Kennedy Otwombe | University of the Witwatersrand (original) (raw)

Papers by Kennedy Otwombe

Research paper thumbnail of Multiple levels of influence in predicting sexual activity and condom use among adolescents in Soweto, Johannesburg, South Africa

Journal of HIV/AIDS & social services, 2013

ABSTRACT HIV prevalence amongst 15–19 year olds in South Africa is 6.7% and 2.5% in females and m... more ABSTRACT HIV prevalence amongst 15–19 year olds in South Africa is 6.7% and 2.5% in females and males respectively. Using an interviewer-administered cross-sectional survey, we examined individual, interpersonal, family and community factors associated with sexual activity and condom use among 506 adolescents 16–18 years from Soweto, Johannesburg. The sample was mainly female (59%, n = 298). Using multivariate logistic regression, males (OR:2.6, CI: 1.4–4.8), older partners (OR:4.5, CI: 1.5–13.8), hazardous alcohol use (OR:2.4, CI: 1.1–5.2) and permissive attitudes about sex (OR:1.6, CI: 1.3–2.1) predicted sexual activity. A first partner at a younger age (OR:1.2, CI: 1.1–1.4) and having older partners (OR:0.29, CI: 0.13–0.68) predicted lack of condom use. For females, increasing age (OR:2.7 CI:1.4–5.5), older partners (OR: 3.3 CI:1.4–7.6), and permissive attitudes about sex (OR: 1.6 CI:1.2–2.1) predicted sexual activity. Multiple levels have to be addressed in developing HIV prevention programs for adolescents in Soweto.

Research paper thumbnail of Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses

PloS one, 2014

Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, cond... more Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 3...

Research paper thumbnail of Table of contents

Research paper thumbnail of Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial

Interim results from the children with HIV early antiretroviral (CHER) trial showed that early an... more Interim results from the children with HIV early antiretroviral (CHER) trial showed that early antiretroviral therapy (ART) was life-saving for infants infected with HIV. In view of the few treatment options and the potential toxicity associated with lifelong ART, in the CHER trial we compared early time-limited ART with deferred ART. CHER was an open-label randomised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher. 377 infants were randomly allocated to one of three groups: deferred ART (ART-Def), immediate ART for 40 weeks (ART-40W), or immediate ART for 96 weeks (ART-96W), with subsequent treatment interruption. The randomisation schedule was stratified by clinical site with permuted blocks of random sizes to balance the numbers of infants allocated to each group. Criteria for ART initiation in the ART-Def group and re-initiation after interruption in the other groups were CD4% less than 25% in infancy; otherwise, the criteria were CD4% less than 20% or Centers for Disease Control and Prevention severe stage B or stage C disease. Combination therapy of lopinavir-ritonavir, zidovudine, and lamivudine was the first-line treatment regimen at ART initiation and re-initiation. The primary endpoint was time to failure of first-line ART (immunological, clinical, or virological) or death. Comparisons were done by intention-to-treat analysis, with use of time-to-event methods. This trial is registered with ClinicalTrials.gov, number NCT00102960. 377 infants were enrolled, with a median age of 7·4 weeks, CD4% of 35%, and HIV RNA log 5·7 copies per mL. Median follow-up was 4·8 years; 34 infants (9%) were lost to follow-up. Median time to ART initiation in the ART-Def group was 20 weeks (IQR 16-25). Time to restarting of ART after interruption was 33 weeks (26-45) in ART-40W and 70 weeks (35-109) in ART-96W; at the end of the trial, 19% of patients in ART-40W and 32% of patients in ART-96W remained off ART. Proportions of follow-up time spent on ART were 81% in the ART-Def group, 70% in the ART-40W group, and 69% in the ART-96W group. 48 (38%) of 125 children in the ART-Def group, 32 (25%) of 126 in the ART-40W group, and 26 (21%) of 126 in the ART-96W group reached the primary endpoint. The hazard ratio, relative to ART-Def, was 0·59 (95% CI 0·38-0·93, p=0·02) for ART-40W and 0·47 (0·27-0·76, p=0·002) for ART-96W. Three children in ART-Def, three in ART-40W, and one in ART-96W switched to second-line ART. Early time-limited ART had better clinical and immunological outcomes than deferred ART, with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption, with marginally better outcomes. US National Institutes of Health.

Research paper thumbnail of Uptake of Genital Mucosal Sampling in HVTN 097, a Phase 1b HIV Vaccine Trial in South Africa

PLoS ONE, 2014

Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune resp... more Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p,0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies.

