Suchergebnisse

BackgroundAdherence to care and treatment are essential for HIV‐infected individuals to benefit from antiretroviral therapy (ART). We sought to quantify the effects on treatment outcomes of missing visits soon after initiating ART.MethodsWe analyzed data from HIV‐infected patients initiating ART at Themba Lethu Clinic, Johannesburg, South Africa, from April 2004 to August 2008. We used log‐binomial regression to evaluate the relative risk of missing visits during the first six months of ART on immunological response and virologic suppression. Cox models were used to evaluate the relationship between missed visits and mortality and loss to follow up over 12 months.ResultsOf 4476 patients, 65% missed no visits, while 26% missed one visit, 7% missed two and 1.6% missed three or more visits during the first six months on treatment. Patients who missed three or more medical or antiretroviral (ARV) visits had a two‐fold increased risk of poor CD4 response by six months, while the risk of failing to achieve virologic suppression by six months increased two‐ to five‐fold among patients who missed two and three or more medical or ARV visits. Adjusted Cox models showed that patients who missed two (HR 2.1; 95% CI: 1.0‐4.3) and three or more (HR 4.7; 95% CI: 1.4‐16.2) medical visits had an increased risk of death, while those who missed two ARV (HR 3.8; 95% CI: 2.5‐5.8) or three or more medical (HR 3.0; 95% CI: 1.1‐8.1) visits had an increased risk of loss to follow up.ConclusionsThirty‐five percent of patients missed one or more visits in the first six months on treatment, increasing their risk of poorer outcomes. These patients could be targeted for additional adherence counselling to help improve ART outcomes.

BackgroundAs stavudine remains an important and widely prescribed drug in resource‐limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.MethodsWe analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six‐ and/or 12‐month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.ResultsBetween 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13‐2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86‐5.25), lipoatrophy (OR 11.8; 95% CI 3.2‐43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83‐18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.ConclusionsLower stavudine dosage is associated with fewer reports of several stavudine‐associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.

BackgroundCurrent guidelines for providing antiretroviral therapy (ART) in South Africa's public sector programme call for switching patients from first‐line to second‐line treatment upon virologic failure as indicated by two consecutive viral loads above 5000 copies/ml, but without laboratory evidence of viral resistance. We modelled the net cost of adding resistance testing for patients with virological failure and retaining patients without resistance on first‐line therapy, rather than switching all failures to second‐line therapy.MethodsCosts were estimated for three scenarios: routine maintenance (standard care without resistance testing, switch all failures to second line); resistance testing (resistance test for patients with failure, switch those with resistance); and limited testing (resistance test for patients with failure in the first three years, switch those with resistance). A Markov model was used to estimate the cost of each arm over five years after first line initiation. Rates of treatment failure, viral resistance and treatment costs were estimated with primary data from a large HIV treatment cohort at a public facility in Johannesburg. Future costs were discounted at 3%.ResultsVirological failure rates over five years were 19.8% in routine maintenance and 20.2% in resistance testing and limited testing; 16.8% and 11.4% of failures in routine and limited testing, respectively, did not have any resistance mutations, resulting in 3.1% and 2.0% fewer patients switching to second‐line ART by the end of five years. Treatment costs were estimated at US$526 and $1268 per patient per year on first‐line and second‐line therapy, respectively; a resistance test cost $242. The total average cost per patient over five years was $2780 in routine maintenance; $2775 in resistance testing; and $2763 in limited testing.ConclusionsIncorporating resistance testing into treatment guidelines in South Africa is potentially cost‐neutral and can identify other reasons for failure, conserve treatment options, and generate information about emerging resistance patterns.

IntroductionThe prognostic role of CD4 response in the first six months of treatment in patients achieving early viral suppression during HIV treatment is unclear.MethodsThis 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.ResultsA 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.ConclusionsPatients 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.

