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A Randomized, Multicenter, Open-Label Study of Poly-L-Lactic Acid for HIV-1 Facial Lipoatrophy

JAIDS Journal of Acquired Immune Deficiency Syndromes:Volume 46(5)15 December 2007pp 581-589

Carey, Dianne L MPH*; Baker, David MB, ChB†; Rogers, Gary D MBBS, PhD‡; Petoumenos, Kathy PhD*; Chuah, John MBBS, BSc (Med) Hons§; Easey, Nicole BApplSc (Med Imaging)‖; Machon, Kirsty BA (Hons), MA¶; Cooper, David A DSc, MD*‖; Emery, Sean PhD*; Carr, Andrew MD‖; for the Facial LipoAtrophy Study in HIV Investigators

>From the *National Centre in HIV Epidemiology and Clinical Research, The University of New South Wales, Sydney, Australia; †407 Doctors, Sydney, Australia; ‡Secretariat of the Pacific Community, Noumea, New Caledonia; §Gold Coast Sexual Health Clinic, Miami, Australia; ‖St. Vincent's Hospital, Sydney, Australia; and the ¶National Association of People Living with HIV/AIDS, Sydney, Australia.

“In summary, we showed in a multicenter, open-label, randomized controlled trial with objective endpoints that PLA treatment in HIV-infected adults with moderate or severe facial lipoatrophy achieved only modest increases in facial thickness but not in facial volume. In contrast, patient-perceived benefits were significant in terms of aesthetic improvement and increased well-being, social functioning, and quality of life. PLA does not address fat loss in other body regions. Restoration of lost fat mass is gradual. In the interim, further well-designed comparative studies with objectively assessed endpoints are needed to ascertain the optimal treatment for HIV facial lipoatrophy.”


Abstract
Background: Facial lipoatrophy can stigmatize and can reduce quality of life, self esteem, and antiretroviral adherence. Poly-L-lactic acid (PLA) injections seem safe and effective, but no randomized study has included objective endpoints.

Methods: HIV-positive adults with moderate/severe facial lipoatrophy were randomized to 4 open-label PLA treatments administered every 2 weeks from week 0 (immediate group, n = 51) or after week 24 (deferred group, n = 50). The primary endpoint was mean change in facial soft tissue volume (FSTV), as assessed by spiral computed tomography. Analyses were by intention to treat.

Results: At week 24, mean changes in FSTV were 0 cm3 in the intermediate group and -10 cm3 in the deferred group (between-group difference of 10 [95% confidence interval (CI): -7 to 28] cm3; P = 0.24). The immediate group had a greater mean change in soft tissue depth at the maxilla (2.2 mm [95% CI: 1.6 to 2.9]; P < 0.0001) and base of the nasal septum (1.0 mm [95% CI: 0.3 to 1.6]; P = 0.003) levels. PLA did not have an impact on peripheral fat mass, viral load, or antiretroviral adherence. Patient and physician subjectively assessed facial lipoatrophy severity (P < 0.0001), 2 of 8 Short Form-36 Health Survey and 2 of 5 Multidimensional Body-Self Relations Questionnaire-Appearance Scales, scores improved significantly. The median duration of treatment-related adverse events was 2 (interquartile range: 1 to 3) days.

Conclusions: PLA did not increase FSTV, although tissue thickness in injection planes increased modestly, an improvement observed by patients. PLA was safe and well tolerated. Facial lipoatrophy severity and some quality-of-life domains improved.

HIV lipodystrophy (peripheral lipoatrophy and relative central fat accumulation) can be disfiguring and socially stigmatizing and may result in reduced antiretroviral adherence.1,2 Facial lipoatrophy is the most distressing manifestation.3 Apart from the modest benefits of thymidine-based nucleoside analogue cessation, there is no proven therapy for lipoatrophy.4-10 Even with nucleoside analogue cessation, changes in facial lipoatrophy were not observed with standard methods.6,11

Plastic surgery and cosmetic procedures may restore facial fat volume. Permanent and biodegradable soft tissue filling agents have been investigated.12,13 Poly-L-lactic acid (PLA; Sculptra; Dermik Laboratories, Berwyn, PA), which has been approved in Europe and the United States for use in HIV facial lipoatrophy, is used most commonly. PLA is a synthetic, biodegradable, immunologically inert, resorbable polymer. It has been widely and safely used for many years in surgical devices such as resorbable sutures, surgical meshes, and plate and pin implants in craniofacial and orthopedic surgery and as vectors for injectable slow-release drug delivery systems.14,15 After injection, PLA microparticles may stimulate collagen production, which leads to a gradual and progressive increase in volume of the lipoatrophic area.16

Open-label studies have demonstrated the safety of PLA injections in HIV-infected adults.17-25 PLA efficacy is less clear, because all studies were single site, most were small, and all were uncontrolled or had subjective efficacy endpoints.17-19,21-25 We undertook a randomized, multicenter, open-label, 24-week study with a 96-week total follow-up comparing immediate versus deferred deep subcutaneous injections of PLA in adults with antiretroviral-induced facial lipoatrophy. The primary objective was to determine the effect of 4 bilateral PLA treatments administered every 2 weeks on facial soft tissue volume (FSTV) over 24 weeks with volumetric computed tomography (CT). Other endpoints comprised safety, body composition measures, quality of life, and antiretroviral adherence.

DISCUSSION
Four bilateral PLA treatments administered by deep subcutaneous injection every 2 weeks did not increase FSTV after 24 weeks in HIV-infected lipodystrophic adults with extensive antiretroviral exposure and moderate or severe facial lipoatrophy. Small improvements in objectively assessed facial soft tissue thickness around the planes of injection were demonstrated. Clinicians and patients perceived significant treatment benefits with reductions in facial lipoatrophy severity assessed in treated subjects relative to controls. Some quality-of-life scores also improved.

There is no validated measure of facial thickness. FSTV had not been used previously but was chosen because it is an unbiased objective measure. The lack of improvement in FSTV at week 24 may be attributable to several factors. First, the study may have not been adequately powered. Because there were no normative data, we were uncertain of the expected change, and thus based our sample size calculation on the results of an earlier randomized study,18 where a statistically significant difference in improvement in patient visual analog assessment of 47% in the treatment arm versus 7% in the placebo arm was demonstrated at week 12. We chose a more conservative estimate of 50 subjects per arm, which gave 80% power to detect a difference in the proportion with a clinically relevant improvement in cheek volume to 10% in the placebo arm versus 35% in the treatment arm. At week 24, however, only 16% of treated subjects and 10% of deferred subjects had a >10% increase in FSTV. If the observed differences were accurate, we would have required 525 subjects per arm to detect a significant between-group difference in FSTV at week 24. Second, the procedure may be more variable than envisaged. Because subjects were spread geographically, 9 CT scanning sites were required. At each imaging site, a single operator acquired the data using the same equipment and software at each visit. Although baseline scans were quality assessed, failure to reconstruct the data set at week 24 to reflect baseline image parameters could produce measurement error. Finally, it is possible that PLA is not as efficacious as previously believed. At week 24, FSTV remained unchanged in PLA recipients but had decreased in untreated subjects, suggesting that PLA benefits may lie in its ability to prevent further deterioration in treated areas.

