Mhairi Maskew

University of the Witwatersrand, Johannesburg, Gauteng, South Africa

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Publications (58)204.96 Total impact

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    ABSTRACT: The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to preventing KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: The incidence of Kaposi's Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406-2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102-187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13-0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9-80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to preventing KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV. © 2014 Wiley Periodicals, Inc.
    International Journal of Cancer 04/2014; · 6.20 Impact Factor
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    ABSTRACT: In April 2010, South Africa replaced stavudine with tenofovir in first-line antiretroviral therapy (ART) despite tenofovir's higher cost. We examined treatment outcomes over 24 months amongst patients initiated on tenofovir-based vs. stavudine-based first-line regimens. Prospective cohort analysis of 3940 patients newly initiating either stavudine-based (April 2009 to March 2010) or tenofovir-based (April 2010 to March 2011) ART in Johannesburg, South Africa. Cox proportional hazards models and Fine and Gray's competing risk regression accounting for death were used to model mortality and loss to follow-up, respectively. Linear and log-binomial regression were used to evaluate associations with immunologic response and unsuppressed virus (≥400 copies/ml), respectively. About 1878 patients prescribed tenofovir and 2062 patients prescribed stavudine were included. One hundred and sixty-six (8.8%) tenofovir and 244 (11.8%) stavudine patients died. Three hundred and fifty (18.6%) tenofovir and 379 (18.4%) stavudine patients were lost to follow-up over 24 months on ART. Adjusted regression models showed tenofovir and stavudine were comparable regarding death, loss to follow-up, immunologic response and virologic status. We found no difference in mortality, loss to follow-up, immunological and virologic outcomes over the first 24-months on ART associated with tenofovir compared with stavudine.
    Tropical Medicine & International Health 03/2014; · 2.94 Impact Factor
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    ABSTRACT: Introduction: The prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear. Methods: This was a cohort study of HIV-positive adults initiating antiretroviral therapy (ART) between April 2004 and August 2007 who achieved viral suppression (<400 copies/ml) by six months on treatment in South Africa. Immunological response at six months was defined as: (1) absolute CD4 reached (<200 vs. ≥200 cells/ml); (2) absolute CD4 reached (0-49, 50-200 and ≥200 cells/ml); and (3) CD4 increase from ART initiation (<0, 0-49, 50-199 and ≥200 cells/ml). We used Cox regression models to determine the relationship between each definition and both new AIDS-defining condition and death. Results: A total of 4129 patients were eligible for analysis; 212 (5.1%) of those patients experienced a new AIDS-defining condition and 154 (3.7%) died. Smaller CD4 gains by six months were associated with higher hazards of progression to AIDS (CD4<50 vs. ≥200 cells/ml; adjusted hazard ratio (aHR): 2.6; 95% CI: 1.2-2.1) and death (aHR: 2.8; 95% CI: 1.4-5.7). A decrease in CD4 count since ART initiation through six months (aHR: 2.4; 95% CI: 1.2-4.9) and smaller CD4 count gains (0-49 cells/ml; aHR: 2.0; 95% CI: 1.2-3.4 and 50-199 cells/ml; aHR: 1.5; 95% CI: 0.9-2.2) were also associated with greater risk of progression to AIDS compared to an increase of ≥200 cells/ml. When we examined mortality differences by gender among this virally suppressed cohort, a higher proportion of males died compared to females, 4.7% versus 3.2%, p=0.01. However, in multivariable analysis, we did not observe any significant differences: aHR: 1.39; 95% CI: 0.98-1.95. Conclusions: Patients on ART with poor CD4 recovery early in treatment are at greater risk of progression to new AIDS diagnosis or death despite viral suppression. Approaches to managing this sub-group of patients need further investigation.
