The areas that has highest problems of HIV infection, also experiences the biggest burden of malaria. Sub-Saharan Africa remains the region most heavily affected by HIV.  Each year 350–500 million cases of malaria occur worldwide, and over one million people die, most of them young children, in sub-Saharan Africa. Methods used to prevent the spread of malaria disease endemic areas include prophylactic drugs, mosquito eradication, and the prevention of mosquito bites. Attention to non-traditional malaria therapies that may have antimalarial effects is ongoing given the magnitude of malaria related morbidity and mortality.  Identifying drugs, such as those used in the treatment of HIV/AIDS (which are becoming more available in sub-Saharan Africa), with antimalarial activity will provide additional tools in comprehensive malaria control and prevention programs

Areas of high HIV prevalence and intense malaria transmission significantly overlap especially sub-Saharan Africa where a majority of HIV-infected individuals also live in malaria-endemic regions.  Sub-Saharan Africa remains the region most heavily affected by HIV, accounting for 67% of all people living with HIV and 75% of AIDS deaths in 2007.  Each year 350–500 million cases of malaria occur worldwide, and over one million people die, most of them young children, in sub-Saharan Africa.                                           

Recent studies have indicated that the interaction between HIV and malaria infection is bi-directional and synergistic. HIV-infected persons are at increased risk for clinical malaria and potential malaria treatment failure. In addition to an apparent increased vulnerability to malaria parasitemia in HIV-infected adults living in malaria endemic regions, malaria may also enhance HIV replication.  Evidence suggests that HIV/malaria coinfection is associated with increased HIV viral load and may therefore impact negatively upon HIV disease progression and/or increase the risk of HIV transmission.  In Kenya, the burden of both HIV and malaria remains significant.  However, while clinic programs and research studies are ongoing targeting HIV and malaria separately, very little if any research is ongoing focusing upon the HIV/malaria co-infection.

Methods used to prevent the spread of malaria disease endemic areas include prophylactic drugs, mosquito eradication, and the prevention of mosquito bites. Attention to non-traditional malaria therapies that may have antimalarial effects is ongoing given the magnitude of malaria related morbidity and mortality.  Identifying drugs, such as PIs used in the treatment of HIV/AIDS (which are becoming more available in sub-Saharan Africa), with antimalarial activity will provide additional tools in comprehensive malaria control and prevention programs.

This study will test the superiority of LPV/r-based ART compared with nNRTI-based ART clearance of Pf SCP.  The primary endpoint is PCR defined clearance of Pf parasitemia on three consecutive occasions within a 24-hour period. HIV-infected participants ≥18 years with CD4+ counts >200 and <350 cells/mm³ who will be starting ART and have Pf SCP will be enrolled and randomized to receive either LPV/r or nNRTI-based ART for 15 days. After the 15 day Pf SCP clearance evaluation, all participants will receive nNRTI-based ART plus TMP/SMX prophylaxis to take for 15 days.

The Kericho site will recruit about 20-30 participants, in part dependent upon timing of protocol activation compared to the other 5 sites in this international, multi-center study.  Recruitment will be focused at the Kericho District Hospital HIV clinic.  Nearby health and HIV Testing and Counseling (HTC) facilities under the KEMRI/WRP PEPFAR program will also be utilized.  Participants will be followed for 30 days. The site accrual rate is estimated to be 2-3 participants per month; hence estimated duration of accrual is about 12 months.

If PIs are shown to have marked benefit in clearance of subclinical malaria, such information would be informative to both clinical researchers (i.e. KEMRI) in considering future HIV/malaria infection research as well as policy stakeholders (i.e. Ministry of Health) in considering optimal treatment and prevention initiatives.