The heterogeneity of studies that have investigated the use of PLA in HIV facial lipoatrophy makes efficacy comparisons difficult. Treatment numbers vary enormously, with many studies adjusting vial numbers based on subjectively assessed baseline facial lipoatrophy severity or to achieve a subjectively assessed satisfactory result or predefined outcome.17,19-25 Only 1 study administered a fixed number of treatments.18 Across studies, the number of treatments ranged from 1 to 8, with mean/medians of 4 or 5. Heterogeneity of study subjects, facial lipoatrophy severity and its assessment, or lack of these data adds additional complexity. Although most subjects were white men aged 41 to 49 years, only 1 study used a validated lipodystrophy assessment tool27 to assess facial lipoatrophy severity.18 Apart from an ultrasound-assessed facial fat thickness threshold,17 the remaining studies utilized a site-specific scale with patient and/or clinician assessment. Because these open-label studies all lacked objective lipodystrophy data, comparisons are problematic.

Significant increases in facial thickness were observed at 2 planes, the maxilla and base of the nasal septum, which were the approximate planes of injection, but the increases were less than those recorded using sonography in previous studies.17,18,23,24 In these studies, measurements were made predominantly at the nasolabial folds and showed broad interstudy variability with changes of 4.4 mm at 2 months23 and 3.5 to 6.4 mm at 24 weeks17,18,24 after 4 or 6, 4 to 5, 3, and a median of 5 (range: 2 to 8) bilateral PLA treatments, respectively. Our results are similar to those obtained using 3-D photographs with 3-D computerized reconstruction of the face to measure dermal thickness.22 In 49 patients who received a median of 5 (range: 1 to 7) PLA treatments, the median increase in dermal thickness from baseline to the end of treatment (median = 2.3 [range: 0.5 to 7] months) was 1.9 (range: 0.4 to 5.5) mm. At the last follow-up assessment, a median of 12 (range: 1 to 27) months after the first PLA injection, the maximal increase in dermal thickness was 2.4 (range: 0.7 to 6.1) mm in the right cheek and 2.2 (range: 0.9 to 5.9) mm in the left.22 Calipers were used to assess skin thickness changes in the malar region (n = 99); however, because the authors reported only mean percent change from baseline at 6 months (59.2%), comparison with other studies is difficult.19 None of these measurement methods has been validated, perhaps assisting to explain the broad interstudy variability in outcomes. Because measurement reproducibility is operator dependent, it requires consistency in measurement positioning, which is made more difficult by the absence of facial landmarks. The shortcomings of facial sonography were highlighted in an earlier study, which showed it to be a poor measure of facial lipoatrophy.11

Despite only modest improvements in objectively assessed facial thickness, patients and clinicians perceived significant improvements. This observer bias results from the open-label design of the study and was observed in an earlier lipodystrophy study, where despite significant reductions in limb fat as assessed by DEXA, lipoatrophy severity was perceived to have improved significantly.35 In the current study, these perceptions were supported by a significant association between perceived improvements and objectively assessed increases in facial thickness. The lack of change in subjectively assessed lipodystrophy and its severity was supported by no difference in other objectively assessed body composition parameters. Additionally, the lack of between-group differences in limb fat mass and limb fat percent suggests that the observed facial differences were attributable to PLA treatment and not to a change in overall lipoatrophy.

The associations observed between the objectively assessed linear measures and patient subjective assessment, and between patient and physician subjective assessments, suggest that there is a treatment benefit. The lack of correlation between change in the objective primary endpoint, FSTV, and the secondary subjective endpoints is therefore of interest. The scanning landmarks (midorbit and angle of mandible) produced a volume substantially greater than the area where PLA was injected. Because increases in tissue depth in the injection plane were modest, it is possible that the resultant volumetric increases may not have been detected, particularly if, as mentioned previously, the procedure was more variable than anticipated.

The psychosocial impact of lipodystrophy is well described.36 This study used well-validated quality-of-life tools to assess the impact of PLA treatment on participants' health status and body image. Improvements in social function and mental health scores of the SF-36 provided additional evidence of patient-perceived treatment benefits. Our results contrast with those of an earlier study in which the SF-36 mental health score did not change after PLA treatment.22 Interesting, all SF-36 scores in the control group were reduced, perhaps reflecting despondency at being randomized to deferred treatment. Improvements in body self-image subscales of the MBSRQ-AS were also observed. Treated patients reported less dissatisfaction with their overall physical appearance and with most body areas at week 24 than control subjects.

PLA injections were safe and well tolerated. Although most patients experienced at least 1 procedure/product-related adverse event, most were of low grade and transient consistent with those observed in previous clinical studies.17,18,22 The incidence of injection-site nodules (12%) is comparable to that reported in other HIV studies.19,22,25 Although considerably lower than the incidences of 31% to 52% reported previously,17,24,37 it is higher than that found by other investigators (0% to 6%).19,21,23 Onset times for nodules of 2 to 9 months22 and a median of 7 months26 after the first injection have been reported; therefore, it is possible that with longer follow-up, the incidence reported here may increase.

There are limitations to this study. Most participants were white men, reflecting the HIV epidemic in Australia. There are no data describing normal FSTV in men; thus, we could not determine to what extent facial lipoatrophy normalized. Nevertheless, FSTV did not change, suggesting that additional PLA treatments might provide some benefit.

In summary, we showed in a multicenter, open-label, randomized controlled trial with objective endpoints that PLA treatment in HIV-infected adults with moderate or severe facial lipoatrophy achieved only modest increases in facial thickness but not in facial volume. In contrast, patient-perceived benefits were significant in terms of aesthetic improvement and increased well-being, social functioning, and quality of life. PLA does not address fat loss in other body regions. Restoration of lost fat mass is gradual. In the interim, further well-designed comparative studies with objectively assessed endpoints are needed to ascertain the optimal treatment for HIV facial lipoatrophy.