Research paper thumbnail of Health-seeking behaviours by gender among adolescents in Soweto, South Africa

Global Health Action, 2015

Background: Adolescents are an important age-group for preventing disease and supporting health y... more Background: Adolescents are an important age-group for preventing disease and supporting health yet little is known about their health-seeking behaviours. Objective: We describe socio-demographic characteristics and health-seeking behaviours of adolescents in Soweto, South Africa, in order to broaden our understanding of their health needs. Design: The Botsha Bophelo Adolescent Health Study was an interviewer-administered cross-sectional survey of 830 adolescents (14Á19 years) conducted in Soweto from 2010 to 2012. Health-seeking behaviours were defined as accessing medical services and/or being hospitalised in the 6 months prior to the survey. Chi-square analysis tested for associations between gender, other socio-demographic and behavioural characteristics, and health-seeking behaviours. Results: Of 830 adolescents, 57% were female, 50% were aged 17Á19 years, 85% were enrolled in school, and 78% reported experiencing medium or high food insecurity. Males were more likely than females to report sexual debut (64% vs. 49%; p B0.0001) and illicit drug use (11% vs. 3%; p B0.0001). Approximately 27% (n0224) and 8% (n 065) reported seeking healthcare or being hospitalised respectively in the previous 6 months, with no significant differences by gender. Services were most commonly sought at medical clinics (75%), predominantly because of flu-like symptoms (32%), followed by concerns about HIV (10%). Compared to females, males were more likely to seek healthcare for condom breakage (8% vs. 2%; p 00.02). Relative to males, a significantly higher proportion of females desired general healthcare services (85% vs. 78%; p00.0091), counselling (82% vs. 70%; p B0.0001), and reproductive health services (64% vs. 56%; p 00.02). Conclusions: A quarter of male and female adolescents accessed health services in the 6 months prior to the interview. Adolescents reported a gap between the availability and the need for general, reproductive, and counselling services. Integrated adolescent-friendly, school-based health services are recommended to bridge this gap.

Research paper thumbnail of Early severe HIV disease precedes early antiretroviral therapy in infants: Are we too late?

Journal of the International AIDS Society, 2014

Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral... more Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral therapy (ART) by three months of age in a programmatic setting in South Africa. Design: This was a programmatic cohort study. Methods: Electronic and manual data extraction from databases and antiretroviral registers in 20 public clinics in Cape Town and electronic data extraction from a large ART service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of all infants initiated on ART by three months of age between June 2007 and September 2010 were extracted. Demographics, immunological and clinical stage at ART initiation were analyzed descriptively by chi-square, two-sample t-test and KaplanÁ Meier methods.

Research paper thumbnail of Kganya Motsha Adolescent Centre: a model for adolescent friendly HIV management and reproductive health for adolescents in Soweto, South Africa

AIDS Care, 2015

This paper reports on Kganya Motsha Adolescent Centre, an adolescent program specifically establi... more This paper reports on Kganya Motsha Adolescent Centre, an adolescent program specifically established to provide voluntary counseling and testing as well as management of HIV-positive young people in Soweto, South Africa. A retrospective cross-sectional analysis, using clinic records of young people accessing services from 2008 to 2012, was conducted. Of the 11,522 who tested, 7689 (67%) were females. The total number of HIV infections was 410, with an HIV prevalence of 3.6% (95% CI 3.2-3.9%). More females (332, 4% vs. 72, 2%; p < 0.0001) were HIV-infected than males. Of those testing HIV positive, 109 (26.5%) had a median CD4 cell count of 491 (IQR 345-686) cells/mm 3 . Only 12/410 individuals (2.9%) were eligible for antiretroviral treatment and 10 (2.4%) of those successfully received treatment. The program observed that young people testing HIV positive would not return for follow up blood specimens or confirmatory results. Future programs should consider innovative ways of retaining adolescents in care to reduce potential HIV transmissions that could lead to deteriorating health.

Research paper thumbnail of A Review of the Study Designs and Statistical Methods Used in the Determination of Predictors of All-Cause Mortality in HIV-Infected Cohorts: 2002–2011

PLoS ONE, 2014

Background: Research in the predictors of all-cause mortality in HIV-infected people has widely b... more Background: Research in the predictors of all-cause mortality in HIV-infected people has widely been reported in literature. Making an informed decision requires understanding the methods used.

