Mefloquine Prophylaxis in HIV-1 Individuals: a Randomized Placebo-controlled Trial

Mefloquine Malaria Prophylaxis in HIV-1 Infected Individuals and Its Influence on the Evolution Towards AIDS: a Randomized Placebo-controlled Trial

This is a randomized placebo controlled trial. Malaria chemoprophylaxis with mefloquine in asymptomatic HIV-infected adults living in a malaria endemic region of Luanshya, Zambia will be compared to a placebo control group and followed up for 18 months.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: placebo; Drug: mefloquine

Detailed Description

In Zambia prompt treatment of malaria cases is the mainstay of malaria control; antimalarial chemoprophylaxis is not currently recommended for general use so that the use of placebo as a comparator in this study is justified. We will analyse safety and efficacy of mefloquine, malaria and AIDS related parameters at predefined time points, and verify if this intervention could produce a slower decrease in CD4 counts compared to passive case management of malaria.

This is a randomized placebo controlled trial. Malaria chemoprophylaxis with mefloquine in asymptomatic HIV-infected adults living in a malaria endemic region of Luanshya, Zambia will be compared to a placebo control group and followed up for 18 months.

Specific designed studies taking into account possible confounding parameters (and interactions) are needed to measure the impact of malaria control in an HIV endemic environment. In particular, the question should be answered if malaria control has an impact on the disease progression of HIV. The possible impact of these interventions on morbidity and mortality taking into account these parameters might have a major public health impact. This might be on the use of antiretroviral drugs, the incidence of clinical (eventually severe) malaria and spread of antimalarial resistance through immune compromised HIV patients (with and without antimalarial treatment).

Studies of alternative strategies that contribute (next to antiretrovirals) to the control and prevention of HIV pandemic are equally important and urgently needed. The need to design these strategies is critical given the high incidence of malaria and HIV in countries in Sub Saharan Africa such as Zambia and its serious impact on survival and the socio-economic situation. Moreover, a cost-benefit analysis might show that some alternative strategies have a major impact on the field with less technical, financial and social constraints than the strategies recommended so far.

All HIVP patients will be treated for opportunistic infections (OI) and receive antiretroviral drugs following the National guidelines on Management and Care of Patients with HIV/AIDS (also if this occurs after the study period). At the time they need cotrimoxazole prevention or/and receive antiretrovirals they would have reached a study endpoint and will be excluded from the trial though the follow up will continue.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Zambia
  • Cupperbelt
    • Ndola, Cupperbelt, Zambia
      • Tropical Disease Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Permanent residents of the Luanshya district
• Males and non pregnant adults between 18 and 50 years old.
• Having a CD4 cell count of least 350 perµL at enrolment
• HIV sero-status determined at the VCT of the health center.
• No obvious underlying disease at time of enrolment
• Signed informed consent

Exclusion Criteria:

• HIV stage III or IV following the WHO classification (see attached documents regarding policy in Zambia)
• Evidence of underlying chronic diseases (cardiac, renal, hepatic, malnutrition, TB).
• Intent to move out of the study catchment area during the study period
• History of allergy to MQ (or related drugs) or sulfa drugs
• Chorionic gonadotrophic hormone in urine or obvious pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo, tablet	Drug: placebo; tablet, once weekly
Experimental: mefloquine, tablet	Drug: mefloquine; tablet, once weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of decline of CD4 counts between different time points	months 0, 6, 12 and 18
Proportion of patients entering the AIDS stage (WHO stage 3,4)	during 18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean difference in log plasma viral load at different time points,	during 18 months
Rate of decline of humoral immunity between different time points.	during 18 months
Proportion of patients with parasitaemia at the end of the intervention.	during 18 months
All cause disease incidence and prevalence (including malaria, TB)	during 18 months
Proportion of patients with Adverse event during monitoring	during 18 months
Prevalence of anaemia at different time points	during 18 months
Incidence of severe anaemia	during 18 months

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium
• Investigators: Study Director: Umberto D'Alessandro, MD,MSc, PHD, Institute of Tropical Medicine Antwerp

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 5, 2006
• First Submitted That Met QC Criteria: September 6, 2006
• First Posted (Estimate): September 7, 2006

Study Record Updates

• Last Update Posted (Estimate): May 24, 2011
• Last Update Submitted That Met QC Criteria: May 23, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: HIV-1 malaria Clinical Trial
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Mefloquine
• Other Study ID Numbers: Mefloquine HIV zambia