METHODS
Participants
Participants were recruited at 18 clinical sites (primary care, n = 11; hospital outpatient, n = 7) around Australia. Eligible participants had documented HIV-1 infection, were aged at least 18 years, had received combination antiretroviral therapy (ART), and had moderate or severe facial lipoatrophy with lipodystrophy at 1 or more other sites (arms, legs, abdomen, or buttocks). Current ART had to be unchanged for at least 12 weeks, or for subjects not on therapy, there should be no intent to recommence before week 24. Women of child-bearing potential had a negative pregnancy test result and were using contraception. Patients were ineligible if they had an active AIDS-defining illness, HIV wasting syndrome, active herpes labialis, any facial skin disorder, any coagulopathy, or previous treatment for facial lipoatrophy. Anabolic steroids (except testosterone replacement for hypogonadism), oral glucocorticosteroids at greater than replacement dose (7.5 mg of prednisolone daily or equivalent), anticoagulant therapies, growth hormone, or other agents to increase appetite or improve weight were not permitted.

All participants provided written informed consent after approval by each site's local human research ethics committee.

Interventions
The study randomized 100 eligible patients to receive 4 open-label PLA treatments (1 vial [150 mg] per cheek) every 2 weeks with a minimum 14-day interval between treatments commencing at week 0 (immediate group) or after a delay period of 24 weeks (deferred group). The immediate group received bilateral PLA injections at weeks 0, 2, 4, and 6 administered at a single surgical site in each of the 4 participating Australian states according to a common protocol. PLA vials were reconstituted to 5 mL;26 after an infraorbital nerve block (1 mL of lignocaine 2% with adrenaline), aliquots of 0.1 to 0.3 mL were deposited deep into the subcutaneous tissue in a predefined buccal area below the orbital margin (Fig. 1). After administration of the contents of 1 vial into each cheek, the injected areas were massaged firmly to promote even distribution of PLA. Participants were instructed to repeat the massage procedure 3 times daily for at least 3 days after each treatment. Management guidelines for PLA-related adverse events included treatment delay or termination. PLA cessation was mandatory for grade 4 (very severe or life-threatening) events considered definitely, probably, or possibly related to PLA. Antiretroviral drug substitution was permitted for on-study adverse events or virologic failure. Randomization using minimization was performed by a single statistician at the National Centre in HIV Epidemiology and Clinical Research (NCHECR), Sydney, Australia, and was stratified by age, facial lipoatrophy severity, current protease inhibitor (PI) use, current thymidine analogue reverse transcriptase inhibitor (tNRTI) use, and surgeon. Lipoatrophy severity was assessed and scored by physical examination and patient report.27,28 Additionally, patient and physician assessment of facial lipoatrophy severity was made using a validated facial lipodystrophy picture scale (0 = normal, 1 = mild, 2 = moderate, and 3 = severe) with accompanying descriptions and facial diagrams,18 as described previously.27,28

Assessments
At screening, demographic details, ART, and concomitant medication were recorded. Participants were seen at week -1, at weeks 1, 3, 5, and 7 for postprocedure and safety review if in the immediate arm, and at weeks 12 and 24. Safety assessments included clinical adverse events, physical examination, concomitant drugs, complete blood cell count and coagulation screen, plasma HIV-1 RNA and T-lymphocyte subsets, and serum _-human chorionic gonadotrophin (pregnancy test) in women. At screening and week 24, spiral CT of the head was performed to quantify total FSTV of the region defined superiorly by the midorbit and inferiorly by the angle of mandible according to a common protocol. Participants were positioned supine and scanned parallel to the hard palate without gantry tilt. After spiral acquisition, 61 symmetric images were created in the axial plane at 1-mm thickness such that the middle image (image 31) was parallel to and at the level of the hard palate. Using the axial data and protocol-defined bony landmarks, 4 images were identified; using the measurement tool, bilateral baselines were then drawn on them as follows: symphysis mentis to the lateral aspect of each temporomandibular joint; anterior nasal spine to the lateral aspect of the ramus of each mandible; most anterior part of the bony nasal septum to the anterior aspect of the maxillary antrum; and lateral aspect of the temporal bone at the level of the optic nerve. The maximum distance from each baseline to the skin line was recorded as the mandible, base of nasal septum, maxilla, and orbit measurements, respectively (see Fig. 1). Volumetric assessment was performed using 3-dimensional (3-D) postprocessing software. A protocol-defined rectangular region of interest was defined on image 31 (midslice) and by use of appropriate Hounsfield units volumetric soft tissue measurements obtained. All baseline CT scans, linear measurements, and soft tissue volumes were quality reviewed at a single radiology site to ensure adherence to the common protocol, and any not considered adequate were repeated.

Body composition was measured by dual-energy x-ray absorptiometry (DEXA) at screening and week 24 to determine total and regional body fat and lean tissue (apart from the head) according to a standard protocol.4,28 Other objective body composition measures were weight, body mass index (BMI), and hip and waist circumferences. Subjective measures of lipodystrophy severity were recorded independently by clinicians and patients at screening and weeks 12 and 24. For each body region, a standardized scoring system (0 = none, 1 = mild, 2 = moderate, and 3 = severe) was assigned.28,29

Health-related quality of life was self-reported at week -1 and then at weeks 12 and 24 using the Short Form (SF)-36v2 Health Survey.30 The Multidimensional Body-Self Relations Questionnaire-Appearance Scales (MBSRQ-AS), a standardized measure of body image attitudes, assessed self-satisfaction with appearance and weight.31 Antiretroviral adherence was assessed using a standardized self-report form.32 Participants recorded whether they took all, most, about half, very few, or none of their pills during the preceding 7 days.

Statistical Analysis
The study had 80% power to detect an absolute difference of 25% in the proportion of participants with a clinically relevant change in FSTV between the immediate and deferred arms at 24 weeks using intention-to-treat analysis. We hypothesized that no more than 10% of deferred participants would show a clinically relevant improvement in soft tissue volume over 24 weeks, a more conservative estimate than earlier data.18 Analysis of the randomized comparison was performed when all randomized participants had completed 24 weeks of follow-up or had permanently withdrawn from follow-up. Baseline characteristics were summarized without formal comparison of the randomized groups.

All efficacy analyses compared the randomized treatment groups in terms of change from baseline to week 24 on an intention-to-treat basis and included all participants with baseline data and at least 1 follow-up assessment. Primary efficacy analyses adopted a last-value-carried-forward approach for participants lost to follow-up. Secondary analyses used only available data. Continuous endpoints were investigated using analysis of variance or nonparametric equivalents and binary endpoints assessed by _2 tests or logistic regression. All significance tests were 2-sided and not adjusted for multiple comparisons.

