Suchergebnisse

Randomized trials play an important role in estimating the effect of a policy or social work program in a given population. While most trial designs benefit from strong internal validity, they often lack external validity, or generalizability, to the target population of interest. In other words, one can obtain an unbiased estimate of the study sample average treatment effect from a randomized trial; however, this estimate may not equal the target population average treatment effect if the study sample is not fully representative of the target population. This article provides an overview of existing strategies to assess and improve upon the generalizability of randomized trials, both through statistical methods and study design, as well as recommendations on how to implement these ideas in social work research.

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.

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.

BackgroundThe risk of squamous intra‐epithelial lesions (SIL) is higher in HIV‐positive women. As these women begin to live longer due to highly active antiretroviral therapy (HAART), their risk of cervical cancer may increase. Few data exist regarding the effect of HAART on the incidence and progression of SIL in HIV‐positive African women. The aim of this study was to evaluate the effect of HAART on the incidence and progression of SIL in HIV‐positive women in South Africa.MethodsA prospective observational study of HIV‐seropositive women was conducted over 5 years in an HIV treatment clinic in Johannesburg, South Africa. The participants consisted of 601 women on and off HAART who had repeat Pap smears greater than 6 months apart. The effect of HAART use on incidence and progression rates of SIL was determined using multivariate Poisson regression to obtain incidence rate ratios (IRRs), adjusted for age, CD4 count and other potential confounders.ResultsMedian follow‐up time was 445 days (inter‐quartile range 383, 671). The crude rate of incidence of any SIL was 15.9 episodes (95% confidence limit (CL) 12.7, 19.9) per 100 person‐years; the crude rate of all progression of cervical dysplasia among women was 13.5 episodes (95% CL 11.3, 16.1) per 100 person‐years. HAART use was associated with a robust reduction in the rate of incidence and progression of cervical lesions, adjusted IRR=0.55 (95% CL 0.37, 0.80). Sensitivity analyses confirmed this main association held for incidence and progression when they were considered separately, and that the result was not dependent on the length of HAART exposure.ConclusionHAART use was associated with a reduction in the rate of both incidence and progression of cervical lesions among HIV‐positive women.

BackgroundHIV testing rates in many hyper-endemic areas are lower than needed to curtail the HIV epidemic. New HIV testing strategies are needed to overcome barriers to traditional clinic based testing; HIV self-testing is one modality that offers promise in reaching individuals who experience barriers to clinic-based testing.MethodsWe conducted a randomized control trial among young women ages 18-26 living in rural Mpumalanga, South Africa where they were randomized in a 1:1 allocation to either the: (1) HIV Counseling and Testing (HCT) arm: an invitation to test at one of the 9 local government clinics where free HCT is provided and is standard of care (SOC), or (2) choice arm: choice of either a clinic-based HCT invitation or oral HIV Self-Testing (HIVST) kits. Depending on the arm, participants were also provided either: (1) 4 HCT invitations to provide to peers/partners for HIV testing at one of the 9 local clinics, or (2) 4 HIV self-test kits to provide to peers/partners (thus 5 total HIVST kits or HCT invitations). Young women were asked to return 3 months and 9 months after enrollment to assess testing uptake and invitation or kit distribution to peers and partners and experiences with testing. Peers and partners who were reported by index participants to have received kits/invitations during follow-up visits were also invited to attend a study visit to assess their testing experiences. The trial is registered at clinical trials.gov NCT03162965.Findings287 young women were enrolled and randomized, with 146 randomized to the HCT arm and 141 to the choice (HCT or HIVST) arm. Of those randomized to the choice arm, over 95% (n=135) chose the HIV self-testing kit and only 6 individuals chose HCT. At the 3-month follow-up visit, 92% of index participants in the choice arm reported having tested for HIV compared to 43% of participants in the HCT arm, resulting in a significant risk difference of 49% (95% CI 40%, 58%). By 9 months, this difference decreased to a risk difference of 25% (95% CI 17%, 33%) between ...

