Skip Navigation LinksHome > April 24, 2010 - Volume 24 - Issue 7 > First-year lymphocyte T CD4+ response to antiretroviral ther...
AIDS:
doi: 10.1097/QAD.0b013e3283377a06
Epidemiology and Social

First-year lymphocyte T CD4+ response to antiretroviral therapy according to the HIV type in the IeDEA West Africa collaboration

Drylewicz, Juliaa,b; Eholie, Sergec; Maiga, Moussad; Zannou, Djimon Marcele; Sow, Papa Saliff; Ekouevi, Didier Ka,g; Peterson, Kevinh; Bissagnene, Emmanuelc; Dabis, Françoisa,b; Thiébaut, Rodolphea,b; for the International epidemiologic Databases to Evaluate AIDS (IeDEA) West Africa Collaboration

Free Access
Article Outline
Collapse Box

Author Information

aINSERM U897, France

bUniversité Victor Segalen Bordeaux 2, ISPED, Bordeaux, France

cService de Maladies Infectieuses et Tropicales (SMIT), Centre Hospitalier Universitaire (CHU) de Treichville, Abidjan, Côte d'Ivoire

dService d'Hépato-Gastro-Entérologie, Hôpital Gabriel Touré, Bamako, Mali

eCentre de Prise en Charge des personnes vivant avec le VIH (PVVIH) du Centre Hospitalier Universitaire (CHNU), Cotonou, Bénin

fSMIT, CHU de Fann, Dakar, Senegal

gProgramme PAC-CI, CHU de Treichville, Abidjan, Côte d'Ivoire

hFajara Cohort, MRC, Banjul, Gambia.

Received 26 May, 2009

Revised 21 July, 2009

Accepted 11 January, 2010

Correspondence to Rodolphe Thiébaut, INSERM U897 Epidemiology and Biostatistics, ISPED, Université Victor Segalen Bordeaux 2, 146 Rue Leo Saignat 33076 Bordeaux, France. Tel: +33 5 57 57 45 21; fax: +33 5 56 24 00 81; e-mail: rodolphe.thiebaut@isped.u-bordeaux2.fr

Collapse Box

Abstract

Objective: To compare the lymphocyte T CD4+ (CD4) response to combinations of antiretroviral therapy (ART) in HIV-1, HIV-2 and dually positive patients in West Africa.

Design and setting: Collaboration of 12 prospective cohorts of HIV-infected adults followed in Senegal (2), Gambia (1), Mali (2), Benin (1) and Côte d'Ivoire (6).

Subjects: Nine thousand, four hundred and eighty-two patients infected by HIV-1 only, 270 by HIV-2 only and 321 dually positive, who initiated an ART.

Outcome measures: CD4 change over a 12-month period.

Results: Observed CD4 cell counts at treatment initiation were similar in the three groups [overall median 155, interquartile range (IQR) 68; 249 cells/μl). In HIV-1 patients, the most common ART regimen was two nucleoside reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI; N = 7714) as well as for dually positive patients (N = 135). HIV-2 patients were most often treated with a protease inhibitor-based regimen (N = 193) but 45 of them were treated with an NNRTI-containing ART. In those treated with a NNRTI-containing regimen, the estimated mean CD4 change between 3 and 12 months was significantly lower in HIV-2 (−41 cells/μl per year) and dually positive patients (+12 cells/μl per year) compared to HIV-1 patients (+69 cells/μl per year, overall P value 0.01). The response in HIV-2 and dually positive patients treated by another regimen (triple NRTIs or protease inhibitor-containing ART) was not significantly different than the response obtained in HIV-1-only patients (all P values >0.30).

Conclusion: An optimal CD4 response to ART in West Africa requires determining HIV type prior to initiation of antiretroviral drugs. NNRTIs are the mainstay of first-line ART in West Africa but are not adapted to the treatment of HIV-2 and dually positive patients.

