-up. Analyses showed slight reductions in hazards of pregnancy among women who used tenofovir, but without sufficient precision to draw strong conclusions. Sensitivity analyses confirmed main results. CONCLUSIONS:: Tenofovir may be associated with a lower hazard or rate of pregnancy in women receiving HAART. However, conclusions are limited by low precision, the observational nature of the data, and possible uncontrolled confounding by temporal trends in contraception use and other factors.
- [Show abstract] [Hide abstract] ABSTRACT: Peripheral neuropathy (PN) is associated with advanced HIV disease and may be a complication of antiretroviral therapy (ART) or anti-tuberculosis (TB) drugs, specifically isoniazid (INH). The effect of non-ART-drug-related PN on treatment outcomes is yet to be determined. We analysed prospectively collected cohort data for HIV-infected ART-naive adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa from June 2004 to June 2009. Patients who presented with signs and symptoms of numbness or dysesthesia prior to initiation of ART were defined as having PN. Cox proportional hazard models were used to estimate the effect of PN alone (HIV-related PN) or PN with a history of INH use (TB-related PN) on mortality, lost to follow-up (LTFU), persistent and recurrent PN by 12 months of follow-up. Of the 9,399 patients initiating ART, 3.9 % had HIV-related PN while a further 1.8 % had TB-related PN. Patients with PN did not have a significantly higher risk of mortality compared to those without PN (hazard ratio (HR) 1.17 95 % CI 0.92-1.49). Patients with TB-related PN were less likely to be LTFU by 12 months (HR 0.65 95 % CI 0.44-0.97) compared to those without PN. Patients with HIV-related PN were at increased risk of persistent PN at 3 months post-ART initiation. Patients with HIV-related PN had a similar risk of recurrent PN compared to those with TB-related PN (HR 1.28 95 % CI 0.72-2.27). We demonstrate that patients with PN at initiation of ART present with advanced HIV disease. Completion of TB treatment may reduce the risk of persistent PN in patients with TB-related PN. Use of HIV drugs, even neurotoxic ones, may overall limit neuropathy.
- [Show abstract] [Hide abstract] ABSTRACT: Pregnancy is a common indication for initiation of highly active antiretroviral therapy (HAART) in sub-Saharan Africa. Our objective was to evaluate how pregnancy at treatment initiation predicts virologic response to HAART. We evaluated an open cohort of 9173 patients who initiated HAART between April 2004 and September 2009 in the Themba Lethu Clinic in Johannesburg, South Africa. Risk ratios were estimated using log-binomial regression; hazard ratios were estimated using Cox proportional hazards models; time ratios were estimated using accelerated failure time models. We controlled for calendar date, age, ethnicity, employment status, history of smoking, tuberculosis, WHO stage, weight, body mass index, hemoglobin, CD4 count and CD4 percent, and whether clinical care was free. Extensive sensitivity and secondary analyses were performed. During follow-up, 822 nonpregnant women and 70 pregnant women experienced virologic failure. In adjusted analyses, pregnancy at baseline was associated with reduced risk of virologic failure by 6 months [risk ratio 0.66, 95% confidence limits (CL): 0.35 to 1.22] and with reduced hazard of virologic failure over follow-up (hazard ratio: 0.69, 95% CL: 0.50 to 0.95). The adjusted time ratio for failure was 1.44 (95% CL: 1.13 to 1.84), indicating 44% longer time to event among women pregnant at baseline. Sensitivity analyses generally confirmed main findings. Pregnancy at HAART initiation is not associated with increased risk of virologic failure at 6 months or during longer follow-up.
- [Show abstract] [Hide abstract] ABSTRACT: Hepatitis B virus (HBV) infection with undetectable hepatitis B surface antigen (HBsAg) has been reported in HIV patients, but the clinical significance is unknown. This study presents the prevalence of HBV DNA in HIV-positive patients negative for all HBV serological markers and a retrospective evaluation of the clinical course of mono- and co-infection. Of 502 HIV-positive patients, 222 tested negative for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc). An in-house real-time PCR targeting the HBV S-region was used to quantify HBV DNA. HBV isolates were genotyped. Baseline demographic and clinical characteristics of HBV DNA-positive and HBV DNA-negative patients were described. Treatment outcomes of patients at 6, 12, and 24 months after initiation of antiretroviral therapy (ART) were summarized. HBV DNA was detected in 5.4% (12/222) of serologically negative patients. Mean HBV viral load was 5359.2 IU/ml (standard deviation (SD) ±12 768.27). Eleven HBV isolates belonged to genotype A and one to genotype C. There were no significant differences in baseline characteristics or clinical course between the HBV DNA-positive and HBV DNA-negative groups. We found 5.4% of the HBV serologically-negative HIV-positive patients had low levels of HBV DNA. There were no significant differences in clinical outcome between the mono- and co-infected groups.
- [Show abstract] [Hide abstract] ABSTRACT: Many resource limited settings (RLS) suffer from high rates of both cervical cancer and HIV. Limited HPV serology data are available from RLS; such data could help describe local patterns of HPV infection and predict vaccine efficacy. To determine seropositivity to HPV types 6, 11, 16 and 18 in HIV-infected women from South Africa (SA), Botswana and Brazil. HPV serotyping for high-risk types 6, 11, 16 and 18 was performed on samples collected from HIV-infected women from 2003-2010 using competitive Luminex Immuno Assay (HPV-4cLIA). We examined the association between seropositivity to these HPV types and country of enrollment, CD4, HIV-1 RNA level, and Pap smear. HPV serology results were available for 487 HIV-infected women (157, 170 and 160 from SA, Botswana and Brazil respectively). Approximately 65% of women had serum antibodies to one of the 4 HPV types and less than 3% of women had antibodies all 4 serotypes. Approximately 30% women demonstrated antibodies to type 16 HPV. Rates of seropositivity to HPV 11, and HPV 16+18 varied significantly between countries. Statistical difference was also shown in women in different age categories in the different countries. There was no difference in serology results compared by CD4 count, HIV viral load or Pap smear results. These data suggest that the quadrivalent vaccine may be effective in preventing HPV infection in these countries.