Research paper thumbnail of The Effect of a Maturing Antiretroviral Program on Early Mortality for Patients with Advanced Immune-Suppression in Soweto, South Africa

PLoS ONE, 2013

We hypothesize that time to initiate care and maturity of a treatment program impact on outcome o... more We hypothesize that time to initiate care and maturity of a treatment program impact on outcome of severely immuno-compromised patients with higher risk of mortality. We conducted a retrospective cohort analysis at the Perinatal HIV Research Unit Adult ART clinic, Soweto, South Africa. ELIGIBILITY CRITERIA FOR THIS ANALYSIS WERE: attendance for minimum one visit between August 2004 and August 2010, age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;18 years, CD4 count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 cells/mm(3) and ART-naïve at screening. We followed participants up to one year after ART initiation. We defined years 2004-2007 and 2008-2010 as the early and late eras respectively. Chi-square test and survival analysis methods were used for mortality comparisons between eras. Of 2357 patients eligible for antiretroviral treatment, 395 (17%) had CD4 counts &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 cells/mm(3) and ART-naïve at screening. Overall 261 (66%) were women. Patients had similar median age (35 vs. 33.5 years, p=0.08), time to HAART initiation (7 days, p=0.18) and baseline CD4 count (20 vs. 23 cells/mm(3), p=0.5) between eras. Overall 63 (16%) patients died in their first year of treatment (2 per 100 person-months) and the main cause of death was tuberculosis (n=23, 37%). The proportion of deaths (52/262 vs. 11/133, p=0.003) and time to death from enrolment (logrank p=0.04) were significantly different between eras. Mortality decreased as the ART program matured in Soweto while time to initiation of treatment remained similar in both eras. Because ART guidelines were consistent during both eras, it is possible that with time, management of patients improved as expertise was gained.

Research paper thumbnail of CD4 Counts and Viral Loads of Newly Diagnosed HIV-Infected Individuals: Implications for Treatment as Prevention

PLoS ONE, 2014

To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-tes... more To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-testers, not immediately eligible for treatment initiation by current South Africa treatment guidelines. This was a cross-sectional study in a high-volume, free-of-charge HIV testing centre in Soweto, South Africa. We enrolled first time HIV testers and collected demographic and risk-behaviour data and measured CD4 count and viral load. Between March and October 2011, a total of 4793 adults attended VCT and 1062 (22%) tested positive. Of the 1062, 799 (75%) were ART naïve and 348/799 (44%) were first-time HIV testers. Of this group of 348, 225 (65%) were female. Overall their median age, CD4 count and viral load was 34 years (IQR: 28-41), 364 (IQR: 238-542) cells/mm3 and 13,000 (IQR: 2050-98171) copies/ml, respectively. Female first time HIV testers had higher CD4 counts (419 IQR: 262-582 vs. 303 IQR: 199-418 cells/mm3) and lower viral loads (9,100 vs. 34,000 copies/ml) compared to males. Of 183 participants with CD4 count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;350 cells/mm3, 62 (34%) had viral loads &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10,000 copies/ml. A large proportion of HIV infected adults not qualifying for immediate ART at the CD4 count threshold of 350 cells/mm3 have high viral loads. HIV-infected men at their first HIV diagnosis are more likely to have lower CD4 counts and higher viral loads than women.

Research paper thumbnail of Predictors of parent–adolescent communication in post-apartheid South Africa: A protective factor in adolescent sexual and reproductive health

Journal of Adolescence, 2014

Research paper thumbnail of Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial

Tropical Medicine & …, 2005

Objective To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antise... more Objective To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children. ... Setting and participants A total of 427 children with chronic suppurative otitis media enrolled from 141 schools ...

Research paper thumbnail of Does routine prophylactic oral flucloxacillin reduce the incidence of post-circumcision infections?