Back to Top | Article Outline

Introduction

As of 2007, it was estimated that the rapid scale-up of antiretroviral therapy (ART) in West and Central Africa had resulted in 430 000 patients with advanced HIV disease receiving treatment of a total in need of 1.7 million [1]. Although the prevalence seems to be declining [2–4], West Africa remains the epicentre of the HIV-2 epidemic. Compared to HIV-1, HIV-2 infection is characterized by a longer latency period [5] and a slower T lymphocyte CD4+ (CD4) depletion with a lower plasma viral load [6,7], but nonetheless leads to clinical AIDS in some instances [8,9]. Unfortunately data on the ART response in HIV-2 and dually positive patients are sparse [10–19]. There is clear evidence that non-nucleoside reverse transcriptase inhibitors (NNRTIs) are inappropriate for the treatment of HIV-2 infection [20]. However, this type of regimen remains the first-line treatment of choice in resource-limited countries [1]. Even when a protease inhibitor regimen has been used results have not always been encouraging [12,14], perhaps due to HIV-2 having a decreased susceptibility to several especially unboosted protease inhibitors [21], or to the presence of viral resistance mutations prior to the onset of an effective protease inhibitor-based therapy [13,15,22–25]. In Abidjan, a lower CD4 response at 6 months has been reported in HIV-2 and dually positive patients compared to HIV-1-infected patients [26].

In this context of a rapid scale-up of ART delivery, a consortium of leading clinicians and clinical epidemiologists from five major cities around West Africa, representing 11 adult clinic cohorts has been assembled in West Africa in the context of the global International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration of the US National Institutes of Health [27,28]. Using this international database, we describe the case management of HIV-2-infected or dually positive patients and their response to treatment compared to HIV-1-infected patients in West Africa.

Back to Top | Article Outline

Methods

Patients

The IeDEA [27] in West Africa is a prospective, observational multicohort collaboration, established since 2006, assembling data from 11 cohorts of HIV-infected adult patients in Benin [29], Gambia [5], Côte d'Ivoire [26], Mali [30] and Senegal [31,32]. For the present study, we selected all patients aged 16 or older at ART initiation with a documented date of starting ART, HIV type, and at least one measure of CD4 cell count during the first year of follow-up [33]. For the main analysis comparing NNRTI and protease inhibitor-containing regimens, patients treated by triple nucleoside combinations and other regimens were considered in a third category. The IeDEA West Africa collaboration protocol was approved by the national ethics committees of each country and each clinical site has Federal Wide Assurance (FWA) number identification.

Back to Top | Article Outline
Biological assays

In Côte d'Ivoire, the standard serologic testing algorithm for primary care centres consists in a series of two rapid HIV assays, the Determine HIV-1/HIV-2 (Abbott Diagnostics, Abbott Park, Illinois, USA), followed by the Genie II HIV-1/HIV-2 (Bio-Rad Laboratories, Marne-La-Coquette, France) [34]. The first test used for screening was the same in all countries but in Gambia where the Murex test was used (Abbott Laboratories). The second test was ImmunoComb II HIV 1 & 2 BiSpot (Orgenics Ltd, Israel) for Mali and Senegal, Hexagon HIV (Human, Wiesbaden, Germany) in Gambia. A third test based on Genie II in Mali, ImmunoComb II in Benin or Pepti-lav 1–2 assay (Bio-Rad) in Gambia could be performed in case of discrepancy between the first two test results.

Back to Top | Article Outline
Statistical analyses

The date of initiation of ART was considered as baseline. Analyses were performed on intent-to-treat basis. The change of CD4 absolute cell count after treatment initiation was analysed using piecewise linear mixed models that take into account correlation of measurements within each patient. The dynamics of CD4 response was modelled with two slopes: before and after 3 months. This change was estimated using a profile likelihood and was in agreement with previously published results [14,35]. The effect of any covariate on each average slope was assessed using a Wald test. Robustness of the results was checked after square root transformation of the CD4 [36]. Loss to follow-up was assumed in patients who were not known to have died and who were not seen for at least 1 year before closing the database for the present analysis. Potential bias due to informative drop-out was checked by comparing these estimates with those from a joint model of longitudinal measurements of CD4 and log time to drop-out [37]. As results were very robust, we are not reporting this latter analysis (available from the authors).

