Recurrent tuberculosis among HIV co-infected patients: A Case Series from KwaZulu-Natal

Figures & data

Table 1 Epidemiologic and clinical characteristics of five patients with recurrent (M) XDR-TB following drug-susceptible TB

Clinical and epidemiologic biomarker	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Age	38	32	38	36	30
Gender	M	M	F	F	F
BMI
BMI at TB-1 diagnosis	19.4	18.7	17.6	21.4	26
BMI at TB-1 end	18.4	20.5	18.7	23.2	26.5
BMI at TB-2 diagnosis	21.3	20.4	17.0	19.4	25.8
Initial episode of TB
Date and method of diagnosis	Jul 2007	Jul 2007	Jan 2007	Nov 2007	Aug 2005
	X-ray + sputum	X-ray + sputum	X-ray + sputum	X-ray + sputum	X-ray + sputum
Genetic and susceptibility	Beijing	F15/LAM4/KZN	F28	F28	Unique
profile	DS-TB	Ds-TBLymph aspirate resistant to INH and RIF	Ds-TB	Ds-TB	Ds-TB
Chest radiograph	Infiltrates on	Infiltrates on RL	cavities,	cavities and	cavities and
	RL; cavities and infiltrates on LL	and LL	infiltrates, pleural disease, and shrinkage and destruction in RL, minimal fibrosis on LL	infiltrates in RL and LL	infiltrates in RL and LL
Completion date, duration on	1 april 2008	20 March 2008	20 August 2007	Jun 30 2008	02 January 06
treatment and outcome	8 months	8 months	10 months	7 months	6 months
	cure	cure	cure	cure	cure
Chest radiograph at the end of treatment	Fibrosis in upper RL	Fibrosis in LL	Extensive fibrosis	Not available	Not available
Recurrent MDR/XDR episode of TB
Mechanism of recurrence,	Reinfection	Relapse	Reinfection	Relapse	Relapse
Genetic profile of TB isolates	Beijing to KZN	KZN strain	F28 - unique	F28 strain	Unique strain
and time to recurrence	strain 24 months	28 months	19 months	28 months	15 months
Date and method of diagnosis	June 10	Feb 2011	Apr 2010	Nov 2010	May 07
	X-ray + sputum culture	X-ray + sputum	X-ray + sputum culture	X-ray + sputum	X-ray + sputum
Susceptibility profile	XDR-TB	MDR-TB	MDR-TB	MDR-TB	XDR-TB
	Resistant to	Resistant to INH,	Resistant to NH,	Resistant to INH,	INH, RIF, EMB,
	INH, RIF, EMB,	RIF, EMB, ETH,	RIF, ETH, sM,	EMB, RIF, SM, ETH,	MXF, KANA,
	kanamycin, capreomycin, OFX, Ialiamide, sM, ETH, and PZA	PZA, and sM	and PZA	and PZA	and ETH
Radiologic findings	Infiltrates on RL and infiltrates and new lesions on LL	cavities in LL	Bullae and plural effusion in RL	cavities and infiltrates on RL and fibrosis on LL	cavitation in LL
Treatment outcome	Transferred out for DR-TB care	Transferred out for DR-TB care	Died	Withdrew from study	Transferred out for DR-TB care
HIV history
Date of diagnosis	Jul 2007	Jul 2007	Jan 2007	Dec 2007	2005
Treatment regimen	AZT/3Tc/EFV, switched AZT to TDF in May 2009	ddI/3Tc/EFV (discontinued between March and April 2009)	ddI/3Tc/EFV	ddI/3Tc/EFV switched to ABc/ TDF/LPV/r in October 2008, and back to regimen 1 in June 2011	ddI/3Tc/EFV, switched to TDF in July 2011
Regimen response	Virologic	Raised CD4 count	Good virologic	Failed both	Good virologic
	suppression;	and virologic	suppression,	regimens, placed	suppression,
	sustained high	suppression by	CD4 cell count	back onto Regimen	CD4 count
	CD4+ cell count	Month 12	remained low	I	remained low
CD4/VL at initial TB diagnosis	CD4 =200	CD4 =54	CD4 =151	CD4 =245	CD4 =205
	VL =260,000	VL =126,000	VL =41,663	VL = Unavailable	VL =83,900
CD4/VL at the end of first TB	CD4 =434	CD4 =377	CD4 =331	CD4 =212	CD4 =352
episode	VL =400	VL ≤400	VL ≤400	VL =27,400	VL ≤400
CD4/VL at recurrent TB	CD4 =3,652	CD4 =565	CD4 =245	CD4 =143	CD4 =204
diagnosis	VL = unavailable	V ≤400	VL ≤40	VL =20,302	VL =69,400
Other notes
TB risk profile	Hospitalization	Hospitalization	Hospitalization	Household TB contacts	No risks
Adherence profile	Poor; adherence support program	Fair; missed clinic visits due to alcohol use, occasional missing of doses	Good	Poor;hospitalization for supervised TB treatment	Good
Other medical conditions	Anemia, PN, SN, HepB	IRIS on TB treatment, PN	PN, pneumonia in August 2010	Hypertension, PN	None
Substance use history	Alcohol abuse, smoking	Alcohol abuse, smoking	None	None	None