American Journal of Infection Control, 2013

Background: Cost-effective and safe practices are required for the scale-up of medical male circu... more Background: Cost-effective and safe practices are required for the scale-up of medical male circumcision (MMC), a strategy recommended for biomedical HIV prevention. Methods: A retrospective medical record review was conducted of post-circumcision wound infection incidence at a massive MMC program in Soweto, South Africa. We compared patients who received routine 250 mg prophylactic flucloxacillin 4 times daily orally for 5 days with those who did not receive prophylaxis. Patients with HIV infection and those with missing prophylaxis data were excluded from the analysis. Collated data included prophylaxis received, age, return for follow-up, and presence and grading of wound infection at follow-up. Results: In total, 1,291 patients were eligible: 646 flucloxacillin recipients and 645 non-recipients. Median age of flucloxacillin recipients was 24 years (interquartile range 20-29 years) and for nonrecipients it was 23 years (interquartile range 16-28 years). Eighty-one percent of flucloxacillin recipients and 87% of nonrecipients (P ¼ .0019) returned for follow-up. Wound infection was present in 0.7% (5 of 646) of flucloxacillin recipients and 1.2% (8 of 645) of non-recipients (P ¼ .4). Use of routine prophylactic flucloxacillin did not significantly reduce incidence of post-MMC wound infection (odds ratio, 0.6; 95% confidence interval, 0-1.2). Conclusions: When compared with no prophylactic flucloxacillin, routine prophylactic flucloxacillin does not significantly reduce the risk of post-MMC wound infection in a massive circumcision program.

Research paper thumbnail of Effect of in-utero HIV exposure and antiretroviral treatment strategies on measles susceptibility and immunogenicity of measles vaccine

AIDS, 2013

The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We ev... more The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We evaluated the effect of in-utero HIV-exposure and antiretroviral treatment (ART) strategies on measles antibody kinetics prior and following measles vaccination. Infants aged 6-12 weeks were enrolled. This included HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU). Additionally, we enrolled perinatal HIV-infected infants with CD4% equal or greater than 25% randomized to deferred-ART until clinically or immunologically indicated (Group-3) or immediate-ART initiation (Group-4). Group-4 was further randomized to interrupt ART at 1 year (Group-4a) or 2 years of age (Group-4b). Additionally, a convenience sample of HIV-infected infants with CD4⁺ less than 25% initiated on immediate-ART was enrolled (Group-5). Measles immunoglobulin-G antibodies were quantified by an indirect enzyme immunoassay with titers 330 mIU/ml or more considered &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;sero-protective&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. The referent group was HUU-children. The proportion with sero-protective titers at 7.3 weeks of age was higher in HUU (65.2%) compared with any HIV-infected group (range: 16.7-41.8%), but dropped to less than 17% in all groups at age 19.6 weeks. Twenty-eight weeks following the first measles vaccine, Group-4a was less likely to have sero-protective titers (79.3%) as compared to HUU (91.1%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), Group-3 (95.7%; P=0.003) or Group-4b (92.1%; P=0.018). Although the proportion with sero-protective levels were similar between groups immediately postbooster dose, this was lower in HEU (79.6%; P=0.002) and Group-4a (80.3%; P=0.010) compared with HUU (94.3%) 41-weeks later. Greater waning of immunity among HIV-infected children in whom ART was interrupted and in HEU following a booster-dose, indicate the possible need for further measles-booster doses after 2 years of age in these children.

Research paper thumbnail of Sharing perspectives and experiences of doctoral fellows in the first cohort of Consortium for Advanced Research Training in Africa: 2011–2014

Global Health Action, 2014

Background: Resolution of public health problems in Africa remains a challenge because of insuffi... more Background: Resolution of public health problems in Africa remains a challenge because of insufficient skilled human resource capacity. The Consortium for Advanced Research Training in Africa (CARTA) was established to enhance capacity in multi-disciplinary health research that will make a positive impact on population health in Africa. Objective: The first cohort of the CARTA program describes their perspectives and experiences during the 4 years of fellowship and puts forward suggestions for future progress and direction of research in Africa. Conclusions: The model of training as shown by the CARTA program is an effective model of research capacity building in African academic institutions. An expansion of the program is therefore warranted to reach out to more African academics in search of advanced research training.

Research paper thumbnail of Multiple levels of influence in predicting sexual activity and condom use among adolescents in Soweto, Johannesburg, South Africa