Back to Top | Article Outline

Results

Study population characteristics

Among 17 291 patients, including 16% lost to follow-up (LTFU), 10 073 were eligible for this analysis, including 6% LTFU (Fig. 1). Excluded patients (N = 7218) presented similar baseline characteristics (sex, age, CD4, ART regimen and previous exposure to antiretrovirals) compared to included patients. There were similar rates of patients LTFU in included and excluded patients according to HIV type (P = 0.26). In the present sample, 9482 patients were infected by HIV-1 only, 270 by HIV-2 only and 321 by both types of virus (dually positive patients). Patient characteristics according to the type of infection are reported in Table 1. Patients started combined ART between 1997 and 2007 (85% between 2004 and 2007). More than three-quarters (N = 7894, 78%) of the patients were treated by a NNRTI-based regimen. The most common combinations were stavudine (d4T) + lamivudine (3TC) + nevirapine (29%), d4T + 3TC + efavirenz (22%) and zidovudine (ZDV) + 3TC + efavirenz (19%). Among protease inhibitor-containing regimens (N = 1616), the most common combinations were ZDV + 3TC + indinavir (22%), d4T + 3TC + indinavir (15%) and ZDV + 3TC + nelfinavir (11%). Few patients (N = 470) were treated with a ritonavir-boosted regimen. The remaining other regimens (N = 563) included ZDV + 3TC + abacavir (43%) and d4T + 3TC + didanosine (8%). There were 544 (5.4%) patients who switched a major drug of their regimen (protease inhibitor, NNRTI or abacavir) during the first 12 months. The median time to switch was 4 months [interquartile range (IQR) 2; 8]. Among patients treated with an NNRTI-containing regimen, more HIV-2 and dually positive patients changed to a protease inhibitor-containing regimen compared to HIV-1 patients (P < 0.001). A total of 322 patients switched for a protease inhibitor-containing regimen: 299 were HIV-1-infected patients (4% of those treated with NNRTI), nine were HIV-2-infected patients (20% of those treated with NNRTI) and 14 were dually positive patients (10% of those treated with NNRTI). The time of changing since ART initiation was not significantly different according to the HIV-type (3, 4 and 5 months, respectively, for HIV-1, HIV-2 and dually positive patients).

Fig. 1
Fig. 1
Image Tools
Table 1
Table 1
Image Tools
Back to Top | Article Outline
CD4 response to treatment

The observed baseline median CD4 cell counts were comparable in the three groups: 155 cells/μl in HIV-1, 148 in HIV-2 and 152 in dually positive patients (P = 0.52; Table 1). The estimated baseline values according to the model were also not significantly different by type of infection (P = 0.23). The good agreement between observed and predicted CD4 cell counts over time is illustrated in Fig. 2. The slight overestimation of predicted baseline values was mostly related to missing observations at baseline.

Fig. 2
Fig. 2
Image Tools

In patients treated with a NNRTI-containing regimen, the CD4 response was weaker in HIV-2 and dually positive patients compared to HIV-1-infected patients (Table 2, Fig. 3). Although identical in the first 3 months on treatment (P = 0.62), the CD4 response was gradually blunted beyond this time point (P = 0.01) for HIV-2-infected patients [−41 cells/μl per year, confidence interval (CI) −123; 40] and dually positive patients (+12 cells/μl per year, CI −34; 58) compared to HIV-1-infected patients (+69 cells/μl per year, CI 63; 75). This led to a significantly lower CD4 cell count 12 months after ART initiation in HIV-2 (268 cells/μl, CI 175; 293) and dually positive patients (277 cells/μl, CI 252; 317) compared to HIV-1 patients (321 cells/μl, CI 319; 328) (P < .001). Of note, the CD4 response beyond the first 3 months on treatment was significantly better in dually positive patients compared to those infected by HIV-2 only (P = 0.03). These results were highly consistent when adjusted for potential confounding factors (sex, age, clinical stage and previous exposure to antiretrovirals). Thus, the estimated CD4 slopes after 3 months for female patients older than 40 years, starting ART at CDC C stage (or WHO stage 3/4) and having never been exposed to antiretrovirals were +72, −30 and +14 cells/μl per year in HIV-1, HIV-2 and dually positive patients, respectively (P = 0.03).

