Table 2.
Summary of the included studies related to HIV-1 and HTLV-1/2 coinfection.
| Study | Study Design, country | Population Characteristics | Coinfection | Main outcomes: Coinfected vs. Monoinfected | Other outcomes |
|---|---|---|---|---|---|
| Page (15) | Cohort, USA | Total n = 107 Male: 78 (72.9%) Age >35: n = 58 | HTLV-1/2 and HIV-1, n = 23 | Coinfected patients had shorter survival, [HR: 3.326; CI 95% (1.12–9.87)] and were more likely to die of AIDS [RR: 2.92, CI 95% (1.30–6.95)]. | Death was mainly due to respiratory impairment involving either Pneumocystis carinii pneumonia or other opportunistic infections in the lungs. |
| Kaplan (16) | Cross- sectional, USA | Total n = 184 Male: 127 (85.1%) Age <40 n = 144 | HTLV-2 and HIV-1, n = 36 | Ichthyosis: 8/36 (22.2%) vs. 12/148 (6.8%), p = 0.038. | Clinical presentation of coinfected patients was far from usual acquired ichthyosis: the scales were large, rhomboidal, and extremely coarse, resembling those of lamellar ichthyosis and frequent palmoplantar keratoderma. |
| Visconti (11) | Cohort, Italy | Total n = 145 Male: 103 (71%) Age: m = 28.8 (19–41) | HTLV-2 and HIV-1, n = 22 | Survival was longer for coinfected patients (p = 0.08). No difference related to AIDS progression (p = 0.10) or death (p = 0.30) was found. |
When the analysis was restricted to (IV A) or (IV) stage, no survival-related difference was found, p = 0.5. |
| Schechter (7) | Retrospective nested, case control, Brazil | Total n = 126 Male: 90 (71.4%) Age: m = 38.2 (±9.2) | HTLV-1 and HIV-1, n = 27 | AIDS progression:4(15%) vs. 3(3%), [OR: 4.9; 95% CI (1.1–21.9)]. WHO late clinical stages (3 and 4): 12(44%) vs. 21 (21%), [OR: 3.1; 95% CI (1.2–7.8)]. |
CD4+ T cell count: 21 (88%) of coinfected patients had a greater count than 0.200 X109 cells/ L vs. 52 (56%) of monoinfected ones [OR: 4.0; 95% CI (1.3–12.5)]. Only 5% of monoinfected and none of coinfected (0%) were on ART, p = 0.58. |
| Giacomo (17) | Cross- sectional, Italy | Total n = 49 Male: 33 (67%) Age: m = 32.4 (±4.1) | HTLV-2 and HIV-1, n = 5 | Progression to AIDS and death from AIDS was slower in coinfected subjects, p = <0.01, no difference was found in the cumulative survival estimated by Cox test. p = 0.23. | Higher CD4cell count at 36–47 months for coinfected 625 ± 231 vs. 390 ± 231 for monoinfected ones, p = 0.23. |
| Hershow (18) | Cohort, USA | Total n = 370 Female:101(27.3%) Age: m = 31.4 (± 8.6) | HTLV-2 and HIV-1, n = 61 | Coinfection was not associated with AIDS or AIDS progression, Univariate RH: 0.82, 95% CI (0.34–1.94); Multivariate RH: 0.74, 95% CI (0.28–1.97). | Coinfected patients had a higher CD4 cells median at the time of death: 113 vs. 10 cells, p= 0,023. |
| Brites (8) | Case-Control, Brazil | Total n = 198 Male: 75% Age: 32.6 (m = 33) | HTLV-1 and HIV-1, n = 63 | Coinfected patients had a shorter survival than monoinfected ones: 1,849 vs. 2,430 days, p = 0.001. | Patients who died of AIDS had an initial CD4 cell count similar to survivors: 371 ± 244 vs. 481 ± 417 cells/mm3, p = 0.7 |
| Brites (19) | Cross-sectional, Brazil | Total n = 91 Female: 52(57.1%) Age: m = 36.25 (±16.45) | HTLV-1 and HIV-1, n = 18 | Higher mortality rate among coinfected patients: n = 5, p = 0.01. | Severe forms of scabies are strongly associated with HTLV-1 infection OR: 3.0; 95% CI (1.85–4.86). Crusted form was highly predictive of coinfection (p = 0.01). All deaths were on coinfected, presented with crusted scabies and with a deeper degree of immunodeficiency. |
| Zehender (20) | Cohort, Italy | Total n = 90 Male: 64 (71%) Age:m = 32.5 (23-55) | HTLV-2 and HIV-1, n = 30 | Higher probability of developing PN in coinfected than in monoinfected patients, p = 0.004. | None of the patients with PN were on ART when the symptoms appeared. ART use in coinfected individuals was less frequent 16 (53.3%) compared with monoinfected 49 (81.6%). AIDS progression rate was not different between groups, p = 0.1 |
