HIV–2 is a genetically distinct virus from HIV-1, the latter of which is by far the most common form of HIV worldwide. HIV-2 is found almost exclusively in West Africa, and has tended to spread only to countries with strong links to this region of Africa: in Europe these are France and Portugal.
HIV-2 is much harder to transmit, appears to be less pathogenic and is much more difficult to isolate from the blood than HIV-1. It has been found that individuals infected with HIV-2 are asymptomatic for much longer than those infected with HIV-1, and may not develop high levels of virus in their blood for fifteen to twenty years after infection, by which time they may be much less sexually active or past childbearing age. Treatment of HIV-2 is similar to HIV-1, with the exception that NNRTIs are not recommended due to HIV-2’s natural resistance to this class of drugs.
The French HIV-2 cohort began in 1994, and is an ongoing prospective study in 75 clinical centres. In order to determine the best time to start antiretroviral therapy, researchers studied the association between HIV-2 viral load and clinical progression or death in 217 HIV-2 infected adults (60% of whom were women) between May 1994 and December 2001.
Overall, 183 patients (84%) had links to an African endemic region of HIV-2 infection. The majority (73%) of the cohort were born in West Africa, although a significant minority (22%) were born in Europe, 85% of them in France. The majority of transmissions (84%) were heterosexually-acquired, with another 9% acquired through blood transfusions, 2% homo/bisexually and 6% unknown.
At enrolment into the study, the median CD4 count was 436 cells/mm3 and 31 (14%) already had AIDS-defining events. Since HIV-2 viral load tends to be lower than HIV-1 levels in this cohort HIV-2 viraemia was isolated from just 24.5% of peripheral blood mononuclear cell (PBMC) samples at baseline, and just 1.8% of plasma samples. However, HIV-2 RNA was measurable in just under half (48%) of those who had samples available (n=135). The median viral load was 3 log10 copies/ml.
The researchers note that cellular viraemia, plasma RNA and proviral DNA were more frequently detected in those cohort members with CD4 counts below 200 cells/mm3; and those with both negative plasma RNA and negative proviral DNA all had CD4 counts above 300 cells/mm3.
Just over half of the cohort who were followed-up and included in the outcome analysis (n=179) were treated with at least one antiretroviral for a median of 19 months: 16% received one NRTI, 27% two NRTIs, 9% three NRTIs and 48% HAART. Single and dual therapy reflects that the study began in the pre-HAART era.
Thirteen cohort members died during follow-up; six deaths were due to AIDS-related illnesses, four were due to bacterial infections, two due to cirrhosis and one from hypertensive cardiopathy. The overall survival rate was 97% one year after enrolment (95% confidence interval [CI], 94.4-99.6) and 93.4% after three years (95% CI, 89.1-97.7).
The probability of remaining AIDS-free one and three years after enrolment was 96.6% (95% CI, 93.6-99.5) and 94.5% (95% CI, 90-98.5), respectively. Of the AIDS-defining events that took place during follow-up, six were TB, two were wasting syndrome and one was neurotoxoplasmosis. Four of the TB cases occurred at CD4 counts above 200 cells/mm3.
The two factors significantly associated with clinical progression were age over 40 years (hazard ratio [HR], 11.3, p = 0.03) and plasma HIV-2 RNA level (HR, 2.5 per 1 log10copies/ml increase). The two factors significantly associated with death were positive plasma RNA (HR, 3.11; 95% CI, 1.4-6.9; p = 0.005) and AIDS status (HR, 9.1, 95% CI, 1.6-52.1; p=0.02).
The risk of progression was 26% amongst those cohort members with plasma RNA levels greater than 1000 copies/ml at baseline, versus 6% in those with less than 1000 copies/ml (p
The authors conclude that this cohort study confirms that HIV-2 progresses much more slowly than HIV-1, and that measuring plasma viral load “is useful for measuring the risk of clinical progression. It should therefore be used for the management of HIV-2 infected patients, for deciding if antiretroviral therapy is needed. An undetectable plasma HIV-2 RNA (using a cut-off limit of 250 copies/ml) is associated with a very low risk of progression in asymptomatic patients and suggests that treatment may not be required.”
However, they add that the precise level of HIV-2 RNA at which to begin antiretroviral therapy has not yet been defined, and that treatment must be balanced against the risks of long-term side-effects like lipodystrophy.
Further information on this website
HIV-2 does not protect against HIV-1 infection - news story
HIV-2 globally - About the Epidemic
Matheron S et al. Factors associated with clinical progression in HIV-2 infected-patients: The French ANRS cohort AIDS 17: 2593-2601, 2003.