Table 2
Table 2
Image Tools
Fig. 3
Fig. 3
Image Tools

In patients treated by a protease inhibitor-containing regimen, the CD4 response did not differ significantly for the three HIV groups before (P = 0.73) and after 3 months (P = 0.37) (Table 2, Fig. 3). The estimated CD4 cell counts at 12 months was thus similar in HIV-2 (278 cells/μl, CI 248; 307, P = 0.22) and dually positive (271 cells/μl, CI 238; 303, P = 0.25) patients compared to HIV-1-infected patients (303 cells/μl, CI 292; 315). There were no significant differences of HIV type effect on CD4 response after 3 months between boosted and unboosted protease inhibitor-based regimens (all P values >0.35).

In patients treated by another regimen neither containing a NNRTI nor a protease inhibitor, the CD4 response was similar whatever the type of infection (P = 0.49 and P = 0.72, before and after 3 months). The results were similar even after adjustment for the potential confounding factors: age, sex, clinical stage at ART initiation and previous exposure to antiretrovirals (data not shown).

In all analyses, the CD4 responses varied substantially between individuals of the same group of treatment (variance of the individual slopes significantly different from 0, all P values <0.01). This variation was less pronounced in the group of patients treated with an NNRTI-containing regimen, irrespective of the HIV type. In all groups of treatment, the results were consistent after adjusting for centres (data not shown).

Back to Top | Article Outline

Discussion

In this international collaboration of cohorts of HIV-infected adults including the largest sample of HIV-2 and dually positive patients treated by antiretroviral drugs ever reported, we found that as expected the CD4 response was poor if the patient harboured HIV-2 and was treated with a NNRTI-containing regimen, although it was better in dually positive compared to HIV-2-only infected patients; the efficacy of protease inhibitor-containing regimens was comparable in HIV-1, HIV-2 and dually positive patients, in line for HIV-1 with other published reported [19,26,32,38,39].

There are several explanations for the use of NNRTI-based regimens in these HIV-2 and dually positive patients. First, the information on the HIV type was not always available at the time of treatment initiation. Occasionally, this information only became available after ART initiation and in the context of clinical progression. Second, in some participating clinical centres, NNRTI-containing regimens were the only treatment options available at a given time. This feature is mostly related to the challenging issue of the choice of second-line therapies in resource-limited settings [40]. Thirdly, an efavirenz regimen may have been prescribed in order to avoid protease inhibitor–rifampin interactions during TB-HIV co-treatment (although not recommended in HIV-2 infection). Finally, it is possible that some physicians did not know that NNRTIs are ineffective in HIV-2 infection. The individual justification of this therapeutic choice was not available in this dataset of routinely collected data. Overall, this underlines the need of country-specific medical education in the context of rapid scaling-up as recently advocated [32,41]. If HIV type is not available, although recommended by the WHO guidelines [42], it would be more appropriate to treat with a protease inhibitor-based regimen or a triple therapy of NRTIs if the CD4 cell count is above 200 cells/μl in HIV-2 endemic countries [42].

Although protease inhibitor-based regimens did better than those based on NNRTIs, all protease inhibitors did not present the same potency [21]. This underlines the need in studying further the efficacy of specific drugs in the special context of HIV-2 infection. In fact, observational studies like the present one cannot rule out a potential channelling bias. Furthermore, emergence of resistance mutations endorsed the need of increasing antiretroviral treatment potency in HIV-2 patients for the first-line and second-line therapy [23]. We thus believe like others [43,44] that there is a need to conduct new randomized clinical trials to optimize the care of HIV-2-infected patients.

A drawback of this study may be the absence of evaluation of virological response. Such data were not available as these tests are not routinely available. Nevertheless, the immunological response is one of the requested goals of any ART and the one currently recommended by WHO in the public health approach of antiretrovirals [42]. We do not think that the selection for enrolment (based on availability of CD4 and HIV types) or during follow-up (due to withdrawal) could impact our conclusion because there were no strong differences between included and excluded patients according to HIV type, and results were robust according to sensitivity analyses. Another issue is the lack of perfect discrimination between dually positive and HIV-2-infected patients [34]. Hence, the group of dually positive patients could have included a mixture of patients infected by HIV-2 only or both HIV-1 and HIV-2. However, the data from the present observational study come from routine practice and therefore endorse the need for confirmation algorithms of the dual infection by HIV-1 and 2 as well as the cautious use of NNRTI-containing regimens in such circumstances.