Journal of HIV/AIDS & social services, 2013

ABSTRACT HIV prevalence amongst 15–19 year olds in South Africa is 6.7% and 2.5% in females and m... more ABSTRACT HIV prevalence amongst 15–19 year olds in South Africa is 6.7% and 2.5% in females and males respectively. Using an interviewer-administered cross-sectional survey, we examined individual, interpersonal, family and community factors associated with sexual activity and condom use among 506 adolescents 16–18 years from Soweto, Johannesburg. The sample was mainly female (59%, n = 298). Using multivariate logistic regression, males (OR:2.6, CI: 1.4–4.8), older partners (OR:4.5, CI: 1.5–13.8), hazardous alcohol use (OR:2.4, CI: 1.1–5.2) and permissive attitudes about sex (OR:1.6, CI: 1.3–2.1) predicted sexual activity. A first partner at a younger age (OR:1.2, CI: 1.1–1.4) and having older partners (OR:0.29, CI: 0.13–0.68) predicted lack of condom use. For females, increasing age (OR:2.7 CI:1.4–5.5), older partners (OR: 3.3 CI:1.4–7.6), and permissive attitudes about sex (OR: 1.6 CI:1.2–2.1) predicted sexual activity. Multiple levels have to be addressed in developing HIV prevention programs for adolescents in Soweto.

Research paper thumbnail of Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine induced immune responses

PloS one, 2014

Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, cond... more Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 3...

Research paper thumbnail of Table of contents

Research paper thumbnail of Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial

Interim results from the children with HIV early antiretroviral (CHER) trial showed that early an... more Interim results from the children with HIV early antiretroviral (CHER) trial showed that early antiretroviral therapy (ART) was life-saving for infants infected with HIV. In view of the few treatment options and the potential toxicity associated with lifelong ART, in the CHER trial we compared early time-limited ART with deferred ART. CHER was an open-label randomised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher. 377 infants were randomly allocated to one of three groups: deferred ART (ART-Def), immediate ART for 40 weeks (ART-40W), or immediate ART for 96 weeks (ART-96W), with subsequent treatment interruption. The randomisation schedule was stratified by clinical site with permuted blocks of random sizes to balance the numbers of infants allocated to each group. Criteria for ART initiation in the ART-Def group and re-initiation after interruption in the other groups were CD4% less than 25% in infancy; otherwise, the criteria were CD4% less than 20% or Centers for Disease Control and Prevention severe stage B or stage C disease. Combination therapy of lopinavir-ritonavir, zidovudine, and lamivudine was the first-line treatment regimen at ART initiation and re-initiation. The primary endpoint was time to failure of first-line ART (immunological, clinical, or virological) or death. Comparisons were done by intention-to-treat analysis, with use of time-to-event methods. This trial is registered with ClinicalTrials.gov, number NCT00102960. 377 infants were enrolled, with a median age of 7·4 weeks, CD4% of 35%, and HIV RNA log 5·7 copies per mL. Median follow-up was 4·8 years; 34 infants (9%) were lost to follow-up. Median time to ART initiation in the ART-Def group was 20 weeks (IQR 16-25). Time to restarting of ART after interruption was 33 weeks (26-45) in ART-40W and 70 weeks (35-109) in ART-96W; at the end of the trial, 19% of patients in ART-40W and 32% of patients in ART-96W remained off ART. Proportions of follow-up time spent on ART were 81% in the ART-Def group, 70% in the ART-40W group, and 69% in the ART-96W group. 48 (38%) of 125 children in the ART-Def group, 32 (25%) of 126 in the ART-40W group, and 26 (21%) of 126 in the ART-96W group reached the primary endpoint. The hazard ratio, relative to ART-Def, was 0·59 (95% CI 0·38-0·93, p=0·02) for ART-40W and 0·47 (0·27-0·76, p=0·002) for ART-96W. Three children in ART-Def, three in ART-40W, and one in ART-96W switched to second-line ART. Early time-limited ART had better clinical and immunological outcomes than deferred ART, with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption, with marginally better outcomes. US National Institutes of Health.

Research paper thumbnail of Uptake of Genital Mucosal Sampling in HVTN 097, a Phase 1b HIV Vaccine Trial in South Africa

PLoS ONE, 2014

Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune resp... more Because sexual transmission of HIV occurs across mucosal membranes, understanding the immune responses of the genital mucosa to vaccines may contribute knowledge to finding an effective candidate HIV vaccine. We describe the uptake of rectal secretion, cervical secretion and seminal mucosal secretion sampling amongst volunteers in a Phase 1b HIV vaccine trial. Age at screening, gender, study site and the designation of the person conducting the informed consent procedure were collected for volunteers who screened for the HVTN 097 study. A total of 211 volunteers (54% female) were screened at three sites in South Africa: Soweto (n = 70, 33%), Cape Town (n = 68, 32%) and Klerksdorp (n = 73, 35%). Overall uptake of optional mucosal sampling amongst trial volunteers was 71% (n = 149). Compared to Cape Town, volunteers from Soweto and Klerksdorp were less likely to consent to sampling (Soweto OR 0.08 CI: 0.03-0.25 p,0.001 and Klerksdorp OR 0.13 CI: 0.04-0.41 p = 0.001). In contrast, volunteers over 25 years of age were 2.39 times more likely to consent than younger volunteers (CI: 1.13-5.08, p = 0.02). Further studies are required to better understand the cultural, demographic and sociobehavioral factors which influence willingness to participate in mucosal sampling in HIV prevention studies.

