Dataset Information

Reduced bacterial skin infections in HIV-infected African children randomized to long-term cotrimoxazole prophylaxis.

ABSTRACT:

Objective

To evaluate whether cotrimoxazole prophylaxis prevents common skin conditions in HIV-infected children.

Design

Open-label randomized controlled trial of continuing versus stopping daily cotrimoxazole (post-hoc analysis).

Setting

Three sites in Uganda and one in Zimbabwe.

Participants

A total of 758 children aged more than 3 years receiving antiretroviral therapy (ART) for more than 96 weeks in the ARROW trial were randomized to stop (n = 382) or continue (n = 376) cotrimoxazole after median (interquartile range) 2.1(1.8, 2.2) years on ART.

Intervention

Continuing versus stopping daily cotrimoxazole.

Main outcome measures

Nurses screened for signs/symptoms at 6-week visits. This was a secondary analysis of ARROW trial data, with skin complaints categorized blind to randomization as bacterial, fungal, or viral infections; dermatitis; pruritic papular eruptions (PPEs); or others (blisters, desquamation, ulcers, and urticaria). Proportions ever reporting each skin complaint were compared across randomized groups using logistic regression.

Results

At randomization, median (interquartile range) age was 7 (4, 11) years and CD4 was 33% (26, 39); 73% had WHO stage 3/4 disease. Fewer children continuing cotrimoxazole reported bacterial skin infections over median 2 years follow-up (15 versus 33%, respectively; P < 0.001), with similar trends for PPE (P = 0.06) and other skin complaints (P = 0.11), but not for fungal (P = 0.45) or viral (P = 0.23) infections or dermatitis (P = 1.0). Bacterial skin infections were also reported at significantly fewer clinic visits (1.2 versus 3.0%, P < 0.001). Independent of cotrimoxazole, bacterial skin infections were more common in children aged 6-8 years, with current CD4 cell count less than 500 cells/μl, WHO stage 3/4, less time on ART, and lower socio-economic status.

Conclusion

Long-term cotrimoxazole prophylaxis reduces common skin complaints, highlighting an additional benefit for long-term prophylaxis in sub-Saharan Africa.

SUBMITTER: Prendergast AJ

PROVIDER: S-EPMC5976221 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Reduced bacterial skin infections in HIV-infected African children randomized to long-term cotrimoxazole prophylaxis.

Prendergast Andrew J AJ Bwakura-Dangarembizi Mutsa M Mugyenyi Peter P Lutaakome Joseph J Kekitiinwa Adeodata A Thomason Margaret J MJ Gibb Diana M DM Walker A Sarah AS

AIDS (London, England) 20161101 18

<h4>Objective</h4>To evaluate whether cotrimoxazole prophylaxis prevents common skin conditions in HIV-infected children.<h4>Design</h4>Open-label randomized controlled trial of continuing versus stopping daily cotrimoxazole (post-hoc analysis).<h4>Setting</h4>Three sites in Uganda and one in Zimbabwe.<h4>Participants</h4>A total of 758 children aged more than 3 years receiving antiretroviral therapy (ART) for more than 96 weeks in the ARROW trial were randomized to stop (n = 382) or continue (n ...[more]

