Since its discovery in 1985, there have been approximately 1–2 million cases of HIV-2 infection worldwide. HIV-2 is endemic to West Africa, but is also seen in historically associated nations, including France, Portugal, Angola, Brazil, India, and Mozambique [1–3]. In the United States, HIV-2 is rarely reported. The Centers for Disease Control (CDC) documented only 166 cases between 1988 and 2010 [3,4]. Due to limited clinical experience and laboratory testing, HIV-2 management in the United States poses a significant challenge.
A 54-year-old male with hypertension was admitted with exertional dyspnea, night sweats, and nonproductive cough. He denied weight loss, fever, or other complaints. He emigrated from the Gambia to the United States in 1997. He had unprotected sex with two female partners in Africa in 2005 and 2011 and no subsequent sexual encounters, blood transfusions or intravenous drug use.
On physical exam, the patient was afebrile with a blood pressure of 149/72 mmHg, a heart rate of 113 bpm, and normal respiration and oxygen saturation. Cardiac troponins were negative. The remaining physical exam and laboratory results were unremarkable. Imaging revealed sinus tachycardia on echocardiogram, bilateral upper lobe opacities on chest X-ray and ground glass opacities in all lobes on thoracic CT scan.
The patient later developed a fever of 38.6 °C. Blood and respiratory cultures were negative, but respiratory smear was positive for Pneumocystis jirovecii, prompting HIV evaluation. The CD4+ count was 29 cells/μl (2%), but HIV-1 RNA was not detected. The HIV-1/2 antigen/antibody immunoassay was reactive and the HIV-1/2 antibody differentiation assay indicated HIV-2 with HIV-1 cross-reactivity. Testing sent to the New York State Department of Health and CDC confirmed HIV-2 monoinfection with HIV-2 RNA of ∼200 copies/ml.
The patient received steroids and intravenous trimethoprim-sulfamethoxazole for pneumocystis pneumonia (PCP). He developed acute kidney injury and was switched to pentamidine and later atovaquone (G6PD was unknown). Interferon-gamma release assay, urine histoplasma antigen, and respiratory culture for acid-fast bacilli were negative. Serum cryptococcal antigen was positive (titer 1 : 128), but cerebrospinal fluid cryptococcal antigen was negative, and so fluconazole was started for presumed pulmonary cryptococcosis. He completed 21 days of PCP treatment and was started on abacavir−lamivudine−dolutegravir (HLA-B*5701 negative) for HIV-2 treatment and prophylaxis for PCP and Mycobacterium avium-intracellulare (MAI) infection. He was clinically improved at discharge and 2-week follow-up.
HIV-2 is less virulent than HIV-1. Studies show that 25–33% of treatment-naïve HIV-2 patients present with undetectable viral loads and 85% remain asymptomatic at least 8 years after infection [2,5–7]. But at low CD4+ counts, clinical progression mirrors HIV-1 infection [2,5]. Two Gambian studies of HIV-1, HIV-2, and dually infected patients with AIDS found similar rates of clinical progression, immune reconstitution inflammatory syndrome, and mortality [8,9].
Given its rarity, HIV-2 may be underdiagnosed in the United States. Although the fourth generation antigen/antibody immunoassay detects both viruses, the CDC recommends testing for HIV-2 if HIV tests are inconclusive or negative despite positive clinical evidence, particularly for West Africans. Suspected HIV-2 cases should be reported to state health departments for confirmatory testing [6,10,11].
Pending ongoing clinical trial research, in-vitro data and small studies guide HIV-2 antiretroviral therapy (ART) recommendations. Nucleoside reverse transcriptase inhibitors (NRTIs) are effective but with a lower threshold for resistance to HIV-2 than HIV-1 . Darunavir, lopinavir, and saquinavir are the most active protease inhibitors; other protease inhibitors are not recommended . Integrase strand transfer inhibitors (INSTIs) have potent HIV-2 activity. Dolutegravir's high-barrier to resistance may be advantageous as dolutegravir given twice daily was effective in HIV-2 patients failing raltegravir . Maraviroc is not favored as HIV-2 uses many different chemokine receptors and nonnucleoside reverse transcriptase inhibitors and enfuvirtide are intrinsically resistant [15,16]. Recommended treatment for HIV-2 consists of two NRTIs with one HIV-2 active boosted protease inhibitor or INSTI (Fig. 1) .
Evaluating the virologic response to ART in HIV-2 patients is difficult in the United States. Although CD4+ should be routinely checked, only two laboratories offer HIV-2 RNA testing and none offer HIV-2 resistance testing. Thus, signs and symptoms of virologic failure, clinical progression, and opportunistic infections must be closely monitored .
Opportunistic infections in HIV-2 such as cryptococcosis, cytomegaloviral infections, MAI infection, PCP, toxoplasmosis, and tuberculosis have been described, but details regarding effective treatment options are sparse [2,17]. Currently, treatment and prophylaxis recommendations are extrapolated from HIV-1 data, but studies in HIV-2 patients are critically needed.
The current case demonstrates the classic presentation of HIV-2 infection with a prolonged asymptomatic period but eventual progression to AIDS. We also explore the challenges of treating HIV-2 and associated opportunistic infections in the United States because of limited laboratory information and clinical data.
Nidhi Saraiya wrote the introduction and discussion sections, edited all sections, and prepared the manuscript for submission. Vamsi Kanagala wrote the case section. Marilou Corpuz advised both writers on writing and content, and edited all sections.
Conflicts of interest
There are no conflicts of interest.
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