Serious adverse events, adverse events associated with PLA or leading to changes in ART, and all grade 3 or 4 clinical adverse events were summarized by treatment group. Events associated with PLA modification or cessation were summarized. An antiretroviral adherence score was calculated as described previously.33 Subgroup analyses were based on the following strata: age, patient-assessed facial lipoatrophy severity, baseline PI and thymidine nucleoside analogue use, and surgeon. Differences in outcome between the randomized treatment arms were assessed with tests of interaction between treatment and strata.

Univariate linear regression and multivariate linear regression were used to determine predictors of efficacy in PLA recipients, as assessed by change in facial volume at week 24, and predictors of safety, as determined by PLA cessation for toxicity or grade 3 or 4 adverse events. Post hoc analysis was performed to assess additional predictors of efficacy assessed by change in facial linear measurements at the maxilla and base of nasal septum levels at week 24. The following variables were assessed as predictors: baseline demographic characteristics, antiretroviral treatment, baseline CD4 cell count and HIV-1 viral load, smoking status, skin tanning type (Fitzpatrick scale),34 baseline limb fat mass and percent, and change in limb fat mass and percent at week 24 as assessed by DEXA. The final predictive model was determined using forward-stepwise regression. Variables with a univariate P value ≤0.1 were assessed in multivariate analysis.

RESULTS
Over a 6-week period during December 2005, and January 2006, 104 patients were screened and 101 participants randomized (see Fig. 2). One participant withdrew consent (patient choice) after randomization and was excluded from analysis. Most (92%) participants were men, 35 (35%) had AIDS, all were receiving ART, 65 were receiving a PI, and 14 were receiving a tNRTI (Table 1). Almost all (96%) participants rated their antiretroviral adherence as optimal (>95%). Self-assessed facial lipoatrophy was severe in 51 (26 immediate and 25 deferred) participants. Agreement between physical examination and self-assessed facial lipoatrophy severity was moderate (_ = 0.50). Mean baseline FSTV was 388 ± 71 cm3 in the immediate group and 393 ± 69 cm3 in the deferred group (see Table 1).

Safety bloods (complete blood cell count and coagulation screen) collected within 7 days of treatment initiation indicated that all immediate participants could proceed safely with PLA injections. Of the 50 immediate participants, 49 (98%) received 4 bilateral PLA treatments. One participant required only 1 treatment (2 vials) for adequate facial correction. Twenty-one antiretroviral drugs were stopped in 15 (15%) participants (6 immediate and 9 deferred). Most (62%) changes were within-class substitutions; 60% of these were for regimen simplification, with lamivudine (8 participants [5 immediate and 3 deferred]) and didanosine (3 participants [1 immediate and 2 deferred]) most commonly ceased. No participant ceased PI therapy or tNRTI therapy. There was no death or new AIDS-defining event. There was 1 screening protocol violation in the control arm. The patient had an HIV-1 RNA viral load in excess of 750,000 (5.88 log) copies/mL immediately before screening and commenced a new PI-containing regimen at week 6. No participant commenced any prohibited concomitant medication. Data for 100 participants (50 immediate and 50 deferred) were available for the intention-to-treat-analysis.

Efficacy: Objective Measures
PLA did not increase FSTV (Table 2). At week 24, the mean change in FSTV was 0 (95% confidence interval [CI]: -14 to 13) cm3 in the immediate group and -10 (95% CI: -22 to 1) cm3 in the deferred group, a difference of 10 (95% CI: -7 to 28) cm3 (P = 0.24). These represent changes of 0% and -3%, respectively, in FSTV. At week 24, 16% of the immediate group and 10% of the deferred group had a >10% increase in FSTV (P = 0.37). Treatment efficacy assessed by change in FSTV at week 24 did not differ significantly between any subgroup (data not shown).

The immediate group had a significantly greater mean change in tissue depth at the maxilla and base of nasal septum levels relative to the deferred group (2.2 [95% CI: 1.6 to 2.9] mm, P < 0.0001 and 1.0 [95% CI: 0.3 to 1.6] mm, P = 0.003, respectively). Facial thickness at the untreated orbit and mandibular levels was not increased by PLA. PLA therapy did not significantly affect any other objective body composition parameter, plasma viral load, or CD4 lymphocyte counts (see Table 2). Self-reported ART adherence was not different, with 96% of both groups reporting >95% adherence at week 24 (P = 1.0).

Analyses to investigate predictors of efficacy yielded inconsistent data. In multivariate analysis, significant predictors of a greater increase in FSTV at week 24 were prior AIDS (P = 0.002) and current PI therapy (P < 0.0001). Predictors of a greater increase in facial thickness at the maxillary level were Fitzpatrick skin types IV to VI (P = 0.035) and an improvement in limb fat from baseline to week 24 (P = 0.072). At the base of the nasal septum level, there was a trend for a greater increase in facial thickness to be associated with a limb fat increase between baseline and week 24 (P = 0.059).

Efficacy: Subjective Measures
Facial lipoatrophy severity was perceived as improved in 45 (90%) PLA recipients compared with 18% in the deferred group (P < 0.0001) at week 12 and in 84% and 18%, respectively, at week 24 (P < 0.0001). At week 12, clinicians perceived a reduction in severity in 90% of the immediate group, with no change or a worsening in 80% of deferred participants (P < 0.0001). At week 24, 86% of PLA recipients were perceived to have improved compared with 20% in the deferred group (P < 0.0001; Fig. 3). There was a significant association between self-assessed change in facial lipoatrophy severity and objectively assessed change in facial thickness at the maxilla level (P = 0.026) and a borderline association with change in thickness at the base of nasal septum (P = 0.079) (Fig. 4). There was no difference in any other clinician- or patient-assessed subjective measure of lipodystrophy or its severity at week 12 or 24.

At week 12, the mean change from baseline in the score for the Mental Health scale of the SF-36 Health Survey scale in PLA recipients was significantly different from the mean change in the deferred group (2.8 and -3.2, respectively; P = 0.026). At week 24, the mean change in scores for Social Functioning and Mental Health in the immediate group differed significantly from mean changes in the deferred group (P = 0.031 and P = 0.047, respectively; Fig. 5). Although the mean score for 5 SF-36 scales increased in the immediate group, the mean score for all 8 scales decreased in the deferred group. Additionally, the mean change in the Mental Health Component Summary score differed significantly in the immediate group relative to the deferred group (P = 0.048), but there was no difference in the Physical Component Summary score (P = 0.98) or in any of the scales associated with physical functioning. Body self-image assessed using the MBSRQ-AS showed that the mean change in appearance evaluation and body areas satisfaction subscale scores in the immediate group was significantly different from scores in the deferred group (0.19 and -0.03, P = 0.040 and 0.29 and -0.12, P < 0.0001, respectively) at week 12 and at week 24 (0.15 and -0.15, P = 0.010 and 0.19 and -0.11, P = 0.0004, respectively).