    Journal of the International AIDS Society 01/2014; 17(1):18651. · 3.94 Impact Factor
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    ABSTRACT: Objectives To describe the characteristics of HIV-infected patients experiencing herpes zoster after antiretroviral therapy (ART) initiation and to describe the incidence and predictors of a herpes zoster diagnosis. Methods Adult patients initiating ART from April 2004 to September 2011 at the Themba Lethu Clinic in Johannesburg, South Africa were included. Patients were followed from ART initiation until the date of first herpes zoster diagnosis, or death, transfer, loss to follow-up, or dataset closure. Herpes zoster is described using incidence rates (IR) and predictors of herpes zoster are presented as subdistribution hazard ratios (sHR) and 95% confidence intervals (95% CI). Results Fifteen thousand and twenty-five patients were included; 62% were female, the median age was 36.6 years, and the median baseline CD4 count was 98 cells/mm3. Three hundred and forty patients (2.3%) experienced herpes zoster in a median of 26.1 weeks after ART initiation. Most (76.7% [Au?1]) occurred within 1 year of initiation, for a 1-year IR of 18.1/1000 person-years. In an adjusted model, patients with low CD4 counts (<50 vs. ≥200 cells/mm3; sHR 1.71, 95% CI 1.21–2.47) and with a prior episode of herpes zoster (sHR 1.79, 95% CI 1.14–2.68) were at increased risk of incident herpes zoster. Conclusions While only 2% of patients were diagnosed with herpes zoster in this cohort, patients with low CD4 counts and those with prior episodes of herpes zoster were at higher risk for a herpes zoster diagnosis.
    International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 01/2014; · 2.17 Impact Factor
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    ABSTRACT: Challenges to HIV care in resource limited settings (RLS) include malnutrition. Limited evidence supports the benefit of nutritional supplementation when starting antiretroviral therapy (ART) in RLS. Randomized controlled pilot study. HIV-positive ART-naive adults with self-reported weight loss were randomized to receive ART plus FutureLife porridge(R) nutritional supplement (NS) (388 kcal/day) or ART alone (Controls) for 6 months. Patients returned for monthly assessments and blood was drawn at enrolment and 6 months on ART. Differences in body composition, biochemical and laboratory parameters were estimated at 6 months on treatment. Of the 36 randomized patients, 26 completed the 6 month follow-up (11 NS vs 15 Controls). At enrolment, groups were similar in terms of age, gender, body mass index (BMI) and bioelectrical impedance. NS patients had a lower median CD4 count (60 cells/mm3 [IQR 12--105 vs 107 cells/mm3 [IQR 63--165]; p = 0.149) and haemoglobin (10.3 g/dL [IQR 9.0-11.3] vs 13.1 g/dL [IQR 11.1-14.7]; p = 0.001).At 6 months, NS patients increased their median CD4 count by 151 cells/mm3 [IQR 120--174) vs 77 cells/mm3 [IQR 33--145] in the Controls. NS patients had higher mean percentage change in body weight (12.7% vs 4.9%; p = 0.047), BMI (7.8% vs 5.5%; p = 0.007), absolute CD4 count (83.0% vs 46.4%, p = 0.002) and hemoglobin (9.5% vs 1.0%; p = 0.026). Patients in the NS arm had a higher mean percentage fat-free mass (16.7% vs -3.5%, p = 0.036), total body water (13.0% vs -1.9%, p = 0.026), intracellular water (16.1% vs -4.1%, p = 0.010) and basal metabolic rate (5.3% vs -0.2%, p = 0.014) compared to Controls. Patients in the NS arm also showed an improvement in physical activity at 6 months post-ART initiation compared to Controls (p = 0.037). Preliminary results are encouraging and suggest that NS taken concurrently with ART can promote weight gain, improve immune response and improve physical activity in HIV-positive patients that present at ART initiation with weight loss.