BackgroundHIV testing rates in many hyper-endemic areas are lower than needed to curtail the HIV epidemic. New HIV testing strategies are needed to overcome barriers to traditional clinic based testing; HIV self-testing is one modality that offers promise in reaching individuals who experience barriers to clinic-based testing.MethodsWe conducted a randomized control trial among young women ages 18-26 living in rural Mpumalanga, South Africa where they were randomized in a 1:1 allocation to either the: (1) HIV Counseling and Testing (HCT) arm: an invitation to test at one of the 9 local government clinics where free HCT is provided and is standard of care (SOC), or (2) choice arm: choice of either a clinic-based HCT invitation or oral HIV Self-Testing (HIVST) kits. Depending on the arm, participants were also provided either: (1) 4 HCT invitations to provide to peers/partners for HIV testing at one of the 9 local clinics, or (2) 4 HIV self-test kits to provide to peers/partners (thus 5 total HIVST kits or HCT invitations). Young women were asked to return 3 months and 9 months after enrollment to assess testing uptake and invitation or kit distribution to peers and partners and experiences with testing. Peers and partners who were reported by index participants to have received kits/invitations during follow-up visits were also invited to attend a study visit to assess their testing experiences. The trial is registered at clinical trials.gov NCT03162965.Findings287 young women were enrolled and randomized, with 146 randomized to the HCT arm and 141 to the choice (HCT or HIVST) arm. Of those randomized to the choice arm, over 95% (n=135) chose the HIV self-testing kit and only 6 individuals chose HCT. At the 3-month follow-up visit, 92% of index participants in the choice arm reported having tested for HIV compared to 43% of participants in the HCT arm, resulting in a significant risk difference of 49% (95% CI 40%, 58%). By 9 months, this difference decreased to a risk difference of 25% (95% CI 17%, 33%) between arms (96% in the choice arm and 72% in the HCT arm). Participants in the choice arm were also more likely to invite peers and partners to test compared to the HCT arm (94% vs. 76% or an average of 4.97 vs 2.79 tests). Few male partners were invited to test by index participants; however, index participants in the choice arm were more likely to have their male partners test than index participants in the HCT arm (RR 2.99, 95% CI 1.45, 6.16).InterpretationWhen given a choice between clinic-based HIV testing and HIV oral self-testing, the overwhelming majority of young women chose HIVST. In addition, those offered a choice of HIV testing modality were much more likely to test, distribute test kits to peers and partners, and to have peers and partners who reported testing compared to the HCT arm. Self-testing offers an important opportunity to significantly increase testing rates among young women and their peers and partners compared to clinic-based HCT. Other strategies to reach men with testing are needed.FundingUS National Institutes of Health.

BACKGROUND: HIV testing rates in many hyper-endemic areas are lower than needed to curtail the HIV epidemic. New HIV testing strategies are needed to overcome barriers to traditional clinic based testing; HIV self-testing is one modality that offers promise in reaching individuals who experience barriers to clinic-based testing. METHODS: We conducted a randomized control trial among young women ages 18-26 living in rural Mpumalanga, South Africa where they were randomized in a 1:1 allocation to either the: (1) HIV Counseling and Testing (HCT) arm: an invitation to test at one of the 9 local government clinics where free HCT is provided and is standard of care (SOC), or (2) choice arm: choice of either a clinic-based HCT invitation or oral HIV Self-Testing (HIVST) kits. Depending on the arm, participants were also provided either: (1) 4 HCT invitations to provide to peers/partners for HIV testing at one of the 9 local clinics, or (2) 4 HIV self-test kits to provide to peers/partners (thus 5 total HIVST kits or HCT invitations). Young women were asked to return 3 months and 9 months after enrollment to assess testing uptake and invitation or kit distribution to peers and partners and experiences with testing. Peers and partners who were reported by index participants to have received kits/invitations during follow-up visits were also invited to attend a study visit to assess their testing experiences. The trial is registered at clinical trials.gov NCT03162965. FINDINGS: 287 young women were enrolled and randomized, with 146 randomized to the HCT arm and 141 to the choice (HCT or HIVST) arm. Of those randomized to the choice arm, over 95% (n=135) chose the HIV self-testing kit and only 6 individuals chose HCT. At the 3-month follow-up visit, 92% of index participants in the choice arm reported having tested for HIV compared to 43% of participants in the HCT arm, resulting in a significant risk difference of 49% (95% CI 40%, 58%). By 9 months, this difference decreased to a risk difference of 25% (95% CI 17%, 33%) ...