Notes: Initial episode of TB = TB-1; Recurrent episode of TB = TB-2 radiological findings from chest x-rays conducted after diagnosis and treatment end (closest date available given).

Abbreviations: 3TC, lamivudine; ABC, abacavir; ALV, alluvia; AZT, azidothymidine; BMI, body mass index; CD4, CD4+ T-cell count (cells/µL³); DDI, didanosine; EFV, efavirenz; EMB, ethambutol; ETH, ethionamide; Hep B, hepatitis B; INH, isoniazid; LL, left lung; MDR, multi-drug-resistant; OFX, ofloxacin; PN, peripheral neuropathy; PTB, pulmonary TB; PZA, pyrazinamide; R4, Rifafour; RIF, rifampicin; RL, right lung; SM, streptomycin; SN, sensory neuropathy; TB, tuberculosis; TDF, tenofovir; VL, viral load (copies/µL³); XDR, extensively drug-resistant.

Table 2 HIV drug resistance profiles at TRUTH study entry and exit visits

	ART regimen	Drug resistance mutations at TRUTH entry	Drug resistance mutations at the end of TRUTH study
Patient 1	AZT/3TC/EFV switched to TDF/3TC/EFV	NRTI: D67N; K70R; MI84V; T215I^a; K2I9E	NRTI: MI84V
		NNRTI: VI06M; Y188P^b; M230L	NNRTI: KI03N; GI90A; YI88L
Patient 2	ddI/3TC/EFV	None	NRTI: MI84V
			NNRTI: VI06M; YI88L
Patient 3	ddI/3TC/EFV	NRTI: T2l5S^b	NRTI: K70E; MI84V
		NNRTI: KI03N	NNRTI: KI03N
Patient 4	ddI/3TC/EFV switched to ABC/TDF/	None	NRTI: MI84V
	LPV/r then switched back to ddI/3TC/EFV		NNRTI: KI0IE; KI03N; GI90A
Patient 5	ddI/3TC/EFV switched to TDF/3TC/EFV	None	NRTI: MI84I
			NNRTI: VI06M; YI88C; H22IY

Notes: ^aRevertant mutation;

b Transitional mutation. None of the patients had any resistance associated mutation prior to the initiation of treatment.

Abbreviations: 3TC, lamivudine; ABC, abacavir; ddI, didanosine; AZT, zidovudine; EFV, efavirenz; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; LPV/r, lopinavir-boosted ritonavir (Aluvia; Abbott, South Africa).

Figure S1 Chest X-rays of Patient 1 depicting (A) infiltrates on both lungs; (B) persistent fibrosis in the left lung; and (C) cavities in the left lung.

Figure S2 Chest X-rays of Patient 2 depicting (A) infiltrates in both lungs and cavities in the left lung; (B) right upper lobe fibrosis; and (C) infiltrates in the right lung and infiltrates and new lesions in the left lung.

Figure S3 Chest X-rays of Patient 3 depicting (A) cavities and infiltrates in both lungs; (B) cavities and infiltrates on the right lung and fibrosis in the left lung; and (C) cavities, infiltrates, and patchy consolidation in the right lung and consolidation in mid and lower zones of the left lung.

Figure S4 Chest X-rays of Patient 4 depicting (A) vast damage to the right lung with cavities, infiltrates, pleural disease, shrinkage, and destruction. Minimal damage to the left lung; (B) residual widespread damage to the right lung; and (C) right lung bullae and new pleural effusion. New infiltrates in left lung.