    Nutrition Journal 08/2013; 12(1):111. · 2.65 Impact Factor
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    ABSTRACT: BACKGROUND:: The possible impact of co-infection with Kaposi's sarcoma associated herpes virus on the response to antiretroviral therapy (ART) is unknown. Prospective studies are rare, particularly in Africa. METHODS:: We enrolled a prospective cohort of HIV-infected adults initiating ART in Johannesburg, South Africa. Subjects were defined as seropositive to KSHV if reactive to either KSHV lytic K8.1 or latent Orf73 antigen or both. Subjects were followed from ART initiation until 18-months on treatment. HIV viral load and CD4 counts were tested 6 monthly. Linear generalized estimating and log-binomial regression models were used to estimate the effect of KSHV infection on immunologic recovery and response as well as HIV viral load suppression within 18-months after ART initiation. RESULTS:: 385 subjects initiating ART from November 2008-March 2009 were eligible including 184 (48%) KSHV+. The KSHV+ group was similar to the KSHV- in terms of age, gender, initiating CD4 count, body mass index, tuberculosis and haemoglobin levels. The KSHV+ group gained a similar number of cells at 6- (difference of 10cells/mm, 95%CI:-11-31), 12- (3cells/mm, 95%CI:-19-25) and 18-months (24cells/mm, 95%CI:-13-61) compared to the KSHV- group. Adjusted relative risk of failure to suppress viral load to <400 copies/mL (1.03; 95%CI:0.90-1.17) were similar for KSHV+ and KSHV- by 6-months on treatment. CONCLUSIONS:: In a population with a high KSHV prevalence, HIV-positive adults co-infected with KSHV achieved similar immunologic and virologic responses to ART early after treatment initiation compared to those KSHV-.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2013; · 4.65 Impact Factor
  • AIDS 02/2013; 27(4):645-650. · 6.41 Impact Factor
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    ABSTRACT: OBJECTIVE: To examine the interaction between CD4 cell count, viral load suppression and duration of antiretroviral therapy (ART) on mortality. METHODS: Cohort analysis of HIV-infected patients initiating ART between April 2004 and June 2011 at a large public sector clinic in Johannesburg, South Africa. A log-linear model with Poisson distribution was used to estimate risk of death as a function of the interaction between current CD4 count, current viral load suppression and duration on ART in 12-month intervals. We calculated predicted mortality using estimated coefficients within combinations of predictors. RESULTS: Amongst 14 932 ART patients, 1985 (13.3%) died. Current CD4 was the strongest predictor of death (<50 vs. ≥550 cells/mm(3) - RR: 46.3; 95% CI: 26.8-80), while unsuppressed current viral load vs. suppressed (RR: 1.8; 95% CI: 1.5-2.1) and short duration of ART (0-11.9 vs. 66-71.9 months RR: 1.7; 95% CI: 1.2-2.3) also predicted death. Our interaction model showed that mortality was highest in the first 12 months on treatment across all CD4 and viral load strata. As current CD4 and duration on ART increased and viral load suppression occurred, mortality dropped. CD4 count was the strongest predictor of death. The relative effect of current CD4 count varied strongly by viral load and duration of ART (from 1.3 to 55). Lack of suppression increased the risk of mortality upwards of six-fold depending on time on ART and current CD4. CONCLUSIONS: Our findings show that while CD4 count is the strongest predictor of death, the effect is modified by viral load and the duration of ART. Assessment of risk should take into account all three factors.
    Tropical Medicine & International Health 02/2013; · 2.94 Impact Factor
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    ABSTRACT: OBJECTIVE: HIV-positive pregnant women are at heightened risk of becoming lost to follow-up (LTFU) from HIV care. We examined LTFU before and after delivery among pregnant women newly diagnosed with HIV. METHODS: Observational cohort study of all pregnant women ≥18 years (N = 300) testing HIV positive for the first time at their first ANC visit between January and June 2010, at a primary healthcare clinic in Johannesburg, South Africa. Women (n = 27) whose delivery date could not be determined were excluded. RESULTS: Median (IQR) gestation at HIV testing was 26 weeks (21-30). Ninety-eight per cent received AZT prophylaxis, usually started at the first ANC visit. Of 139 (51.3%) patients who were ART eligible, 66.9% (95% CI 58.8-74.3%) initiated ART prior to delivery; median (IQR) ART duration pre-delivery was 9.5 weeks (5.1-14.2). Among ART-eligible patients, 40.5% (32.3-49.0%) were cumulatively retained through 6 months on ART. Of those ART-ineligible patients at HIV testing, only 22.6% (95% CI 15.9-30.6%) completed CD4 staging and returned for a repeat CD4 test after delivery. LTFU (≥1 month late for last scheduled visit) before delivery was 20.5% (95% CI 16.0-25.6%) and, among those still in care, 47.9% (95% CI 41.2-54.6%) within 6 months after delivery. Overall, 57.5% (95% CI 51.6-63.3%) were lost between HIV testing and 6 months post-delivery. CONCLUSIONS: Our findings highlight the challenge of continuity of care among HIV-positive pregnant women attending antenatal services, particularly those ineligible for ART.