In conclusion, the scaling-up of ART in West Africa must fully incorporate the issue of HIV-2-infected patients, in terms of medical training but also for the choice of appropriate medications and diagnostic protocols at clinic and programmatic level. Finally, randomized clinical trials evaluating the new generation of antiretroviral drugs in HIV-2-infected patients are warranted to better defined public health guidelines [3,43,44].

Back to Top | Article Outline

Acknowledgements

Roles of authors: J.D., R.T., D.K.E and F.D. designed the analysis and wrote the paper. J.D. and R.T. conducted the statistical analysis, S.E. and K.P. contributed to the writing and editing of the manuscript. S.E, M.M., M.D.Z, P.S.S, K.P., E.B. contributed to the design, data and original idea.

We would like to thank Xavier Anglaret for his valuable comments on a previous version of the article.

Composition of the IeDEA-West Africa Collaboration: Primary investigator: Pr François Dabis* (INSERM U897, ISPED, Bordeaux, France).

Co-investigators: Clarisse Amani-Bosse, Franck Olivier Ba-Gomis, Emmanuel Bissagnene*, Man Charurat*, Eric Delaporte, Joseph Drabo*, Serge-Paul Eholie*, Serge-Olivier Koulé, Moussa Maiga*, Eugène Messou, Albert Minga, Kevin Peterson, Papa Salif Sow, Hamar Traoré, Marcel D Zannou*

Others members: Gérard Allou, Xavier Anglaret, Alain Azondékon, Eric Balestre, Jules Bashi, Ye-Diarra, Didier K Ekouévi*, Jean-François Eytard, Antoine Jaquet, Alain Kouakoussui, Valériane Leroy, Charlotte Lewden, Karen Malateste, Lorna Renner, Annie Sasco, Haby Signaté Sy*, Rodolphe Thiébaut, Marguerite Timité-Konan, Hapsatou Touré.

Preliminary results were presented at the 16th conference on Retroviruses and Opportunistic infections, February 8–11, 2009, abstract #600.

Funding: This study was supported by the National Institute of Allergy and Infectious Diseases (NIAID, grant 5U01AI069919-03), together with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Cancer Institute (NCI).

Back to Top | Article Outline

References

1. World Health Organization. Towards universal access: scaling up priority HIV/AIDS interventions in the health sector: progress report 2008. Geneva: WHO; 2008.

2. van der Loeff MF, Awasana AA, Sarge-Njie R, van der Sande M, Jaye A, Sabally S, et al. Sixteen years of HIV surveillance in a West African research clinic reveals divergent epidemic trends of HIV-1 and HIV-2. Int J Epidemiol 2006; 35:1322–1328.

3. Eholie S, Anglaret X. Commentary: decline of HIV-2 prevalence in West Africa: good news or bad news? Int J Epidemiol 2006; 35:1329–1330.

4. Valadas E, Franca L, Sousa S, Antunes F. 20 Years of HIV-2 infection in Portugal: trends and changes in epidemiology. Clin Infect Dis 2009; 48:1166–1167.

5. Whittle H, Morris J, Todd J, Corrah T, Sabally S, Bangali J, et al. HIV-2-infected patients survive longer than HIV-1-infected patients. AIDS 1994; 8:1617–1620.

6. Berry N, Ariyoshi K, Jaffar S, Sabally S, Corrah T, Tedder R, Whittle H. Low peripheral blood viral HIV-2 RNA in individuals with high CD4 percentage differentiates HIV-2 from HIV-1 infection. J Hum Virol 1998; 1:457–468.

7. MacNeil A, Sarr AD, Sankale JL, Meloni ST, Mboup S, Kanki P. Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J Virol 2007; 81:5325–5330.

8. Martinez Steele E, Awasana AA, Corrah T, Sabally S, van der Sande M, Jaye A, et al. Is HIV-2-induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic. AIDS 2007; 21:317–324.