Research paper thumbnail of Health-seeking behaviours by gender among adolescents in Soweto, South Africa

Global Health Action, 2015

Background: Adolescents are an important age-group for preventing disease and supporting health y... more Background: Adolescents are an important age-group for preventing disease and supporting health yet little is known about their health-seeking behaviours. Objective: We describe socio-demographic characteristics and health-seeking behaviours of adolescents in Soweto, South Africa, in order to broaden our understanding of their health needs. Design: The Botsha Bophelo Adolescent Health Study was an interviewer-administered cross-sectional survey of 830 adolescents (14Á19 years) conducted in Soweto from 2010 to 2012. Health-seeking behaviours were defined as accessing medical services and/or being hospitalised in the 6 months prior to the survey. Chi-square analysis tested for associations between gender, other socio-demographic and behavioural characteristics, and health-seeking behaviours. Results: Of 830 adolescents, 57% were female, 50% were aged 17Á19 years, 85% were enrolled in school, and 78% reported experiencing medium or high food insecurity. Males were more likely than females to report sexual debut (64% vs. 49%; p B0.0001) and illicit drug use (11% vs. 3%; p B0.0001). Approximately 27% (n0224) and 8% (n 065) reported seeking healthcare or being hospitalised respectively in the previous 6 months, with no significant differences by gender. Services were most commonly sought at medical clinics (75%), predominantly because of flu-like symptoms (32%), followed by concerns about HIV (10%). Compared to females, males were more likely to seek healthcare for condom breakage (8% vs. 2%; p 00.02). Relative to males, a significantly higher proportion of females desired general healthcare services (85% vs. 78%; p00.0091), counselling (82% vs. 70%; p B0.0001), and reproductive health services (64% vs. 56%; p 00.02). Conclusions: A quarter of male and female adolescents accessed health services in the 6 months prior to the interview. Adolescents reported a gap between the availability and the need for general, reproductive, and counselling services. Integrated adolescent-friendly, school-based health services are recommended to bridge this gap.

Research paper thumbnail of Early severe HIV disease precedes early antiretroviral therapy in infants: Are we too late?

Journal of the International AIDS Society, 2014

Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral... more Objective: To describe the degree of HIV disease progression in infants initiating antiretroviral therapy (ART) by three months of age in a programmatic setting in South Africa. Design: This was a programmatic cohort study. Methods: Electronic and manual data extraction from databases and antiretroviral registers in 20 public clinics in Cape Town and electronic data extraction from a large ART service at Chris Hani Baragwanath Hospital in Soweto were performed. Records of all infants initiated on ART by three months of age between June 2007 and September 2010 were extracted. Demographics, immunological and clinical stage at ART initiation were analyzed descriptively by chi-square, two-sample t-test and KaplanÁ Meier methods.

Research paper thumbnail of Kganya Motsha Adolescent Centre: a model for adolescent friendly HIV management and reproductive health for adolescents in Soweto, South Africa

AIDS Care, 2015

This paper reports on Kganya Motsha Adolescent Centre, an adolescent program specifically establi... more This paper reports on Kganya Motsha Adolescent Centre, an adolescent program specifically established to provide voluntary counseling and testing as well as management of HIV-positive young people in Soweto, South Africa. A retrospective cross-sectional analysis, using clinic records of young people accessing services from 2008 to 2012, was conducted. Of the 11,522 who tested, 7689 (67%) were females. The total number of HIV infections was 410, with an HIV prevalence of 3.6% (95% CI 3.2-3.9%). More females (332, 4% vs. 72, 2%; p < 0.0001) were HIV-infected than males. Of those testing HIV positive, 109 (26.5%) had a median CD4 cell count of 491 (IQR 345-686) cells/mm 3 . Only 12/410 individuals (2.9%) were eligible for antiretroviral treatment and 10 (2.4%) of those successfully received treatment. The program observed that young people testing HIV positive would not return for follow up blood specimens or confirmatory results. Future programs should consider innovative ways of retaining adolescents in care to reduce potential HIV transmissions that could lead to deteriorating health.