    Tropical Medicine & International Health 02/2013; · 2.94 Impact Factor
  • Journal of Women s Health 02/2013; 22(22):113-120. · 1.42 Impact Factor
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    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.
    AIDS research and human retroviruses 02/2013; · 2.18 Impact Factor
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    ABSTRACT: We studied the immune response after starting antiretroviral treatment (ART) in 15,646 HIV-infected patients with or without tuberculosis (TB) at presentation in three ART programs in South Africa between 2003-2010. Patients presenting with TB had similar increases in CD4 cells compared to all other patients (adjusted difference 4.9 cells/µl per six months, 95% CI 0.2-9.7). Younger age, advanced clinical stage, female sex, and lower CD4 cell count at ART start were all associated with steeper CD4 slopes. In South Africa HIV-infected patients presenting with TB experience immune recovery after starting ART that is no worse than in other patients.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 01/2013; · 4.65 Impact Factor
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    ABSTRACT: Abstract Background: Treatment outcomes for antiretroviral therapy (ART) patients may vary by gender, but estimates from current evidence may be confounded by disease stage and adherence. We investigated the gender differences in treatment response among HIV-positive patients virally suppressed within 6 months of treatment initiation. Methods: We analyzed data from 7,354 patients initiating ART between April 2004 and April 2010 at Themba Lethu Clinic, a large urban public sector treatment facility in South Africa. We estimated the relations among gender, mortality, and mean CD4 response in HIV-infected adults virally suppressed within 6 months of treatment initiation and used inverse probability of treatment weights to correct estimates for loss to follow-up. Results: Male patients had a 20% greater risk of death at both 24 months and 36 months of follow-up compared to females. Older patients and those with a low hemoglobin level or low body mass index (BMI) were at increased risk of mortality throughout follow-up. Men gained fewer CD4 cells after treatment initiation than did women. The mean differences in CD4 count gains made by women and men between baseline and 12, 24, and 36 months were 28.2 cells/mm(3) (95% confidence interval [CI] 22.2-34.3), 60.8 cells/mm(3) (95% CI 71.1-50.5 cells/mm(3)), and 83.0 cells/mm(3) (95% CI 97.1-68.8 cells/mm(3)), respectively. Additionally, patients with a current detectable viral load (>400 copies/mL) and older patients had a lower mean CD4 increase at the same time points. Conclusions: In this initially virally suppressed population, women showed consistently better immune response to treatment than did men. Promoting earlier uptake of HIV treatment among men may improve their immunologic outcomes.
    Journal of Women s Health 01/2013; · 1.42 Impact Factor
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    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.
    PLoS ONE 01/2013; 8(3):e58117. · 3.73 Impact Factor
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    ABSTRACT: Recent WHO guidelines for resource-limited settings recommend tenofovir in first-line antiretroviral therapy (ART) yet there are suggestions that patients receiving nevirapine with tenofovir have worse outcomes than those receiving efavirenz. We sought to compare outcomes among those taking nevirapine vs. efavirenz with tenofovir and lamivudine. We analyzed data on ART naïve, non-pregnant patients, ≥18 years old without tuberculosis co-infection, initiating tenofovir with lamivudine and either nevirapine or efavirenz between April 1, 2010 and July 31, 2011 (when South Africa's public-sector use of tenofovir began) at Themba Lethu Clinic in South Africa. We measured virologic suppression (viral load <400 copies/ml), virologic failure (2 consecutive viral loads >1000 copies/ml), and attrition (death/loss to follow-up) all at 12 months after ART initiation. Modified Poisson regression with robust error estimation was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for predictors of each outcome. 2,254 patients were prescribed efavirenz, 131 nevirapine. Patients were followed a median (range) of 12.0 (0.1-12.0) person-months. 62.2% were female and median (IQR) age was 37.7 years (31.5-44.1). Patients prescribed efavirenz had similar initiating CD4 counts (median 132 for both regimens) but were somewhat more likely to be WHO Stage III or IV (39.6% vs. 33.6%) than those prescribed nevirapine. No difference in attrition was found (aRR: 0.83; 95% CI: 0.49-1.41). Among patients with ≥1 viral load within 1 year on ART, those prescribed nevirapine were as likely to reach virologic suppression (aRR: 0.97; 95% CI: 0.88-1.07) but more likely to experience virologic failure (aRR: 1.84; 95% CI: 1.02-3.31) than those prescribed efavirenz. Our results support the notion that, among patients prescribed tenofovir and lamivudine, virologic failure is more common among those taking nevirapine than among those taking efavirenz. Longer-term follow up and larger studies will be needed to confirm this finding.
