Sir,
CD4+ cell count is a reliable predictor of the risk of disease and death among HIV-infected individuals. CD4+ cell count below 100 cells/μl multiple times despite antiretroviral therapy (ART) is considered immunological failure to ART.[1] A 6-month time period after initiation of ART regimen is considered sufficient to lift CD4+ cell count to normal levels.[2] Recognizing the significance of such cases, we analyzed data of HIV-infected individuals who reported two or more CD4+ cell count below 100/μl after >6 months of first-line ART during 2009–2018 (10-year study group). COVID-19 period was excluded as it disrupted HIV testing and was associated with reduced CD4+ cell count.[3,4]
12.3% of ART-treated HIV-positive individuals reported two or more CD4+ cell count <100 cells/μl after >6 months of first-line ART. Such cases have gradually increased since 2012. Compared with control group (i.e., individuals with last CD+ Cell count >500 cells/μl after >6 months of first-line ART during the same period), there were significantly higher proportionate of individuals in age groups 30–40 years, 40–50 years, 50–60 years, and >60 years in study group (P < 0.0001, >30 years vs. <30 years; Chi-square test) [Table 1]. There were significantly higher numbers of males and lower females in study group than control group (P < 0.0001; Chi-square test). There was significantly higher percentage of individuals with monthly income below Indian rupee (INR) 10,000 in study group in comparison to control group (P = 0.05, INR <10,000 vs. INR >10,000; Chi-square test). Study group had 7.5 times more individuals with baseline (i.e., at the time of HIV confirmation) CD4+ cell count <100 cells/μl (P < 0.0001; Chi-square test) and nine times less individuals with baseline CD4+ cell count >500 cells/μl (P < 0.0001; Chi-square test) than control group. Only 9.7% of individuals in study group could reach last CD4+ count >500 cells/μl, 37.5% had last known CD4+ count >200 cells/μl, 19.1% had last known CD4+ count 100–200 cells/μl, and 43.0% reported last known CD4+ count <100 cells/μl. There was nonsignificant difference in the existence of tuberculosis in study group and control group (P = 0.21, HIV-TB vs. Non-HIV-TB; Chi-square test); although study group had higher tuberculosis incidence than control group (7.2% vs. 5.4%) [Table 1]. The death rate in study group was 14.9% and it was significantly higher in comparison to control group (1.4%) (P < 0.0001, died vs. alive; Chi-square test) [Table 1]. Among those who died in the study group, only 1.7% had CD4+ cell count >500 cells/μl at the time of HIV confirmation.
Table 1.
Factors associated with CD4+ cell count <100 cells/μl on multiple occasions after >6 months first-line antiretroviral therapy treatment (study group), the control group included those with current CD4+ cell count >500 cells/μl after >6 months of first-line antiretroviral therapy treatment
| Factors | Study group (n=387) | Control group (n=1936) |
|---|---|---|
| Age at confirmation of HIV infection (years) | ||
| <5 | 0 | 68 (3.5) |
| 5-15 | 15 (3.8) | 137 (7.0) |
| 15–30 | 102 (26.3) | 750 (38.7) |
| 30–40 | 154 (39.8) | 615 (31.7) |
| 40–50 | 79 (20.4) | 241 (12.4) |
| 50–60 | 28 (7.2) | 96 (4.9) |
| >60 | 9 (2.3) | 29 (1.5) |
| Sex | ||
| Male | 299 (77.2) | 1115 (57.5) |
| Female | 87 (22.5) | 816 (42.1) |
| Transgender | 1 (0.2) | 5 (0.2) |
| Education | ||
| Illiterate | 35 (9.0) | 216 (11.1) |
| Primary | 301 (77.7) | 1396 (72.1) |
| Secondary | 32 (8.2) | 186 (9.6) |
| Higher | 19 (4.9) | 138 (7.1) |
| Monthly income (INR) | ||
| <10,000 | 282 (73) | 1310 (67.8) |
| 10,000–20,000 | 70 (18.1) | 446 (23.1) |
| >20,000 | 34 (8.8) | 174 (9.0) |
| Mode of infection | ||
| Heterosexual | 344 (88.8) | 1575 (78.8) |
| Mother to child | 21 (5.4) | 260 (13.4) |
| Blood transfusion | 1 (0.2) | 15 (0.77) |
| Men to men sex | 2 (0.5) | 14 (0.72) |
| Unsafe injection | 5 (1.2) | 19 (0.9) |
| Unknown | 14 (3.6) | 52 (2.6) |
| Baseline CD4+ cell count (cells/μl) | ||
| <100 | 210 (54.2) | 143 (7.3) |
| 100–200 | 94 (24.2) | 198 (10.2) |
| 200–350 | 47 (12.1) | 515 (26.6) |
| 350–500 | 14 (3.6) | 443 (22.8) |
| >500 | 14 (3.6) | 634 (32.7) |
| Unavailable | 8 (2.0) | 3 (0.1) |
| ART adherence | ||
| >95% | 197 (50.9) | 580 (29.9) |
| 80%–95% | 53 (13.6) | 212 (10.9) |
| <80% | 14 (3.6) | 71 (3.6) |
| Unavailable | 123 (31.7) | 1073 (55.4) |
| Tuberculosis | ||
| HIV-TB | 28 (7.2) | 106 (5.4) |
| Non-HIV-TB | 359 (92.7) | 1830 (94.5) |
| IPT | 37 (9.5) | 150 (7.7) |
| Non-IPT | 350 (90.4) | 1786 (92.2) |
| Fatality | ||
| Died | 58 (14.9) | 29 (1.4) |
| Alive on ART | 171 (44.1) | 716 (36.9) |
| Transfer out | 118 (30.4) | 60 (3.1) |
| LFU | 40 (10.3) | 1131 (58.4) |
HIV=Human immunodeficiency virus; INR=International normalized ratio; ART=Antiretroviral therapy; TB=Tuberculosis; IPT=Isoniazid Preventive Therapy; LFU=Lost to follow up
CD4+ cell count at the time of HIV confirmation is the strongest predictor of recovery in CD4+ counts following initiation of ART.[5] Starting ART at CD4+ cell count >500 cells/μl and within 4 months of HIV seroconversion is associated with a greater long-term increase in CD4+ count.[5] ART is now initiated as soon as HIV infection is diagnosed, however, late diagnosis of HIV infection complicates CD4+ cells recovery. Awareness campaigns regarding “health hazards in late ART initiation” are needed to motivate people for early HIV testing and ART initiation at healthy baseline CD4+ cell count.
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Conflicts of interest
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References
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