- [Show abstract] [Hide abstract] ABSTRACT: Little is known about how the prevalence and incidence of neurological disease in HIV-infected patients in resource-limited settings. We present an analysis of neurological and neurocognitive function in antiretroviral naïve individuals in multinational resource-limited settings. This prospective multinational cohort study, a substudy of a large international randomized antiretroviral treatment trial, was conducted in seven low- and middle-income countries in sub-Saharan Africa, South America, and Asia. Subjects were HIV-infected and met regional criteria to initiate antiretroviral therapy. Standardized neurological examination and a brief motor-based neuropsychological examination were administered. A total of 860 subjects were studied. Overall 249 (29%) had one or more abnormalities on neurological examinations, but there was a low prevalence of HIV-associated dementia (HAD) and minor neurocognitive disorder (MND). Twenty percent of subjects had evidence of peripheral neuropathy. There were significant differences across countries (p < 0.001) in neuropsychological test performance. In this first multinational study of neurological function in antiretroviral naïve individuals in resource-limited settings, there was a substantial prevalence of peripheral neuropathy and low prevalence of dementia and other CNS diseases. There was significant variation in neurocognitive test performance and neurological examination findings across countries. These may reflect cultural differences, differences in HIV-related and unrelated diseases, and variations in test administration across sites. Longitudinal follow-up after antiretroviral treatment initiation may help to define more broadly the role of HIV in these differences as well as the impact of treatment on performance.
- [Show abstract] [Hide abstract] ABSTRACT: Background The prevalence of asymptomatic STIs and urethritis/cervicitis pathogen-associated patient characteristics were determined among patients attending a HIV treatment centre in Johannesburg. Methods Consenting consecutive HIV-infected patients, asymptomatic for symptoms/signs of genital discharge, were screened over 12 months for gonorrhoea, trichomoniasis, chlamydial and Mycoplasma genitalium infections using a real-time PCR assay. Bacterial vaginosis (BV) and Candida were detected by microscopy (women only). Serological assays diagnosed syphilis (RPR/TPPA) and herpes simplex type 2 (IgG ELISA) infections. Patients returned at 2 weeks; those with positive results were treated and given contact slips for partners. If available, patients' most recent CD4 (83%) and viral load (VL) (60%) results were recorded. Demographic, clinical and behavioural data were collected by nurse-administered questionnaire. A descriptive analysis was conducted to obtain frequency distributions of patient and STI prevalence data. Associations were investigated using the χ2 test at a 5% level of significance. A multiple logistic regression model was fitted to find factors associated with urethritis/cervicitis pathogens. Results 1109 patients were enrolled (551 men, 558 women). Compared with men, women were younger with a mean age [SD] of 35.0 [7.3] vs 37.9 [7.9] years (p<0.001), reported more STIs in the past year (65.5% vs 56.5%, p=0.002), were less likely to know their partner's HIV status (53.1% vs 62.3%, p=0.007), were more likely to be on HAART (70.4% vs 59.7%, p<0.001) with an undetectable VL (81.0% vs 69.9%, p<0.001) and a higher mean [SD] CD4 count of 346  vs 232  cells/mm3 (p<0.001). Urethritis/cervicitis pathogens were detected in 119/558 (21.3%) women and 90/550 (16.4%) men (p=0.035). BV and Candida were detected in 155 (28.0%) and 101 (18.3%) women, respectively. Detection of urethritis/cervicitis pathogens was associated with recent sexual intercourse with a regular partner (adjusted OR, aOR 1.64, 95% CI 1.08% to 2.48%). Trichomoniasis was associated with female gender (aOR 2.45, 95% CI 1.39% to 4.32%) and sub-optimal condom use with regular partners (aOR 2.04, 95% CI 1.23% to 3.41%). Conclusions Urethritis/cervicitis pathogens were highly prevalent among this asymptomatic population. The benefit of introducing such STI screening programmes to improve reproductive health and HIV prevention efforts requires further study.
- [Show abstract] [Hide abstract] ABSTRACT: Few data exist regarding the human papillomavirus (HPV) types in penile warts (PW) of HIV-infected men in Africa. Nurses collected penile swabs for HPV typing from 74 HIV-positive men with PW. HPV genotyping was performed using the Roche Linear Array Test. Analysis was performed on data relating to 74 samples. The mean age of the men was 36.0 years and 78.5% (51/65) were uncircumcised. Of the 73/74 validated results, all tested positive for HPV; 42.5% (31/73) and 32.9% (24/73) had HPV types 6 and 11, respectively. 84.9% of men tested positive for any oncogenic type: 20/73 (27.4%) were positive for type 16, 11/73 (15.1%) were positive for type 18 and 8/73 (11.0%) men had both types. Our study shows a high prevalence (68.5%) of HPV type 6 and/or 11 in this male population with PW. Given the poor availability of treatment, a quadrivalent vaccine for men may have significant benefit.
University of the Witwatersrand
Johannesburg, Gauteng, South Africa
- Department of Internal Medicine