Safety/Tolerability
Forty-eight (96%) PLA recipients experienced at least 1 procedure/product-related adverse event, with pain/discomfort (76%), localized edema (64%), and erythema (53%) reported most commonly (Table 3). Most events were grade 1 or 2 and were of short duration (median = 2 [interquartile range [IQR]: 1 to 3] days). No treatment was delayed or terminated for adverse events, surgical or clinical discretion, or patient wish. At week 24, there were 4 palpable and 1 visible ongoing subcutaneous noninflammatory nodules and 1 papule at the injection site in 6 participants (12%). These events were noted at the injection site 5 to 19 weeks after the first injection. Five serious adverse events were reported in 4 participants: 3 events (epidural abscess, surgery to resect renal tumor, and hospitalization for lower lobe pneumonia) in the immediate group (2 participants) and 2 events (surgery for perianal abscess and acute renal retention) in the deferred group (2 participants). None of these events was associated with PLA. Additionally, no other grade 4 event was considered definitely, probably, or possibly related to PLA.

CATIE News – After LGV treatment—STIs return

 

In 2003, reports emerged from the Netherlands about a strain of Chlamydia that causes a disease called LGV—lymphogranuloma venereum.

 

Before this, LGV was uncommon in high-income countries. But the initial report from the Netherlands was followed by similar cases in other Western European countries and later Australia, the United States and Canada. Nearly all of the cases have been among men who had sex with men (MSM), many of whom also had HIV.

 

If left untreated, LGV can cause serious, painful complications because of scarring inside the penis, scrotum and rectum. LGV can also damage lymph nodes and vessels. The sores caused by LGV in the rectum can also allow other germs—such as those that cause hepatitis, syphilis and gonorrhea—to invade the body.

 

The current outbreak of LGV in high-income countries seems to be spread by unprotected anal sex. Further details about LGV transmission appear later in this bulletin.

 

Signs and symptoms
Initially, a small, painless sore on the genitals may appear within 3 to 30 days after exposure to LGV. This quickly disappears. Later, the germs that cause LGV spread from the genitals to nearby lymph nodes, causing some to swell painfully.

 

In other cases, persistent rectal ulcers and inflammation can occur. This can lead to rectal bleeding and painful bowel movements, constipation and rectal discharge.

 

In addition to these symptoms, LGV germs can travel beyond the genitals, causing the following:

 

* headache
* lack of energy
* fever
weight loss

 

Because symptoms of LGV can mimic those of inflammatory bowel disease, some cases of LGV have been misdiagnosed. The Public Health Agency of Canada (PHAC) notes that routine tests for Chlamydia may come back positive in people with LGV, but these tests do not specifically identify LGV-causing germs.

 

The agency advises that doctors need to request that specific testing for LGV be done on the samples they send. The availability of this type of testing varies across Canada; physicians can contact their local public health unit or provincial laboratory to find out more.

 

Treatment
To help wipe out LGV-causing germs, the recommended first-line treatment is a three-week course of the antibiotic doxycycline 100 mg twice daily. An alternative antibiotic is erythromycin 500 mg four times daily, also for three weeks. Some doctors have used another antibiotic, azithromycin (Zithromax), in cases where doxycycline could not be taken. However, there is no consensus as to the correct dose, schedule and length of therapy for the use of azithromycin against LGV.

 

Focus on infection
To find out exactly how LGV may have been transmitted, several research teams have conducted intensive investigation and questioning of people with LGV. Here are the routes of transmission:

 

* unprotected anal sex
* unprotected insertion of fingers or hands (fisting) into the anus
* sharing of sex toys

 

Also note the following:

 

* HIV positive men seem to be very susceptible to LGV, perhaps because immune defenses in the gut are dysfunctional.
* The use of HAART or having relatively high CD4+ cell counts does not provide protection from LGV.

 

Re-infection
Now researchers in Rotterdam, the Netherlands, have reported some disturbing news:

 

* Some men who have recovered from LGV have been engaging in unprotected intercourse again and catching new sexually transmitted infections (STIs).

 

Study details and results
The Dutch study team reviewed medical records of men who were treated for LGV between 2002 and 2005. The purpose of the study was to assess STIs that may have occurred after treatment for LGV.

 

The team found that out of 26 men who had recovered from LGV, 17 (65%) acquired a new STI shortly after treatment for LGV. Most of these men were already co-infected with HIV and hepatitis B. The most common STI that they later acquired was syphilis.

 

The Dutch team had hoped that since LGV was a serious illness these men would have begun to have protected intercourse after their LGV diagnosis. However, after being treated for LGV some of the men had new rectal infections with other germs, including syphilis.

 

The Dutch doctors stated that these new STIs suggest that “health education efforts need to be stepped up vigorously.” Australian doctors also treating a cluster of LGV cases in Sydney noted that “counselling about healthy sexual practices is [important in the fight against STIs].” Hopefully, reports of STIs in people recovering from LGV are not a harbinger of events to come in Canada and other high-income countries.

 

LGV in Canada
According to PHAC, there have been 88 cases of LGV reported to that agency since 2001. Most of the Canadian cases of LGV occurred after January 2005 and all involved unprotected sex between men who generally did not appear to acquire the infection overseas. Risk behaviours included the following:

 

* unprotected anal sex
* fisting
* sharing of sex toys
* rectal use of crystal meth (crystal methamphetamine)

 

Canadian LGV cases have commonly reported co-infection with the following:

 

* HIV
* hepatitis C virus
* syphilis

 

Recently, reports of LGV in Canada appear to be declining, a trend that will hopefully continue.

 

—Sean R. Hosein

 

REFERENCES:

 

1. Tinmouth J, Rachlis A, Wesson T, et al. Lymphogranuloma venereum in North America: case reports and an update for gastroenterologists. Clinical Gastroenterology and Hepatology 2006 Apr;4(4):469-73.

 

2. Hamill M, Benn P, Carder C, et al. The clinical manifestations of anorectal infection with lymphogranuloma venereum (LGV) versus non-LGV strains of Chlamydia trachomatis: a case-control study in homosexual men. International Journal of STD and AIDS 2007 Jul;18(7):472-5.

