With increased access to HIV treatment throughout Africa, a generation of HIV positive children is now transitioning to adulthood while living with a chronic condition requiring lifelong medication, which can amplify the anxieties of adolescence. This qualitative study explored how adolescents in Tanzania with HIV experience their nascent sexuality, as part of an evaluation of a home-based care programme. We interviewed 14 adolescents aged 15–19 who had acquired HIV perinatally, 10 of their parents or other primary caregivers, and 12 volunteer home-based care providers who provided support, practical advice, and referrals to clinical services. Adolescents expressed unease about their sexuality, fearing that sex and relationships were inappropriate and hazardous, given their HIV status. They worried about having to disclose their status to partners, the risks of infecting others and for their own health. Thus, many anticipated postponing or avoiding sex indefinitely. Caregivers and home-based care providers reinforced negative views of sexual activity, partly due to prevailing misconceptions about the harmful effects of sex with HIV. The adolescents had restricted access to accurate information, appropriate guidance, or comprehensive reproductive health services and were likely to experience significant unmet need as they initiated sexual relationships. Care programmes could help to reduce this gap by facilitating open communication about sexuality between adolescents and their caregivers, providers, and HIV-positive peers.