| Castro-Sansores (21) | Prospective cross- sectional, Mexico | Total n = 192 Male: 149(78%) Age: m = 32.7 (17–75) | HTLV-2 and HIV-1, n = 24 | AIDS-defining pathologies were more frequently observed in the coinfected patients: 9/19(47%) vs. 30/128(23%) p = 0.02. | Similar Initial lymphocytes CD4 (cell/mL): 261 ± 232 vs. 202 ± 146, p = 0.4. Candidiasis more frequently in coinfected: 21/168 (12%) vs 10/24 (42 %), p = 0.0004 |
| Collins (22) | Case control, Peru | Total n = 150 Male: 121 (87%) Age: m = 41 (± 11) | HTLV-1 and HIV-1, n = 50 | Survival: 47 months (range = 17–77) vs. 85 months (range = 70–100) p = 0.06. Death rate: 7 (32%) vs. 7 (13%), [HR 1.6 (95% CI 1.0–2.8; p = 0.06)]. ART Use: 22/50 (44%) vs. 53/100 (53%), p = 0.5. |
The variables associated to death were: Age > 40 years: HR Unadjusted = 1.8 (95% CI 1.1–3.0).-CD4+ <100 cell/μL, HR Unadjusted = 3.8 (95% CI 1.4–10.2).–AIDS, HR Adjusted = 13.5 (95% CI 1.4–132.3).-No HAART use, HR Adjusted = 96.5 (95% CI 17.0–546.3). AIDS clinical stage [HR: 13.5, 95% CI (1.4 −132.3)] and lack of antiretroviral therapy [HR: 96.5, 95% CI (17.0–546.3)], were associated to a higher risk of dying. |
| Pedroso (23) | Nested case control, Brazil | Total n = 74 Female: 39 (52.7%) Age: 2 to 16 years | HTLV-1/2 and HIV-1, n = 35 | Mortality: 12/35 (34.3%) vs. 3/39 (7.7%), p = 0.01 Opportunistic: 88.6 vs. 44.7%, p = <0.001. –Shorter survival for coinfected patients, p = 0.003 |
The CD4+ cell count was higher in coinfected than in monoinfected patients: 1,429 ± 608 vs. 928 ± 768, p = 0.003. –Any clinical symptoms were described more frequently on coinfected (64.6%) than monoinfected patients (35.4%), OR: 9.6, 95% CI: (2.8–32.5). |
| Brites (24) | Retrospective, cross- sectional, Brazil | Total n = 123 Male: 97 (78.9%) Age: m = 33.4 (± 8.1) | HTLV-1/2 and HIV-1 n = 26 | Strongyloidiasis: 4/26 (15.4%) vs. 2/97 (2.1%), [OR = 8.55; 95% CI: (1.21–73.62)], p = 0.02. | 2 cases of encephalopathy were diagnosed in coinfected, vs. no case detected on monoinfected patients, p = 0.04. Coinfected patients were less frequently on ART use than monoinfected ones, (42.3 vs. 64.3%, p = 0.04). |
| Mendoza (25) | Cross- sectional, Spain | Total n = 369 Female: 227 (63.6%) Age: m = 50 | HTLV-1 and HIV-1, n = 12 | AIDS progression: 7/12(58%) vs. 10/357(2.8%). HAM/TSP: 2/12 (16%) vs. 46/357. (12.8%). |
Frequency of clinical manifestations in coinfected patients was significantly higher than in monoinfected ones. The AIDS conditions reported on HTLV monoinfected patients were recurrent pneumonia, extrapulmonary tuberculosis, and esophageal candidiasis. Late diagnosis explains the high rate (9/12) of clinical manifestations in the HIV-HTLV co-infected population. |
| Brites (26) | Nested Retrospective Case-control, Brazil | Total n = 298 Female: 166 (59.1%) Age: m = 39.0 (±9.1) | HTLV-1 and HIV-1, n = 149 | Survival: 16.7(±0.7) years vs. 18.1(±4) years, p = 0.001. Deaths: 53 (17.8%) vs. 23 (7.7%). Mortality rate 2.1 per 100 persons-year. - ART use: all participants (100%). |
Shorter survival for coinfected patients with detectable pVL compared to those with undetectable viremia: ≥ 50 copies/mL: 8.4 ± 0.8 vs. 12.9 ± 1.4 years, p = 0.02 >1,000 copies/mL: 6.7 ± 0.9 vs. 11.0 ± 0.1 years, p = 0.04 Survival time did not differ for patients monoinfected (19.0 ± 0.4 years) vs. coinfected (20.2 ± 0.6 years) presenting with pVL <50 copies/mL (P = 0.5). Deaths were largely caused by AIDS-related conditions, and frequency of causes of death was similar across groups. Successful ART is able to normalize survival. |
HIV, Human Immunodeficiency Virus; HTLV, Human T-cell lymphotropic Virus; AIDS, Acquired Immunodeficiency Syndrome; WHO, World Health Organization; HAM/TSP, Human T-lymphotropic virus type-I-associated myelopathy / tropical spastic paraparesis; ART, Antiretroviral Therapy; PN, Peripheral Neuropathy; pVL, Plasma Viral Load; HR, Hazard Ratio.