BackgroundClinical, immunologic and virologic outcomes at large HIV/AIDS care clinics in resource poor settings are poorly described beyond the first year of highly active antiretroviral treatment (HAART). We aimed to prospectively evaluate long‐term treatment outcomes at a large scale HIV/AIDS care clinic in South Africa.MethodsCohort study of patients initiating HAART between April 1, 2004 and March 13, 2007, and followed up until April 1, 2008 at a public HIV/AIDS care clinic in Johannesburg, South Africa. We performed time to event analysis on key treatment outcomes and program impact parameters including mortality, retention in care, CD4 count gain, virologic success and first line regimen durability.Results7583 HIV‐infected patients initiated care and contributed to 161,000 person months follow up. Overall mortality rate was low (2.9 deaths per 100 person years, 95% CI 2.6‐3.2), but high in the first three months of HAART (8.4 per 100 person years, 95% CI 7.2‐9.9). Long‐term on‐site retention in care was relatively high (74.4% at 4 years, 95%CI 73.2‐75.6). CD4 count was above 200 cells/mm3 after 6 months of treatment in almost all patients. By the fourth year of HAART, the majority (59.6%, 95%CI 57.8‐61.4) of patients had at least one first line drug (mainly stavudine) substituted. Women were twice as likely to experience drug substitution (OR 1.97, 95% CI 1.80‐2.16). By 6 months of HAART, 90.8% suppressed virus below 400 copies. Among those with initial viral suppression, 9.4% (95% CI 8.5‐10.3%) had viral rebound within one year of viral suppression, 16.8% (95% CI 15.5‐18.1) within 2 years, and 20.6% (95% CI 18.9‐22.4) within 3 years of initial suppression. Only 10% of women and 13% of men initiated second line HAART.ConclusionDespite advanced disease presentation and a very large‐scale program, high quality care was achieved as indicated by good long‐term clinical, immunologic and virologic outcomes and a low rate of second line HAART initiation. High rates of single drug substitution suggest that the public health approach to HAART could be further improved by the use of a more durable first line regimen.

Objective: There are 350 million hepatitis B carriers world-wide. Mono-infection with Hepatitis B in urban South Africa has been estimated at approximately 1%. The exact prevalence rate of hepatitis B in the HIV population has not been well established. Hepatitis B screening is not standard of care in the HIV government clinics. Coinfection with hepatitis B and HIV can influence ARV treatment and prognosis of both of these diseases. Evaluating the Hepatitis B/HIV coinfection prevalence was the goal of this study. Design: This is the first prospective observational report of the prevalence of hepatitis B/HIV co infection in South Africa. Patients were recruited from a HIV clinic in regional hospital in Johannesburg. Previous hepatitis B serology could not have been previously done. Standard hepatitis B serology was performed. Results: 502 participants were screened. The cohort's average age was 37 +/- 9 years and an average CD4 count of 128 cells/mm3 Twenty- four (4.8%) were hepatitis B surface antigen positive. 47% of the participants showed some evidence of hepatitis B exposure. The risk of hepatitis B coinfecition was not significantly different by sex, race, CD4 count or age. Liver function tests were not a good predictor of hepatitis B infection. Conclusion: The coinfection rate of hepatitis B/HIV as defined by hepatitis B surface antigen positivity is 5X the prevalence of non HIV infected individuals in urban SA. With a 5% hepatitis B/HIV coinfection rate, consideration to increase accessibility of Truvada for first line treatment for this population is imperative.

IntroductionPrevious research has raised concerns that patients given nevirapine (NVP)‐based regimens experience more virologic failure than patients given efavirenz (EFV)‐based regimens. We investigated this hypothesis in a cohort of HIV‐positive patients at a large HIV treatment clinic in South Africa.MethodsAll antiretroviral therapy (ART)‐naïve non‐pregnant patients, ≥18 years old, without tuberculosis, who initiated treatment with either NVP or EFV from April 2004 to August 2011 at the Themba Lethu Clinic in Johannesburg, South Africa, were included. Log‐binomial regression and modified Poisson regression were used to estimate risk ratios (RR) with 95% confidence intervals (CI) for predictors of virologic failure, virologic suppression, and loss to follow‐up (LTF), whereas a Cox proportional hazards model was used to estimate the risk of death, all within one year.ResultsOf 12,840 included patients, 62.0% were female and the median baseline CD4 count was 98 cells/mm3 (36–169). Of these patients, 93.2% initiated an EFV‐based regimen. After adjusting for baseline characteristics, no difference in death (adjusted Hazards Ratio (aHR): 0.92; 95% CI: 0.68–1.25), LTF (adjusted Risk Ratio (aRR): 1.00; 95% CI: 0.79–1.25), nor suppression (aRR: 0.98; 95% CI: 0.95–1.00) at one year was found between regimens. Among patients with ≥1 viral load ≥4 months after ART initiation, 4% (n=350) experienced virologic failure within 12 months of initiation. Patients initiating NVP‐based regimens were 60% more likely to fail than patients initiating EFV‐based regimens (aRR: 1.58; 95% CI: 1.13–2.22).ConclusionsIn this cohort, patients initiating NVP‐based regimens experienced more virologic failure than patients initiating EFV‐based regimens. Future guidelines should consider the implications of different efficacy profiles when making recommendations for which drugs to prioritize.