Research paper thumbnail of A Review of the Study Designs and Statistical Methods Used in the Determination of Predictors of All-Cause Mortality in HIV-Infected Cohorts: 2002–2011

PLoS ONE, 2014

Background: Research in the predictors of all-cause mortality in HIV-infected people has widely b... more Background: Research in the predictors of all-cause mortality in HIV-infected people has widely been reported in literature. Making an informed decision requires understanding the methods used.

Research paper thumbnail of The Effect of a Maturing Antiretroviral Program on Early Mortality for Patients with Advanced Immune-Suppression in Soweto, South Africa

PLoS ONE, 2013

We hypothesize that time to initiate care and maturity of a treatment program impact on outcome o... more We hypothesize that time to initiate care and maturity of a treatment program impact on outcome of severely immuno-compromised patients with higher risk of mortality. We conducted a retrospective cohort analysis at the Perinatal HIV Research Unit Adult ART clinic, Soweto, South Africa. ELIGIBILITY CRITERIA FOR THIS ANALYSIS WERE: attendance for minimum one visit between August 2004 and August 2010, age &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;18 years, CD4 count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 cells/mm(3) and ART-naïve at screening. We followed participants up to one year after ART initiation. We defined years 2004-2007 and 2008-2010 as the early and late eras respectively. Chi-square test and survival analysis methods were used for mortality comparisons between eras. Of 2357 patients eligible for antiretroviral treatment, 395 (17%) had CD4 counts &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 50 cells/mm(3) and ART-naïve at screening. Overall 261 (66%) were women. Patients had similar median age (35 vs. 33.5 years, p=0.08), time to HAART initiation (7 days, p=0.18) and baseline CD4 count (20 vs. 23 cells/mm(3), p=0.5) between eras. Overall 63 (16%) patients died in their first year of treatment (2 per 100 person-months) and the main cause of death was tuberculosis (n=23, 37%). The proportion of deaths (52/262 vs. 11/133, p=0.003) and time to death from enrolment (logrank p=0.04) were significantly different between eras. Mortality decreased as the ART program matured in Soweto while time to initiation of treatment remained similar in both eras. Because ART guidelines were consistent during both eras, it is possible that with time, management of patients improved as expertise was gained.

Research paper thumbnail of CD4 Counts and Viral Loads of Newly Diagnosed HIV-Infected Individuals: Implications for Treatment as Prevention

PLoS ONE, 2014

To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-tes... more To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-testers, not immediately eligible for treatment initiation by current South Africa treatment guidelines. This was a cross-sectional study in a high-volume, free-of-charge HIV testing centre in Soweto, South Africa. We enrolled first time HIV testers and collected demographic and risk-behaviour data and measured CD4 count and viral load. Between March and October 2011, a total of 4793 adults attended VCT and 1062 (22%) tested positive. Of the 1062, 799 (75%) were ART naïve and 348/799 (44%) were first-time HIV testers. Of this group of 348, 225 (65%) were female. Overall their median age, CD4 count and viral load was 34 years (IQR: 28-41), 364 (IQR: 238-542) cells/mm3 and 13,000 (IQR: 2050-98171) copies/ml, respectively. Female first time HIV testers had higher CD4 counts (419 IQR: 262-582 vs. 303 IQR: 199-418 cells/mm3) and lower viral loads (9,100 vs. 34,000 copies/ml) compared to males. Of 183 participants with CD4 count &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;350 cells/mm3, 62 (34%) had viral loads &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 10,000 copies/ml. A large proportion of HIV infected adults not qualifying for immediate ART at the CD4 count threshold of 350 cells/mm3 have high viral loads. HIV-infected men at their first HIV diagnosis are more likely to have lower CD4 counts and higher viral loads than women.

Research paper thumbnail of Predictors of parent–adolescent communication in post-apartheid South Africa: A protective factor in adolescent sexual and reproductive health

Journal of Adolescence, 2014

Research paper thumbnail of Topical quinolone vs. antiseptic for treating chronic suppurative otitis media: a randomized controlled trial

Tropical Medicine & …, 2005

Objective To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antise... more Objective To compare a topical quinolone antibiotic (ciprofloxacin) with a cheaper topical antiseptic (boric acid) for treating chronic suppurative otitis media in children. ... Setting and participants A total of 427 children with chronic suppurative otitis media enrolled from 141 schools ...