PMID: 27662556

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Project description:BackgroundCotrimoxazole (CTX) prophylaxis is recommended by the World Health Organization (WHO) for HIV-1-infected individuals in settings with high infectious disease prevalence. The WHO 2006 guidelines were developed prior to the scale-up of antiretroviral therapy (ART). The threshold for CTX discontinuation following ART is undefined in resource-limited settings.Methods and findingsBetween 1 February 2012 and 30 September 2013, we conducted an unblinded non-inferiority randomized controlled trial of CTX prophylaxis cessation versus continuation among HIV-1-infected adults on ART for ≥ 18 mo with CD4 count > 350 cells/mm3 in a malaria-endemic region in Kenya. Participants were randomized and followed up at 3-mo intervals for 12 mo. The primary endpoint was a composite of morbidity (malaria, pneumonia, and diarrhea) and mortality. Incidence rate ratios (IRRs) were estimated using Poisson regression. Among 538 ART-treated adults screened, 500 were enrolled and randomized, 250 per arm. Median age was 40 y, 361 (72%) were women, and 442 (88%) reported insecticide-treated bednet use. Combined morbidity/mortality was significantly higher in the CTX discontinuation arm (IRR = 2.27, 95% CI 1.52-3.38; p < 0.001), driven by malaria morbidity. There were 34 cases of malaria, with 33 in the CTX discontinuation arm (IRR = 33.02, 95% CI 4.52-241.02; p = 0.001). Diarrhea and pneumonia rates did not differ significantly between arms (IRR = 1.36, 95% CI 0.82-2.27, and IRR = 1.43, 95% CI 0.54-3.75, respectively). Study limitations include a lack of placebo and a lower incidence of morbidity events than expected.ConclusionsCTX discontinuation among ART-treated, immune-reconstituted adults in a malaria-endemic region resulted in increased incidence of malaria but not pneumonia or diarrhea. Malaria endemicity may be the most relevant factor to consider in the decision to stop CTX after ART-induced immune reconstitution in regions with high infectious disease prevalence. These data support the 2014 WHO CTX guidelines.Trial registrationClinicalTrials.gov NCT01425073.

Project description:IntroductionDespite declining risk of vertical HIV transmission, prophylactic cotrimoxazole (CTX) remains widely used to reduce morbidity and mortality in the event of HIV infection among exposed infants, with an inherent risk of conferring commensal antimicrobial resistance. Using data from a randomized, placebo-controlled trial of infant CTX prophylaxis, we sought to quantify emergence of antibiotic resistance.MethodsHIV-exposed uninfected infants enrolled in the Botswana Mpepu study were randomized to prophylactic CTX or placebo between 14 and 34 days of life and continued through 15 months. Stool samples were collected from a subset of participating infants at randomization, three, and six months, and stored at -70°C prior to culture. Specimens that grew Escherichia coli (E. coli) or Klebsiella species (Klebsiella spp.) underwent antibiotic susceptibility testing by Kirby Bauer method using CTX (CTX 1.25/23.75 μg) and Amoxicillin (10 μg) in Mueller Hinton agar. Fisher's exact testing was used to compare prevalence of resistance by randomization arm (CTX/placebo).Results and discussionA total of 381 stool samples from 220 infants were cultured: 118 at randomization, 151 at three months, and 112 at six-months. E. coli was isolated from 206 specimens and Klebsiella spp. from 138 specimens. Resistance to CTX was common in both E. coli and Klebsiella spp. at the randomization visit (52.2% and 37.7% respectively) and did not differ by study arm. E. Coli isolates from CTX recipients at three and six months had 94.9% and 84.2% CTX resistance, as compared with 51.4% and 57.5% CTX resistance in isolates from placebo recipients (p=0.01). Klebsiella spp. isolates from CTX recipients had 79.0% and 68.8% CTX resistance at three and six months, as compared with 19.1% and 14.3% in isolates from placebo recipients (p<0.01).ConclusionsHIV-exposed infants randomized to CTX prophylaxis had increased CTX-resistant commensal gastrointestinal bacteria compared with placebo recipients. Additional research is needed to determine the longer-term clinical, microbiologic, and public health consequences of antimicrobial resistance selected by infant CTX prophylaxis.

Project description:BackgroundIntermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).Methods and findingsA total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.ConclusionsAn effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.Trial registrationClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.

Dataset Information

Reduced bacterial skin infections in HIV-infected African children randomized to long-term cotrimoxazole prophylaxis.

Objective

Design

Setting

Participants

Intervention

Main outcome measures

Results

Conclusion

Publications

Reduced bacterial skin infections in HIV-infected African children randomized to long-term cotrimoxazole prophylaxis.

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