 

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NATAP http://natap.org/
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Press release - HillaryClinton.com  11/27/2007

Clinton Announces Plan to Fight HIV/AIDS At Home And Abroad
Will Double Research Funding & Support Evidence-Based Prevention Programs

The Clinton campaign unveiled its plan to fight the HIV/AIDS epidemic in the U.S. and around the world. The comprehensive approach addresses the multiple challenges that HIV/AIDS has presented for over 25 years and includes investments for increased research, prevention and education, and access to treatment and other services. Hillary's plan would especially help groups in the U.S. that have seen HIV infection rates rise over the past several years, including African Americans and gay men, and address the continued risk in Latino communities and among women. In addition, Clinton has pledged to increase funding for the global HIV/AIDS fight to at least $50 billion by 2013.

"In many ways, our fight against HIV/AIDS is at a crossroads. While we have made progress in education and developing medicine that keeps those living with HIV/AIDS healthier, we need to be vigilant in ensuring that people are getting the information and care they need,” said Clinton. “I believe with leadership and smart investments we can significantly reduce the number of new infections, develop treatments that turn HIV/AIDS into a chronic but manageable condition, and expand toward an eventual vaccine."

On the domestic front, Clinton proposes doubling the HIV/AIDS research budget within the National Institutes of Health (NIH) to $5.2 billion annually, including the U.S. contribution towards finding a vaccine. Clinton's American Health Choices Plan will ensure that all Americans living with HIV/AIDS have access to care. Hillary will end the Bush administration's abstinence-only prevention policy, and instead, fund evidence-based HIV/AIDS prevention programs including, but not limited to, abstinence education as part of a comprehensive prevention message.

Hillary will address the disproportionate burden of HIV/AIDS among minority communities. African Americans account for almost 50% of new infections and Hillary will partner with stakeholders in the community to reverse this trend immediately. She is also concerned about the high rates of infection in the Latino community and will take action to improve prevention among Hispanics. Hillary will increase funding for the Minority AIDS Initiative and support the prevention and treatment efforts of minority-run community based organizations. Her plan also increases federal funding for substance abuse treatment, which often leads to high-risk behavior that can lead to infection. By taking steps to crack down on substance abuse and help users seek treatment, the chance that people will contract HIV can be greatly reduced.

Hillary is taking a bold stand to fight HIV/AIDS globally as well. She has committed to providing at least $50 billion over five years to combat HIV/AIDS around the world. This commitment will establish the U.S. as a leader in galvanizing the global community around meeting the Millennium Development Goal of halting and beginning to reverse the spread of HIV and other diseases by 2015. She will lead the world in achieving universal access to treatment by doubling the number of people that the U.S. supports with treatment. The Clinton plan will increase the number of health workers in training or in place in Africa by at least one million over a decade and ensure access to medications for all.

HILLARY CLINTON'S PLAN TO FIGHT HIV/AIDS IN THE U.S. AND AROUND THE WORLD

Today, Hillary Clinton unveiled her plan to combat HIV/AIDS globally through U.S. leadership and effective investments in research, prevention, and treatment. There are 33 million people living with HIV/AIDS around the world. Every day, about 6,800 people become newly infected and 5,700 die because of AIDS. Here in the U.S., while we have made tremendous strides in combating HIV/AIDS, about 40,000 people are newly diagnosed with HIV each year - an estimate which is expected to increase. More than 16,000 Americans die from AIDS annually and AIDS is the leading cause of death among African-American women aged 25-34.

AIDS has had a devastating impact on the continent of Africa, where more than two-thirds of all people with HIV/AIDS live, more than three-quarters of AIDS-related deaths occur and where the epidemic has orphaned 11 million children.

With a coordinated and comprehensive effort, Hillary knows we can significantly reduce the number of new infections annually and help provide coordinated care and treatment to the more than one million Americans currently living with HIV/AIDS in the U.S. and the millions living with HIV/AIDS around the world. As President, Hillary will:

Fight HIV/AIDS in the U.S. by:

    * Developing and Implementing a Comprehensive National AIDS Strategy;
    * Guaranteeing Health Insurance for Individuals Living with HIV/AIDS;
    * Doubling the U.S. Contribution Towards Researching a Vaccine for HIV/AIDS and Increasing Commitments to Research;
    * Ensuring Access to Care for All Americans Living with HIV;
    * Increasing Funding for Evidence-Based HIV/AIDS Prevention;
    * Addressing High Risk Behaviors that Often Lead to HIV/AIDS;
    * Improving Opportunities for Substance Abuse Treatment;
    * Providing Housing Opportunities and Supportive Services for People with AIDS;
    * Increasing Funding for the Ryan White CARE Act; and
    * Halting and Reversing the Burden of AIDS Among African-Americans and Latinos.

Fight HIV/AIDS Globally by:

    * Providing at Least $50 Billion for Global HIV/AIDS by 2013;
    * Ensuring Universal Access to Treatment and Care;
    * Committing to Access to Medications for All;
    * Expanding Prevention Efforts and Targeted Outreach;
    * Championing Universal Basic Education as a "Social Vaccine" to Combat HIV/AIDS;
    * Increasing Flexibility and Improving Accountability in Use of HIV/AIDS Funds;
    * Addressing the Disproportionate Impact of HIV Among Women; and
    * Helping Children Gain Access to Treatment and Care.


This plan builds on Hillary's long history of working to address the HIV/AIDS epidemic. As Senator, Hillary has introduced legislation to expand access to treatment for low-income individuals living with HIV; pushed to make scientific, evidence-based prevention programs more available to youth; sought to increase coordination in combating global AIDS; championed legislation to provide universal basic education that would help prevent the spread of AIDS, and consistently supported increased funding for federal efforts against the epidemic both in the U.S. and around the world.

HILLARY CLINTON'S PLAN TO FIGHT HIV/AIDS IN THE U.S.

As President, Hillary Clinton will continue her commitment to providing care and support for people living with HIV, as well as stopping the spread of the virus by:

Developing and Implementing a Comprehensive National AIDS Strategy - Federal efforts to tackle HIV/AIDS are diffuse and uncoordinated today, failing to maximize coordination among agencies providing treatment, support and care, and limiting our efforts to engage in effective prevention. Hillary will tie all of the federal efforts together into a single comprehensive national strategy. She will bring together federal agencies, such as the Centers for Disease Control and Prevention, the Health Resources and Services Administration, and the Centers for Medicare and Medicaid Services, state and local governments, community-based organizations, providers, academic experts, and Americans living with HIV, among others, to devise a plan to better coordinate the overall response to this epidemic in the U.S., with the goals of significantly reducing the number of new infections, particularly among populations with increases in infection rates, improving the health of people living with HIV, and reducing disparities in care. This plan will include measurable goals, targets, and timelines for increasing evidence-based prevention and expanding effective treatment interventions, so that we can monitor and evaluate our efforts, expand what is working, and correct what is not. This single, comprehensive strategy will allow for better cooperation and more efficient and effective allocation of resources, so that we can stop and reverse the increases in HIV infection among vulnerable populations.