Research paper thumbnail of Does routine prophylactic oral flucloxacillin reduce the incidence of post-circumcision infections?

American Journal of Infection Control, 2013

Background: Cost-effective and safe practices are required for the scale-up of medical male circu... more Background: Cost-effective and safe practices are required for the scale-up of medical male circumcision (MMC), a strategy recommended for biomedical HIV prevention. Methods: A retrospective medical record review was conducted of post-circumcision wound infection incidence at a massive MMC program in Soweto, South Africa. We compared patients who received routine 250 mg prophylactic flucloxacillin 4 times daily orally for 5 days with those who did not receive prophylaxis. Patients with HIV infection and those with missing prophylaxis data were excluded from the analysis. Collated data included prophylaxis received, age, return for follow-up, and presence and grading of wound infection at follow-up. Results: In total, 1,291 patients were eligible: 646 flucloxacillin recipients and 645 non-recipients. Median age of flucloxacillin recipients was 24 years (interquartile range 20-29 years) and for nonrecipients it was 23 years (interquartile range 16-28 years). Eighty-one percent of flucloxacillin recipients and 87% of nonrecipients (P ¼ .0019) returned for follow-up. Wound infection was present in 0.7% (5 of 646) of flucloxacillin recipients and 1.2% (8 of 645) of non-recipients (P ¼ .4). Use of routine prophylactic flucloxacillin did not significantly reduce incidence of post-MMC wound infection (odds ratio, 0.6; 95% confidence interval, 0-1.2). Conclusions: When compared with no prophylactic flucloxacillin, routine prophylactic flucloxacillin does not significantly reduce the risk of post-MMC wound infection in a massive circumcision program.

Research paper thumbnail of Effect of in-utero HIV exposure and antiretroviral treatment strategies on measles susceptibility and immunogenicity of measles vaccine

AIDS, 2013

The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We ev... more The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We evaluated the effect of in-utero HIV-exposure and antiretroviral treatment (ART) strategies on measles antibody kinetics prior and following measles vaccination. Infants aged 6-12 weeks were enrolled. This included HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU). Additionally, we enrolled perinatal HIV-infected infants with CD4% equal or greater than 25% randomized to deferred-ART until clinically or immunologically indicated (Group-3) or immediate-ART initiation (Group-4). Group-4 was further randomized to interrupt ART at 1 year (Group-4a) or 2 years of age (Group-4b). Additionally, a convenience sample of HIV-infected infants with CD4⁺ less than 25% initiated on immediate-ART was enrolled (Group-5). Measles immunoglobulin-G antibodies were quantified by an indirect enzyme immunoassay with titers 330 mIU/ml or more considered &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;sero-protective&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. The referent group was HUU-children. The proportion with sero-protective titers at 7.3 weeks of age was higher in HUU (65.2%) compared with any HIV-infected group (range: 16.7-41.8%), but dropped to less than 17% in all groups at age 19.6 weeks. Twenty-eight weeks following the first measles vaccine, Group-4a was less likely to have sero-protective titers (79.3%) as compared to HUU (91.1%; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001), Group-3 (95.7%; P=0.003) or Group-4b (92.1%; P=0.018). Although the proportion with sero-protective levels were similar between groups immediately postbooster dose, this was lower in HEU (79.6%; P=0.002) and Group-4a (80.3%; P=0.010) compared with HUU (94.3%) 41-weeks later. Greater waning of immunity among HIV-infected children in whom ART was interrupted and in HEU following a booster-dose, indicate the possible need for further measles-booster doses after 2 years of age in these children.

Research paper thumbnail of Sharing perspectives and experiences of doctoral fellows in the first cohort of Consortium for Advanced Research Training in Africa: 2011–2014

Global Health Action, 2014

Background: Resolution of public health problems in Africa remains a challenge because of insuffi... more Background: Resolution of public health problems in Africa remains a challenge because of insufficient skilled human resource capacity. The Consortium for Advanced Research Training in Africa (CARTA) was established to enhance capacity in multi-disciplinary health research that will make a positive impact on population health in Africa. Objective: The first cohort of the CARTA program describes their perspectives and experiences during the 4 years of fellowship and puts forward suggestions for future progress and direction of research in Africa. Conclusions: The model of training as shown by the CARTA program is an effective model of research capacity building in African academic institutions. An expansion of the program is therefore warranted to reach out to more African academics in search of advanced research training.