Rapid progression of CD4 cell decline and subsequent response to salvage therapy in HIV-2 infection

In 1991, a 32-year-old male student from West Africa presenting with non-specific musculoskeletal symptoms was found to be HIV seropositive. His only HIV risk factor was heterosexual contact in his home country. Past history was negative except for multiple episodes of malaria. Positive physical findings were limited to genital warts and bilateral 1–2 cm axillary nodes. Laboratory investigations revealed HIV-2 antibodies by enzyme immunoassay, confirmed by Western blot and radioimmunoprecipitation assay. Co-existing HIV-1 infection was excluded by Western blot and subsequently by polymerase chain reaction (Roche Diagnostic Systems Inc., Branchburg, NJ, USA). The initial CD4 cell count was 820 cells/mm3 (CD4% 35). Subsequent trends in CD4 cell count and CD4 cell percentage are illustrated in Fig. 1 along with his antiretroviral therapy.Fig. 1.: Absolute CD4 cell count and CD4 cell percentage. ––▒–– Absolute CD4 cell count; ––♦–– CD4% of total lymphocytes. ddC, Zalcitabine; ddI, didanosine; d4T, stavudine; HU, hydroxyurea; IDV, indinavir; 3TC, lamivudine; VL, HIV-2 viral load; ZDV, zidovudine. *Investigational protocol.He received a year of isoniazid prophylaxis for a positive tuberculin skin test, cotrimoxazole was prescribed from May 1994 to the present, and azithromycin was started in June 2000. The patient's course was complicated by falciparum malaria and Salmonella diarrhoea after a visit home to Africa in October 1995, pauci-articular arthritis, granulomatous uveitis, a persistent nodular rash with inconclusive histological characteristics and an episode of herpes zoster. We were initially unable to obtain HIV-2 viral load measurements. In late 1999, the Centers for Disease Control and Prevention in Atlanta, using a prototype research assay detailed elsewhere [1] reported the HIV-2 viral load at 92 360 and 68 776 (mean 80 568) HIV-RNA copies/ml. All subsequent viral load measurements were performed using the same assay. In March 2000, when the patient's CD4 cell count was 40 cells/mm3 (2%), he was enrolled in an ABT-378/r (lopinavir/ritonavir) early access protocol, combining the study drug with abacavir, didanosine, and hydroxyurea. In June 2000, the HIV-2 viral load was less than 100 viral RNA copies/ml and a CD4 cell count in October 2000 was 60 cells/mm3 (4%). When last assessed in December 2000, he was feeling ‘better than he had in years', his CD4 cell count was 100 cells/mm3 (7%), and a repeat HIV-2 viral load in December 2000 remained less than 100 HIV RNA copies/ml. He has since left our area and been lost to follow-up. Our patient's experience illustrates several points. First, HIV-2 is relatively rare in north American practice. Up to 1996, only 67 cases had been identified in the USA [2]. Second, although HIV-2 is generally associated with less rapid disease progression than HIV-1 [3,4], our patient demonstrated a relatively rapid CD4 cell count decline from over 800 cells/mm3 to less than 50 cells/mm3 over a 5-year period. Third, now that quantitative viral load measurement has become an essential element in the management of HIV infection in industrialized nations, the care of patients with HIV-2 is hampered by difficulty in accessing HIV-2 viral load measurements. No HIV-2 viral load test has been approved in Canada to date. Fourth, there is very little information to guide therapy for HIV-2 infection [5–9], except for the knowledge that non-nucleoside reverse transcriptase inhibitors are ineffective [10]. Published experience with highly active antiretroviral therapy is limited to case reports and two case series of six [9] and three [6] patients, neither of which provides great detail regarding treatment outcome. No trial of antiretroviral therapy has been published on HIV-2 to date, and there are no previous reports of ‘salvage therapy’ in HIV-2 infection. The manufacturer of lopinavir does ‘not have any specific efficacy or safety information for patients infected with HIV-2’ (Rafik Zakhari, Abbott Laboratories, personal communication). Although we were unable to document the viral load response to earlier treatment regimens, they had clearly not led to any improvement in his CD4 cell count, and his viral load was high when first measured on combination therapy. Therefore, there is little doubt that he had failed previous therapies. In retrospect, it is likely that the treatment changes early in his course were suboptimal, because of the lack of knowledge regarding ‘salvage therapy’ at that time. We cannot be certain whether the gratifying clinical and viral load response to salvage therapy was simply caused by the introduction of four new drugs or whether one or more of the components of his second regimen had anti-HIV-2 activity superior to that of the agents used initially. Finally, our patient is planning to return to Africa, where it is unlikely that he will be able to access antiretroviral drugs to continue his therapy. In conclusion, there is a need to make HIV-2 viral load measurement available. Antiretroviral drugs in current use and those under development should be tested against strains of HIV-2, and efforts made to coordinate clinical trials in patients infected with this virus. Stan C. Houston Lil J. Miedzinski Laura D. Mashinter

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