Guaranteeing Health Insurance for Individuals Living with HIV/AIDS - Hillary has proposed the American Health Choices Plan, which ensures that every American will have access to affordable, quality health insurance. Under her plan, insurers will not be able to deny coverage based on preexisting conditions, such as HIV infection. Safety net care options, like Medicaid, will be strengthened, while individuals will be able to choose from an array of plans with benefits at least as good as the typical plan offered to Members of Congress, which includes mental health parity. Health care will be made affordable through the provision of a premium affordability tax credit, which will be designed to ensure that health care premiums never exceed a reasonable portion of a person's income. With the American Health Choices Plan, individuals with HIV/AIDS will have access to chronic care management, helping ensure that their providers are coordinating care for the best outcomes.

Doubling the U.S. Contribution Towards Researching a Vaccine for HIV/AIDS and Increasing Commitments to Research - Hillary believes we should never stop working to achieve the end goal of a cure for AIDS, and recent setbacks in vaccine trials do not mitigate the need to develop a vaccine to combat this disease. During the 1990s, new drugs helped people with HIV and AIDS live longer, healthier lives. In addition to increasing access to these drugs, the federal government must also research new treatments to simplify regimens, increase adherence, and address issues of drug resistance. We must also focus on funding for prevention - whether it is through efforts to fund microbicide research, or efforts to evaluate the best behavioral health strategies for preventing HIV and AIDS. In order to achieve these goals, Hillary would increase our investments in HIV/AIDS research at the National Institutes of Health to $5.2 billion annually, and ensure that researchers in all areas have the resources necessary to continue and expand their valuable efforts.

Ensuring Access to Care for All Americans Living with HIV - Hillary will extend Medicaid eligibility to low-income Americans living with HIV by the end of her first year in office. Today, too many low-income Americans with HIV have to wait until they become sick in order to receive health care through Medicaid. Delaying care in this manner hurts those who could have avoided illness through preventive care and treatment, and increases the costs associated with their care over the long-term. Hillary will change the Medicaid rules so that early treatment and intervention is guaranteed. This proposal builds on Hillary's record as the lead Democratic sponsor of the Early Treatment for HIV/AIDS Act, and helps to strengthen the affordable options available for those living with HIV as part of her America's Health Choices Plan.

Increasing Funding for Evidence-Based Prevention Efforts - As President, Hillary will work to give individuals the tools needed to protect themselves against HIV by supporting proven strategies and targeting those efforts to the populations most vulnerable to HIV infection. Hillary supports giving young people age-appropriate information about HIV/AIDS and how to protect themselves against the disease, including by delaying sexual activity. But she rejects the Bush Administration approach of investing exclusively in abstinence-only sex education. She supports federal funding for needle exchange programs. And she will work to target culturally competent prevention efforts towards vulnerable populations that account for a disproportionate number of new infections. In addition, she will ensure that women, who account for more than one-quarter of all new HIV/AIDS infections in the U.S., have the knowledge and tools necessary to protect themselves against HIV.

Addressing High Risk Behaviors That Often Lead to HIV/AIDS - Hillary will work to halt and reverse the recent increase in infection rates among gay men, young people, and people of color. In addition, Hillary will seek to address the factors that contribute to high risk behavior, such as the use of drugs like crystal meth, which is impacting both rural and urban areas, and the use of which is on the rise in the gay community. Hillary was a proud co-sponsor of the Combat Meth Act of 2005, which was signed into law on March 9, 2006. This law tightens restrictions on how pseudoephedrine is sold to ensure that it is not being trafficked, and provides resources for prevention, education, and treatment. As President, Hillary will work to see that this law is implemented effectively.

Improving Opportunities for Substance Abuse Treatment Services - Providing federal funding for needle exchange programs will help increase referrals and entry into treatment programs and reduce overall HIV incidence, but there is much more we can do to address the connections between substance use and HIV infection. Hillary will expand available treatment services and provide additional federal assistance for such services by increasing funding for SAMHSA, the Substance Abuse and Mental Health Services Administration. In a 2006 SAMHSA study more than 23 million Americans were identified as needing specialty treatment for substance or alcohol abuse, yet only about 10% of them accessed such services. A major barrier to receiving such services is the cost of treatment.

Providing Housing Opportunities and Supportive Services for People with AIDS - As many as half of all people living with HIV/AIDS will need housing assistance at some point in their illness. For many of those, short-term assistance with rent, mortgage or utility costs alone will provide the necessary support to remain healthy and in stable housing. But for others, more intensive supportive services are needed. Hillary will increase funding for the Housing Opportunities for People with AIDS (HOPWA) program to serve about 90,000 households. In addition, Hillary recognizes the importance of supportive services for individuals living with HIV and their families. With stable housing and supportive services, individuals are more likely to be able to access comprehensive health care and adhere to HIV/AIDS treatments, improving their medical outcomes and reducing health care costs.

Increasing Funding for the Ryan White CARE Act - The Ryan White CARE Act is an important mechanism through which to deliver treatment and supportive services to individuals living with HIV and AIDS. As President, Hillary will support increasing Ryan White funding, especially in underserved areas and areas where the epidemic is growing, and working to make sure the increases are coordinated with other federal programs. She will also work to increase flexibility of funding to be used for supportive services - such as nutrition assistance and case management - that increase treatment adherence and improve the health and well-being of Americans living with AIDS.

Halting and Reversing the Burden of AIDS Among African-Americans and Latinos - Hillary will increase funding for the Minority AIDS Initiative, and work to ensure that it helps to foster and support the prevention and treatment efforts of minority-run community based organizations. This effort is particularly important in the African American community, as African Americans in the U.S. account for approximately 13% of the population, yet make up almost half of the new HIV/AIDS diagnoses. Hillary will work to end the disproportionate impact of AIDS on this community and seek to halt the growth of HIV in other minority communities as well. In addition, she will seek to increase cooperation with the clergy and other religious leaders in the black and Hispanic communities, to determine how churches can play a role in reducing the number of new infections. Finally, she will work to reduce and eliminate racial and ethnic disparities throughout our entire health care system, to ensure that African Americans and Latinos living with HIV and AIDS have access to quality care and treatment.