9. van der Loeff MFS, Martinez Steele E, Corrah T, Awasana AA, van der Sande M, Sarge Njie R, et al. HIV-2-induced AIDS different from HIV-1-associated AIDS? AIDS 2008; 22:791–792.

10. Schutten M, van der Ende ME, Osterhaus AD. Antiretroviral therapy in patients with dual infection with human immunodeficiency virus types 1 and 2. N Engl J Med 2000; 342:1758–1760.

11. Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, Heneine W. Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antiviral Ther 2004; 9:57–65.

12. Matheron S, Damond F, Benard A, Taieb A, Campa P, Peytavin G, et al. CD4 cell recovery in treated HIV-2-infected adults is lower than expected: results from the French ANRS CO5HIV-2 cohort. AIDS 2006; 20:459–462.

13. Jallow S, Kaye S, Alabi A, Aveika A, Sarge Njie R, Sabally S, et al. Virological and immunological response to Combivir and emergence of drug resistance mutations in a cohort of HIV-2 patients in The Gambia. AIDS 2006; 20:1455–1458.

14. Drylewicz J, Matheron S, Lazaro E, Damond F, Bonnet F, Simon F, et al. Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France. AIDS 2008; 22:457–468.

15. Smith RA, Anderson DJ, Pyrak CL, Preston BD, Gottlieb GS. Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. J Infect Dis 2009; 199:1323–1326.

16. Borget MY, Diallo K, Adje-Toure C, Chorba T, Nkengasong JN. Virologic and immunologic responses to antiretroviral therapy among HIV-1 and HIV-2 dually infected patients: case reports from Abidjan, Cote d'Ivoire. J Clin Virol 2009; 45:72–75.

17. Benard A, Damond F, Campa P, Peytavin G, Descamps D, Lascoux-Combes C, et al. Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients. AIDS 2009; 23:1171–1173.

18. Sarfo FS, Bibby DF, Schwab U, Appiah LT, Clark DA, Collini P, et al. Inadvertent nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy in dual HIV-1/2 and HIV-2 seropositive West Africans: a retrospective study. J Antimicrob Chemother 2009; 64:667–669.

19. Jallow S, Alabi A, Sarge-Njie R, Peterson K, Whittle H, Corrah T, et al. Virological response to highly active antiretroviral therapy in patients infected with human immunodeficiency virus type 2 (HIV-2) and in patients dually infected with HIV-1 and HIV-2 in the Gambia and emergence of drug-resistant variants. J Clin Microbiol 2009; 47:2200–2208.

20. Ren J, Bird LE, Chamberlain PP, Stewart-Jones GB, Stuart DI, Stammers DK. Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to nonnucleoside inhibitors. Proc Natl Acad Sci U S A 2002; 99:14410–14415.

21. Brower ET, Bacha UM, Kawasaki Y, Freire E. Inhibition of HIV-2 protease by HIV-1 protease inhibitors in clinical use. Chem Biol Drug Design 2008; 71:298–305.

22. Descamps D, Damond F, Matheron S, Collin G, Campa P, Delarue S, et al. High frequency of selection of K65R and Q151 M mutations in HIV-2 infected patients receiving nucleoside reverse transcriptase inhibitors containing regimen. J Med Virol 2004; 74:197–201.

23. Gottlieb GS, Badiane NMD, Hawes SE, Fortes L, Toure M, Ndour CT, et al. Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resource-limited West Africa. Clin Infect Dis 2009; 48:476–483.

24. Landman R, Damond F, Gerbe J, Brun Vezinet F, Yeni P, Matheron S. Immunovirological and therapeutic follow-up of HIV-1/HIV-2-dually seropositive patients. AIDS 2009; 23:426–428.

25. Jallow S, Vincent T, Leligdowicz A, De Silva T, Van Tienen C, Alabi A, et al. Presence of a multidrug-resistance mutation in an HIV-2 variant infecting a treatment-naive individual in Caio, Guinea Bissau. Clin Infect Dis 2009; 48:1790–1793.

26. Toure S, Kouadio B, Seyler C, Traore M, Dakoury Dogbo N, Duvignac J, et al. Rapid scaling-up of antiretroviral therapy in 10000 adults in Cote d'Ivoire: 2-year outcomes and determinants. AIDS 2008; 22:873–882.

