As-Needed Vs Immediate Etoposide Chemotherapy in Combination With Antiretroviral Therapy for Mild-to-Moderate AIDS-Associated Kaposi Sarcoma in Resource-Limited Settings: A5264/AMC-067 Randomized Clinical Trial.

Background: Mild-to-moderate AIDS-associated Kaposi sarcoma (KS) often responds to antiretroviral therapy (ART) alone; the role of chemotherapy is unclear. We assessed the impact of immediate vs as-needed oral etoposide (ET) among human immunodeficiency virus (HIV)-infected individuals with mild-to-moderate KS initiating ART. Methods: Chemotherapy-naive, HIV type 1-infected adults with mild-to-moderate KS initiating ART in Africa and South America were randomized to ART (tenofovir/emtricitabine/efavirenz) alone (chemotherapy "as-needed" arm) vs ART plus up to 8 cycles of oral ET (immediate arm). Participants with KS progression on ART alone received ET as part of the as-needed strategy. Primary outcome was ordinal as follows: failure, stable, and response at 48 weeks. Secondary outcomes included time to initial KS progression, KS-associated immune reconstitution inflammatory syndrome (KS-IRIS), and KS response. Results: Of 190 randomized participants (as-needed = 94, immediate = 96), the majority were men (71%) and African (93%). Failure (53.8% vs 56.6%), stable (16.3% vs 10.8%), and response (30% vs 32.5%) did not differ between arms (as-needed vs immediate) among those with week 48 data potential (N = 163, P = .91). Time to KS progression (P = .021), KS-IRIS (P = .003), and KS response (P = .003) favored the immediate arm. Twenty-five participants died (13%). Mortality, adverse events, CD4+ T-cell changes, and HIV RNA suppression were similar at 48 weeks. Conclusions: Among HIV-infected adults with mild-to-moderate KS, immediate ET provided early, nondurable clinical benefits. By 48 weeks, no clinical benefit was observed compared to use of ET as needed. Mortality was high and tumor response was low. Clinical Trials Registration: NCT01352117.

Hearing-aid safety: a comparison of estimated threshold shifts for gains recommended by NAL-NL2 and DSL m[i/o] prescriptions for children.

OBJECTIVE: To investigate the predicted threshold shift associated with the use of nonlinear hearing aids fitted to the NAL-NL2 or the DSL m[i/o] prescription for children with the same audiograms. For medium and high input levels, we asked: (1) How does predicted asymptotic threshold shifts (ATS) differ according to the choice of prescription? (2) How does predicted ATS vary with hearing level for gains prescribed by the two prescriptions? DESIGN: A mathematical model consisting of the modified power law combined with equations for predicting temporary threshold shift (Macrae, 1994b) was used to predict ATS. STUDY SAMPLE: Predicted threshold shift were determined for 57 audiograms at medium and high input levels. RESULTS: For the 57 audiograms, DSL m[i/o] gains for high input levels were associated with increased risk relative to NAL-NL2. The variation of ATS with hearing level suggests that NAL-NL2 gains became unsafe when hearing loss > 90 dB HL. The gains prescribed by DSL m[i/o] became unsafe when hearing loss > 80 dB HL at a medium input level, and > 70 dB HL at a high input level. CONCLUSION: There is a risk of damage to hearing for children using nonlinear amplification. Vigilant checking for threshold shift is recommended.

Acute retroviral syndrome is associated with lower CD4 + T cell nadir and delayed viral suppression, which are blunted by immediate antiretroviral therapy initiation.

OBJECTIVES: To describe the prevalence of acute retroviral syndrome (ARS) and associated findings during primary HIV, and explore the relationship of ARS to clinical, virological, and immunological outcomes within a longitudinal screen, retest and treat study that minimized ascertainment bias. DESIGN: We evaluated ARS symptoms and signs among 216 persons with acute and early incident HIV within the Sabes study of timing of antiretroviral therapy (ART) initiation during primary HIV in Peru. METHODS: We evaluated patient reported symptoms and signs during primary HIV and used logistic regression and generalized linear models to evaluate associations with CD4 + and CD8 + T cell counts, HIV viral load, and a panel of 23 soluble markers of immune activation. RESULTS: Sixty-one percent of participants had at least one ARS finding and 35% had at least 3. More ARS findings were reported in those enrolled within a month of estimated date of detectable infection (EDDI). Having more ARS signs/symptoms was associated with increased risk of CD4 + cell decrease below 350 cells/ml within the first 24 weeks, failure to suppress HIV viral load, and was most strongly associated with elevated IP-10. Immediate ART blunted effects on symptoms, CD4 + cell count and viral load, as associations were strongest in the arm that started ART after 24 weeks. Detrimental associations of ARS with CD4 + counts, and CD4 + /CD8 + ratio were not maintained at 2 or 4 years. CONCLUSIONS: ARS has marked associations with short-term immunologic function and virologic suppression, which were mitigated in participants randomized to initiate ART immediately during primary infection.

Validity of the National Acoustic Laboratories procedure for determining percentage loss of hearing.

OBJECTIVE: To evaluate the validity of the National Acoustic Laboratories procedure for determining percentage loss of hearing as a measure of hearing disability. DESIGN: The percentage hearing losses of war veterans who had hearing ranging from normal to profound deafness were determined and compared with their scores on two hearing questionnaires. STUDY SAMPLE: A self-report hearing questionnaire was completed by 282 war veterans and 154 of those veterans were given the hearing measurement scale in the form of a structured interview. RESULTS: A percentage loss of hearing of 0 agreed well with the questionnaire scores representing the limit of normal hearing, and a percentage loss of hearing of 100 agreed well with the questionnaire scores representing total loss of hearing. Percentage loss of hearing accounted for 83% of the variance in scores on the hearing questionnaire and 81% of the variance in scores on the hearing measurement scale. CONCLUSION: The National Acoustic Laboratories procedure for determining percentage loss of hearing provides a valid measure of hearing disability.

Patterns and correlates of PrEP drug detection among MSM and transgender women in the Global iPrEx Study.

BACKGROUND: Adherence to pre-exposure prophylaxis (PrEP) is critical for efficacy. Antiretroviral concentrations are an objective measure of PrEP use and correlate with efficacy. Understanding patterns and correlates of drug detection can identify populations at risk for nonadherence and inform design of PrEP adherence interventions. METHODS: Blood antiretroviral concentrations were assessed among active arm participants in iPrEx, a randomized placebo-controlled trial of emtricitabine/tenofovir in men who have sex with men and transgender women in 6 countries. We evaluated rates and correlates of drug detection among a random sample of 470 participants at week 8 and a longitudinal cohort of 303 participants through 72 weeks of follow-up. RESULTS: Overall, 55% of participants (95% confidence interval: 49 to 60) tested at week 8 had drug detected. Drug detection was associated with older age and varied by study site. In longitudinal analysis, 31% never had drug detected, 30% always had drug detected, and 39% had an inconsistent pattern. Overall detection rates declined over time. Drug detection at some or all visits was associated with older age, indices of sexual risk, including condomless receptive anal sex, and responding "don't know" to a question about belief of PrEP efficacy (0-10 scale). CONCLUSIONS: Distinct patterns of study product use were identified, with a significant proportion demonstrating no drug detection at any visit. Research literacy may explain greater drug detection among populations having greater research experience, such as older men who have sex with men in the United States. Greater drug detection among those reporting highest risk sexual practices is expected to increase the impact and cost-effectiveness of PrEP.