HILLARY CLINTON'S PLAN TO FIGHT HIV/AIDS WORLDWIDE

As First Lady, Hillary Clinton saw the impact of HIV and AIDS in her travels around the globe. As Senator from New York, she has worked to secure funding and improve coordination for global AIDS programs. As President, she will continue our efforts to secure universal access for treatment, prevention, and care by focusing on the following:

Providing at Least $50 Billion for Global HIV/AIDS by 2013 - Hillary has a long record of advocating for funding for both U.S. and multilateral efforts to fight HIV/AIDS around the world. While we have made important progress on funding over the past decade, Hillary believes that we must go beyond the President's request to flat-line global HIV/AIDS funding over the next 5 years. She is currently fighting in the Senate to reauthorize and improve PEPFAR - the President's Emergency Plan For AIDS Relief. And as President, Hillary will commit at least $50 billion for global HIV/AIDS efforts by 2013. This investment will allow the U.S. to increase our commitment to the Global Fund to Fight AIDS, Tuberculosis and Malaria, which leverages additional donor commitments to support coordinated national approaches to fighting disease. It will establish the U.S. as a leader in galvanizing the global community around meeting the Millennium Development Goal of halting and beginning to reverse the spread of HIV and other diseases by 2015.

Ensuring Universal Access to Treatment and Care - With increased funding, Hillary Clinton will expand access to treatment in developing countries. The U.S. will take the lead in ensuring that we reach universal access to medications by doubling the number of people that the U.S. supports with treatment over the next several years. Hillary will also invest in building the health infrastructure of developing countries that is critical to achieving effective treatment and prevention of HIV/AIDS and other diseases. This will include working with international partners to increase the number of health workers in place or in training in Africa by at least one million over the next several years, improve the self-sufficiency of local health networks, and reduce global disparities in care.

Committing to Access to Medications for All - Hillary understands that in order to meet our goals for universal access to treatment, we must make available the life-extending medications we have in the U.S. to resource-poor countries. The World Health Organization estimates that 10 million lives could be saved each year by improving access to medicines already in existence. As President, Hillary will ensure the U.S. lives up to its Doha Declaration commitments and allow countries to access the treatments necessary to address public health crises like HIV/AIDS. She will support trade policies that protect and expand poor countries' right to affordable, quality-assured generic drugs for important health needs. As President, she will also work with institutions that receive federal funding to ensure that drugs developed with taxpayer resources are made available off-patent in developing countries.

Expanding Prevention Efforts and Targeted Outreach - Hillary wants to maximize the impact of new U.S. funding in prevention efforts at the local level. She believes that effective prevention models should be tailored to the needs of communities, without requirements that limit the ability to provide accurate information and relevant comprehensive services to as many individuals as possible. To that end, she supports striking the current requirement that 33% of prevention funding be spent on abstinence-only programs, to ensure that prevention efforts can be tailored to local needs and populations most at-risk. She also supports using U.S. funding to support proven harm reduction efforts - including needle exchange - to help hard-to-reach populations, and will continue to support new evidence-based prevention methods as additional scientific research helps us understand how to best address this epidemic. Hillary will also work to support efforts to reduce stigma and improve outreach and education around testing. When people get tested, and they discover they are positive, we can help them access treatment, medical care, and information about the virus before they become sick. If people get tested and they are negative, counselors can help them understand how they can avoid infection.

Championing Universal Basic Education as a "Social Vaccine" to Combat HIV/AIDS - Hillary is the original Senate sponsor of the Education For All Act, which calls for a dramatic increase in US funding and leadership in achieving universal basic education. In addition to reducing poverty and improving child and maternal health, education is a key form of prevention - a "social vaccine"- against the spread of HIV/AIDS. Compared to peers who are out of school, girls enrolled in secondary education are more likely to resist early marriage and remain abstinent, while also being five times more likely to know the basic facts of prevention and three times less likely to contract HIV/AIDS. With strong peer support programs, life skills training, and prevention curricula that address HIV/AIDS, gender-based violence and other health concerns, education can be even more effective in combating HIV/AIDS.

Increasing Flexibility and Improving Accountability in Use of Funds - Hillary Clinton wants to work with both donors and recipient governments to ensure that U.S. investments are made as effectively as possible. Donors must work to improve coordination and reduce the burden placed on poor country ministries of multiple, overlapping and sometimes conflicting reporting requirements. Developing countries must work with donors to identify the impact of the epidemic on a localized basis and help target prevention and treatment efforts to vulnerable populations that are often overlooked, including orphans, displaced persons and individuals who have been trafficked. Doing so will allow the U.S., at the country level, to better identify needs, eliminate duplication, and establish monitoring and evaluation systems to better track funding. In addition, Hillary will increase funding for operations research to identify and replicate best practices in prevention, care and treatment. Finally, Hillary will work to improve outreach and coordination with nonprofit organizations, businesses, faith-based groups, people living with HIV and AIDS and other nongovernmental entities to ensure that civil society is engaged and active in efforts to prevent and treat HIV/AIDS.

Addressing the Disproportionate Impact of HIV Among Women - Worldwide, adult women account for almost half of all new infections, and in certain areas, like sub-Saharan Africa, women account for more than 60% of those living with HIV. As President, Hillary Clinton will work to reduce infections among women, improve their access to care and treatment, and give them the tools needed to protect themselves against infection. She will require our government to develop a comprehensive plan to address the needs of girls and women and integrate these needs into our efforts to address HIV/AIDS. This plan will identify and address factors, such as gender-based violence and economic insecurity, which are linked with increased vulnerability to HIV. It will also work to improve services for women, in order to integrate HIV and AIDS care into existing health service delivery, including sexual and reproductive health services and family planning. In addition to working to ensure that the health needs of women are addressed in our global AIDS policies, Hillary Clinton will also improve access to overall women's health services that help provide treatment, care and education. She would restore U.S. funding for UNFPA, which provides vital reproductive health services to women around the world, and rescind the Global Gag Rule, which prevents U.S. funding from assisting nongovernmental organizations in other countries that provide information about or access to abortion services.

Helping Children Gain Access to Treatment and Care - The majority of children living with HIV worldwide die before the age of three. As First Lady and Senator, Hillary worked to increase the number of medications specifically manufactured for children, including those that would treat AIDS. As President, she will work to ensure that the gains we have made in increasing treatment options are extended to children around the world. As she moves to improve needs assessments and expand treatment across the lifespan, she will work to ensure that children's needs are included in strategies for fighting AIDS, including plans for the care and treatment of orphans and other vulnerable children who have lost their families to the AIDS epidemic.