    PLoS ONE 01/2013; 8(8):e71719. · 3.73 Impact Factor
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    ABSTRACT: Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. Between January 2001-January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm(3)) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71-4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95-5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08-4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7-52cells/mm(3)) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99-2.06) within the first 6-months of treatment. HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS.
    PLoS ONE 01/2013; 8(6):e64392. · 3.73 Impact Factor
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    ABSTRACT: Introduction: In April 2010, tenofovir replaced stavudine in public-sector first-line antiretroviral therapy (ART) in South Africa. The association of tenofovir with fewer side effects and toxicities compared to stavudine could translate to increased durability of tenofovir-based regimens. We evaluated changes over time in regimen durability at the Themba Lethu Clinic, Johannesburg, South Africa. Methods: This was a cohort analysis of treatment-naïve, non-pregnant adult patients initiated on ART between April 2004 and December 2011. First-line ART regimens before April 2010 consisted of stavudine or zidovudine with lamivudine and either efavirenz or nevirapine. Tenofovir was substituted for stavudine after April 2010. We evaluated the frequency and type of single-drug substitutions (excluding switches to second-line therapy). Cox models were used to evaluate the association of ART initiation year and antiretroviral drug type with single-drug substitutions in the first 12 months on treatment. Results: One thousand nine hundred and sixty-four (10%) substitutions occurred amongst 19,699 patients. Excluding 2004 (year of treatment roll-out), before 2010 one-year single-drug substitutions ranged from 10.0 to 13.1%. In 2011, well after integration of tenofovir, substitutions decreased to 5.6%. Single-drug substitution was lowest amongst patients on tenofovir (5.1%) versus zidovudine (11.3%), 30 mg stavudine (10.5%) or 40 mg stavudine (14.4%). Adjusted Cox models showed that patients initiating treatment between 2005 and 2010 (vs. 2011) had a twofold increased hazard of single-drug substitution, while those on zidovudine or stavudine had a two to threefold increase in single-drug substitution versus tenofovir patients in the first 12 months on ART. Conclusions: The decline in single-drug substitutions is associated with the introduction of tenofovir. Tenofovir use could improve regimen durability and treatment outcomes in resource-limited settings.
    Journal of the International AIDS Society 01/2013; 16(1):18794. · 3.94 Impact Factor
  • AIDS 01/2013; · 6.41 Impact Factor
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    ABSTRACT: Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.
    Journal of Tropical Medicine 01/2013; 2013:162950.

Publication Stats

403 Citations
255 Downloads
3k Views
204.96 Total Impact Points

Institutions

  • 2007–2014
    • University of the Witwatersrand
      • • Department of Internal Medicine
      • • Clinical HIV Research Unit (CHRU)
      • • Faculty of Health Sciences
      Johannesburg, Gauteng, South Africa
  • 2011–2013
    • Duke University
      Durham, North Carolina, United States
    • Universität Bern
      • Institute of Social and Preventive Medicine
      Bern, BE, Switzerland
  • 2012
    • Duke University Medical Center
      • Department of Obstetrics and Gynecology
      Durham, NC, United States
  • 2009–2010
    • Boston University
      • Center for Global Health and Development
      Boston, MA, United States