Investigation of an Extensive Outbreak of HIV Infection Among Children in Sindh, Pakistan: A Case-Control Study

Background: In April 2019, an HIV outbreak predominantly affecting children occurred in Larkana District, Sindh, Pakistan. By December 2019, 881 of 21962 children screened had tested positive for HIV. We conducted an individually-matched case-control study to investigate risk factors for HIV infection. Methods: Cases (children aged <16 years registered for pediatric HIV care in Larkana city) and controls (HIV-uninfected children matched 1:1 by age, sex and neighbourhood) were sampled concurrently. An interviewer-administered questionnaire was used to collect data on possible risk factors for HIV acquisition and a blood sample was collected from all participants for hepatitis B and C serology. Mothers of all participants were tested for HIV. Adjusted odds ratios (OR) were estimated using conditional logistic regression to assess factors associated with HIV infection. Findings: Between July and December 2019, 401 HIV cases and 401 controls were recruited. The prevalence of hepatitis B surface antigen and hepatitis C antibodies was 18∙2% (95% CI 14∙5-22∙3) and 6∙5% (95% CI 4∙3-9∙4) respectively among cases, and 5∙2% (95% CI 3∙3-7∙9) and 1∙0% (95% CI 0∙3-2∙5) respectively among controls. Overall, 7.1% mothers of cases and no mothers of controls were HIV positive. In the 6 months prior to recruitment, 226 (56∙4%) cases and 32 (8∙0%) controls reported >10 injections, and 291 (72∙6%) cases and 78 (19∙5%) controls had received an intravenous infusion. At least one blood transfusion was reported in 56 (14∙0%) cases and 3 (0∙8%) controls in the past two years. HIV infection was independently associated with history of more injections and infusions (adjusted OR (aOR) 1∙50; 95% CI 1∙18-1∙92), blood transfusion (aOR 114∙8; 95% CI 6∙35-2074), and increased frequency of private clinic and government hospital visits (p<0∙001). Interpretation: The predominant mode of transmission in this outbreak was parenteral, likely due to unsafe injection practices and poor blood safety. Funding Statement: Department of Pediatrics and Child Health, the Aga Khan University, Karachi. Declaration of Interests: RAF reports funding from the Wellcome Trust during the conduct of the study. All other authors declare no competing interests. Ethics Approval Statement: All caregivers provided written informed consent. All children aged >10 years provided written assent with caregivers signing the assent form. The study was approved by the Ethics Review Committee of the Aga Khan University (2019-1536-4200).