27. International epidemiologic databases to evaluate AIDS: West Africa. URL: http://www.iedeawestafrica.org; Last access 25 January 2010.

28. Brinkhof MW, Boulle A, Weigel R, Messou E, Mathers C, Orrell C, et al. Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality. Plos Med 2009; 6:e1000066.

29. Hounton SH, Akonde A, Zannou DM, Bashi J, Meda N, Newlands D. Costing universal access of highly active antiretroviral therapy in Benin. AIDS Care 2008; 20:582–587.

30. Boileau C, Nguyen VK, Sylla M, Machouf N, Chamberland A, Traore HA, et al. Low prevalence of detectable HIV plasma viremia in patients treated with antiretroviral therapy in Burkina Faso and Mali. J Acquir Immune Defic Syndr 2008; 48:476–484.

31. Etard JF, Ndiaye I, Thierry-Mieg M, Gueye NF, Gueye PM, Laniece I, et al. Mortality and causes of death in adults receiving highly active antiretroviral therapy in Senegal: a 7-year cohort study. AIDS 2006; 20:1181–1189.

32. Sow PS, Otieno LF, Bissagnene E, Kityo C, Bennink R, Clevenbergh P, et al. Implementation of an antiretroviral access program for HIV-1-infected individuals in resource-limited settings: clinical results from 4 African countries. J Acquir Immune Defic Syndr 2007; 44:262–267.

33. Thiébaut R, Walker S. When it is better to estimate a slope with only one point. QJM Quater J Med 2008; 101:821–824.

34. Rouet F, Ekouevi DK, Inwoley A, Chaix ML, Burgard M, Bequet L, et al. Field evaluation of a rapid human immunodeficiency virus (HIV) serial serologic testing algorithm for diagnosis and differentiation of HIV type 1 (HIV-1), HIV-2, and dual HIV-1-HIV-2 infections in West African pregnant women. J Clin Microbiol 2004; 42:4147–4153.

35. Pakker NG, Notermans DW, de Boer RJ, Roos MT, de Wolf F, Hill A, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nature Med 1998; 4:208–214.

36. Jacqmin Gadda H, Sibillot S, Proust C, Molina JM, Thiébaut R. Robustness of the linear mixed model to misspecified error distribution. Computat Stat Data Anal 2007; 51:5142–5154.

37. Thiébaut R, Jacqmin-Gadda H, Babiker A, Commenges D. Joint modelling of bivariate longitudinal data with informative dropout and left-censoring, with application to the evolution of CD4+cell count and HIV RNA viral load in response to treatment of HIV infection. Stat Med 2005; 24:65–82.

38. Stringer JS, Zulu I, Levy J, Stringer EM, Mwango A, Chi BH, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 2006; 296:782–793.

39. Nash D, Katyal M, Brinkhof MW, Keiser O, May M, Hughes R, et al. Long-term immunologic response to antiretroviral therapy in low-income countries: a collaborative analysis of prospective studies. AIDS 2008; 22:2291–2302.

40. Pujades-Rodriguez M, O'Brien D, Humblet P, Calmy A. Second-line antiretroviral therapy in resource-limited settings: the experience of Medecins Sans Frontieres. AIDS 2008; 22:1305–1312.

41. Souville M, Msellati P, Carrieri MP, Brou H, Tape G, Dakoury G, Vidal L. Physicians' knowledge and attitudes toward HIV care in the context of the UNAIDS/Ministry of Health Drug Access Initiative in Cote d'Ivoire. AIDS 2003; 17(Suppl 3):S79–S86.

42. World Health Organization. Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach:–2006 revision. Geneva: WHO; 2006.

43. Gottlieb GS, Eholie SP, Nkengasong JN, Jallow S, Rowland-Jones S, Whittle HC, Sow PS. A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa. AIDS 2008; 22:2069–2072.

44. Matheron S. HIV-2 infection: a call for controlled trials. AIDS 2008; 22:2073–2074.

Keywords:

Africa; antiretroviral therapy; CD4+ T lymphocytes; HIV-1; HIV-2; longitudinal study

© 2010 Lippincott Williams & Wilkins, Inc.

Login

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.