Spread of drug-resistant virus remains stable during expanded drug access in Côte d’Ivoire

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There have been few changes in the pattern of drug-resistant HIV circulating through Côte d’Ivoire since the introduction of large-scale programmes to access anti-HIV drugs, say researchers in Abidjan. Their findings, reported in the September issue of AIDS Research and Human Retroviruses, bolster hope that in developing regions where large-scale roll out of HIV treatment programmes is underway, rapid emergence and spread of drug-resistant resistant HIV can be avoided.

Côte d’Ivoire has the highest prevalence (4.7%) of HIV-1 infection in western Africa. Life-saving anti-HIV drugs have been available since 1998 through a programme supported by UNAIDS. Early years of the programme, the researchers report, were marked by anarchic drug distribution and non-structured treatment interruption among patients. These factors have been associated with the spread of drug-resistant HIV in the country.

Through its national blood donation programme, Côte d’Ivoire offers an HIV care service. Researchers associated with the French ANRS (Agence Nationale de Recherches sur le SIDA) have drawn on the service to create the Primo-CI ANRS 1220 cohort, an on-going longitudinal study of a group of newly infected HIV-positive individuals.

Glossary

gene

A unit of heredity, that determines a specific feature of the shape of a living organism. This genetic element is a sequence of DNA (or RNA, for viruses), located in a very specific place (locus) of a chromosome.

gp41

A glycoprotein on the HIV envelope. HIV enters a host cell by using gp41 to fuse the HIV envelope with the host cell membrane.

longitudinal study

A study in which information is collected on people over several weeks, months or years. People may be followed forward in time (a prospective study), or information may be collected on past events (a retrospective study).

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

For the current study, Toni and colleagues recruited 105 cohort participants between July 2002 and June 2006. Eligible patients had a recent HIV-1 infection (an estimated date of seroconversion within the last 36 months) and had never received anti-HIV treatment.

The study population comprised 47% women and had a mean age of 30 years. The median time since estimated date of seroconversion was nine months. Median CD4 cell count was 445 cells/mm3 and viral load, 25,000 copies/ml. Of the 105 samples collected, 100 contained testable material.

Blood samples were assayed for mutations in the viral gene sequences of reverse transcriptase (RT), protease and gp41. RT is the target of the nucleoside analogue classes of anti-HIV drugs (NRTIs and NNRTIs), while protease is the target of the protease inhibitor class of anti-HIV drugs (PIs). Viral gp41 function is blocked by the fusion inhibitor T-20 (enfuvirtide, Fuzeon).

Genotype testing revealed resistance mutations in the samples from six patients, leading to a prevalence of 6%. One patient had a mutation in the protease gene, while the remaining five carried mutations in the reverse transcriptase gene. There were no resistance mutations noted in the gp41 gene among the 47 samples tested for this gene.

The identified protease mutation, M46L, encodes resistance to indinavir (Crixivan). The RT mutations included M41L and K219Q, which are selected by thymidine analogues AZT (zidovudine, Retrovir) and d4T (stavudine, Zerit), and Y115F, which is associated with abacavir (Ziagen) resistance. The final two mutations, K101E and K103N + P236L, are associated with resistance to NNRTIs.

According to resistance algorithms developed by the ANRS, three patients (prevalence of 3%) carried a viral strain resistant to at least one drug, with one patient resistant to indinavir and two resistant to NNRTIs efavirenz (Sustiva) and nevirapine (Viramune).

The researchers note that this resistance pattern is consistent with the spectrum of drugs available in the country. Indinavir was the first protease inhibitor to be offered in Côte d’Ivoire, while nevirapine was used in early programmes to prevent mother-to-child transmission.

These results are similar to earlier results from the Primo-CI ANRS 1220 cohort. In 2001–2002, the researchers performed a similar study on a group of 107 untreated patients and found a prevalence of resistance mutations of 5.6%. Other groups have recently published similar studies of groups in Switzerland and the UK.

The researchers conclude that “the stability of the prevalence of the drug resistance mutations between 2001 and 2002 and 2002 and 2006 also suggests that the more recent large-scale programs of access to HAART that have been launched in the country since 2002 might have had fewer consequences in terms of drug resistance spread.”

References

Toni TD et al. HIV-1 Antiretroviral drug resistance in recently infected patients in Abidjan, Côte d’Ivoire: A 4-Year Survey, 2002–2006. AIDS Res Hum Retroviruses 23(9): 1155 – 1160, 2007.