IntroductionSeveral studies from resource‐limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers.MethodsWe analyzed data from HIV‐positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as ≥2 consecutive HIV‐RNA viral loads >400 copies/ml following suppression ≤400 copies/ml. We used Cox‐proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut‐off at the point with the highest sensitivity and specificity (i.e. ≤4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut‐offs, with and without CD4 criteria (CD4 <100 cells/mm3; CD4 < baseline; >30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure.ResultsWe matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count <100 cells/mm3, WHO stage III/IV and albumin) and laboratory and clinical follow‐up data (drop in haemoglobin, mean cell volume (MCV) <100 fl, CD4 count <200 cells/mm3, new or recurrent WHO stage III/IV condition, diagnosis of new condition or symptom and regimen change). Overall, 51.4% had a score 51.4% had a score ≥4 and 48.6% had a score <4. A predictor score including CD4 criteria performed better than a score without CD4 criteria and better than WHO clinico‐immunological criteria or WHO clinical staging to predict virologic failure (sensitivity 57.1% vs. 40.9%, 25.2% and 20.9%, respectively).ConclusionsPredictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource‐limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes.

IntroductionIn 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.MethodsThis 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.ResultsOne 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.ConclusionsThe 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.

AbstractIntroduction: Implementation of safer conception services for HIV‐affected couples within primary healthcare clinics in resource‐limited settings remains limited. We review service utilization and safer conception strategy uptake during the first three years of Sakh'umndeni, which is a safer conception clinic in South Africa.Methods: Sakh'umndeni is located at Witkoppen Health and Welfare Centre, a high‐volume primary healthcare clinic in northern Johannesburg. Men and women desiring to conceive in less than or equal to six months and in relationships in which one or both partners are living with HIV are eligible for safer conception services. Clients receive a baseline health assessment and counselling around periconception HIV risk reduction strategies and choose which strategies they plan to use. Clients are followed‐up monthly. We describe client service utilization and uptake and continuation of safer conception methods. Factors associated with male partner attendance are assessed using robust Poisson regression.Results: Overall 440 individuals utilized the service including 157 couples in which both partners attended (55%) and 126 unaccompanied female partners. Over half of the couples (55%) represented were in serodiscordant/unknown status relationships. Higher economic status and HIV‐negative status of the women increased male partner involvement, while HIV‐negative status of the men decreased male involvement. Regarding safer conception strategies, uptake of antiretroviral therapy initiation (90%), vaginal self‐insemination among partnerships with HIV‐negative men (75%) and timed condomless intercourse strategies (48%) were variable, but generally high. Overall uptake of pre‐exposure prophylaxis (PrEP) was 23% and was lower among HIV‐negative men than women (7% vs. 44%, p < 0.001). Male medical circumcision (MMC) was used by 28% of HIV‐negative men. Over 80% of clients took up at least one recommended safer conception strategy. Continuation of selected strategies over attempted conception attempts was >60%.Conclusions: Safer conception strategies are generally used by clients per recommendations. High uptake of strategies suggests that the proposed combination prevention methods are acceptable to clients and appropriate for scale‐up; however, low uptake of PrEP and MMC among HIV‐negative men needs improvement. Targeted community‐based efforts to reach men unlinked to safer conception services are needed, alongside streamlined approaches for service scale‐up within existing HIV and non‐HIV service delivery platforms.

IntroductionA substantial number of patients with HIV in South Africa have failed first‐line antiretroviral therapy (ART). Although individual predictors of first‐line ART failure have been identified, few studies in resource‐limited settings have been large enough for predictive modelling. Understanding the absolute risk of first‐line failure is useful for patient monitoring and for effectively targeting limited resources for second‐line ART. We developed a predictive model to identify patients at the greatest risk of virologic failure on first‐line ART, and to estimate the proportion of patients needing second‐line ART over five years on treatment.MethodsA cohort of patients aged ≥18 years from nine South African HIV clinics on first‐line ART for at least six months were included. Viral load measurements and baseline predictors were obtained from medical records. We used stepwise selection of predictors in accelerated failure‐time models to predict virologic failure on first‐line ART (two consecutive viral load levels >1000 copies/mL). Multiple imputations were used to assign missing baseline variables. The final model was selected using internal‐external cross‐validation maximizing model calibration at five years on ART, and model discrimination, measured using Harrell's C‐statistic. Model covariates were used to create a predictive score for risk group of ART failure.ResultsA total of 72,181 patients were included in the analysis, with an average of 21.5 months (IQR: 8.8–41.5) of follow‐up time on first‐line ART. The final predictive model had a Weibull distribution and the final predictors of virologic failure were men of all ages, young women, nevirapine use in first‐line regimen, low baseline CD4 count, high mean corpuscular volume, low haemoglobin, history of TB and missed visits during the first six months on ART. About 24.4% of patients in the highest quintile and 9.4% of patients in the lowest quintile of risk were predicted to experience treatment failure over five years on ART.ConclusionsAge, sex, CD4 count and having any missed visits during the first six months on ART were the strongest predictors of ART failure. The predictive model identified patients at high risk of failure, and the predicted failure rates over five years closely reflected actual rates of failure.